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Biomedical subjects

Yasuo Yoshioka

Publications and source records attributed to Yasuo Yoshioka.

At least 19 recordsLinked to original sources
PubMed2007

Novel correction methods as alternatives for the six-dimensional correction in CyberKnife treatment.

PURPOSE: During CyberKnife treatment, the 6D correction method is used to correct patient positional errors, including rotational ones. We developed novel correction methods for translating rotational errors into 3D, with the aim of making their correction safer than with 6D correction and as accurate as possible. MATERIALS AND METHODS: These novel correction methods were named the gravity correction and the beam correction method. With the gravity correction method, the beam coordinates after rotation are corrected to match the tumor gravity point with 3D translational components translated by the affine transformation matrix. For beam correction, the beam coordinates are corrected to match the translated tumor target coordinates for each treatment beam. The effectiveness and impact of these methods were demonstrated by means of dose volume histogram (DVH) shift evaluation. For analysis of the treatment data of 10 patients, the treatment beam was rotated in three patterns of rotational degree and corrected with the two methods. The amount of tumor gravity point shift in the rotation was also calculated, and the deterioration of the tumor DVH was studied. RESULTS: In the case of +/-1 degrees , +/-3 degrees , and +/-1 degrees rotation for the X, Y, Z axes, the tumor gravity point of all 10 patients moved around 2.4 mm on average. Tumor DVH was deteriorated worse as the distance between the tumor gravity point and the rotational origin became more distant. With the planned D90, which represents the dose above which 90% of the tumor volume is irradiated set at 100%, the postrotational average D90 dose deteriorated to 96.12% after (+/-1 degrees , +/-3 degrees , and +/-1 degrees ) rotation. The dose was improved to 99.9% (SD +/- 0.41) after the gravity correction, or to 99.87% (SD +/- 0.55) after the beam correction. CONCLUSION: The correction methods developed by us can correct tumor DVH findings to the same degree as with 6D correction and are safer because the movement required for correcting the linac is not rotational but translational only.

Head and Neck Neoplasms↗
PubMed2006

A strategy for efficient cross-presentation of CTL-epitope peptides leading to enhanced induction of in vivo tumor immunity.

The activation of antitumor cytotoxic T-lymphocytes (CTLs) depends on how efficiently the relevant tumor antigen peptides are delivered into the major histocompatibility complex (MHC) class I presentation pathway in antigen presenting cells (APCs). An elegant approach to promote the peptide-MHC class I association has been described for enhanced peptide transportation into the endoplasmic reticulum (ER) by adding an ER insertion signal sequence (Eriss). Nevertheless, this approach does not appear potent enough to induce in vivo tumor protective immunity. Herein, we present a novel peptide-vaccine strategy based on the combined utilization of Eriss and fusogenic liposomes (FLs) capable of directly introducing encapsulated CTL-epitope peptides into the MHC class I pathway of APCs. APCs pulsed with free peptides, FL-encapsulated peptides, or FL-encapsulated Eriss-conjugated peptides exhibited comparable levels of antigen-presenting activity at early phases after pulsing. Interestingly, whereas in the first two methods the APC ability began to decline 40 to 60 h after pulsing, FL-encapsulated Eriss(+) peptides allowed APCs to retain peptide-presentation activity for at least 140 h. This advantage of FL-encapsulated Eriss(+) peptides correlated with the induction of more potent antitumor immunity compared with soluble Eriss(+) or Eriss(-) peptides or FL-encapsulated Eriss(-) peptides when they were administered in vivo. Thus, Eriss-conjugated CTL-epitope peptides encapsulated in FLs provide a highly efficient tumor-vaccine to enhance the induction of in vivo tumor immunity.

Amino Acid Sequence↗
PubMed2006

High-dose-rate brachytherapy without external beam irradiation for locally advanced prostate cancer.

BACKGROUND AND PURPOSE: High-dose-rate brachytherapy (HDR-BT) had been used only in combination with external beam irradiation (EBI) until our previously reported first trial of HDR-BT alone without EBI. The purpose of the current report is to evaluate the feasibility, toxicity and efficacy of this regimen, with more patient accrual and longer follow-up. MATERIAL AND METHODS: From 1995 through 2004, 111 patients with localized prostate cancer were treated with HDR-BT without EBI. Fifteen patients were considered as low-risk, 28 as intermediate-risk, and 68 as high-risk. The prescribed dose was 48 Gy/8 fractions/5 days or 54 Gy/9 fractions/5 days. Median follow-up time was 27 months (range 5-119). RESULTS: All the patients completed the treatment regimen. The 3- and 5-year PSA failure-free rates were 83% and 70%, and the local control rates 100% and 97%. The maximum toxicities observed were Grade 3 by CTCAE v3.0 (6 acute, 1 chronic). CONCLUSIONS: HDR-BT without EBI was feasible and its toxicity acceptable. Short-term tumor control was promising, even for locally advanced cases. More patient accrual and longer follow-up are needed to confirm the efficacy of this novel approach.

Aged↗
PubMed2006

Chondroitin sulfate intake inhibits the IgE-mediated allergic response by down-regulating Th2 responses in mice.

Chondroitin sulfate (CS) was administered orally to BALB/c mice immunized intraperitoneally with ovalbumin (OVA) and/or dinitrophenylated OVA. The titers of antigen-specific IgE and IgG1 in mouse sera were determined. The antigen-specific IgE production by mice fed ad libitum with CS was significantly inhibited. We also examined the effect of feeding CS on immediate-type hypersensitivity. One hour after antigen stimulation, the ears of mice fed with CS swelled less than those of the control mice. Furthermore, the rise in serum histamine in the mice fed with CS under active systemic anaphylaxis was significantly lower than that in the controls. We next examined the pattern of cytokine production by splenocytes from mice followed by re-stimulation with OVA in vitro. The splenocytes from the mice fed with CS produced less interleukin (IL)-5, IL-10, and IL-13 than those from the control group. In contrast, the production of interferon-gamma and IL-2 by the splenocytes of mice fed with CS was not significantly different from those in the control mice. In addition, the production of transforming growth factor-beta from the splenocytes of mice fed with CS was significantly higher than that of the control mice. Furthermore, we showed that the percentages of CD4(+) cells, CD8(+) cells, and CD4(+)CD25(+) cells in the splenocytes of mice fed with CS are significantly higher than those of the control. These findings suggest that oral intake of CS inhibits the specific IgE production and antigen-induced anaphylactic response by up-regulating regulatory T-cell differentiation, followed by down-regulating the Th2 response.

Administration, Oral↗
PubMed2006

Profile analysis and immunoglobulin E reactivity of wheat protein hydrolysates.

BACKGROUND: Wheat protein hydrolysates have been traditionally used as food additives and are now being used in cooking worldwide. There have been a few studies on the relationship between the molecular mass distribution and the immunoglobulin E (IgE) reactivity of the wheat protein hydrolysates. METHOD: We analyzed the peptide profile of commercial wheat protein hydrolysate samples from enzymatic or acid hydrolysis of wheat protein using size exclusion chromatography. We further investigated the IgE reactivity of the wheat protein hydrolysates using the inhibition ELISA method and sera of 5 patients sensitive to wheat. RESULTS: The wheat protein enzymatic hydrolysate samples showed high concentrations of peptides with molecular masses greater than 1,050 Da, whereas in contrast, the wheat protein acid hydrolysates showed extremely low concentrations of peptides with molecular masses greater than 1,050 Da. Tested wheat protein acid hydrolysates hardly inhibited the patient IgE binding ability to wheat proteins in the five patient sera. On the contrary, some tested wheat protein enzymatic hydrolysate samples inhibited the IgE binding ability to wheat proteins. CONCLUSION: These results suggested that the uptake of wheat protein enzymatic hydrolysates might still have the possibility of causing food allergic reactions in patients allergic to wheat and the processed foods containing them.

Binding Sites, Antibody↗
PubMed2006

High-dose-rate brachytherapy combined with long-term hormonal therapy for high-risk prostate cancer: results of a retrospective analysis.

PURPOSE: High-dose-rate (HDR) brachytherapy combined with hormonal therapy (HTx), without the addition of external beam radiation therapy (EBRT) for high-risk prostate cancer was evaluated retrospectively. MATERIALS AND METHODS: Between May 1995 and April 2002, 35 patients with prostate cancer [Stage > or = T2b (UICC 1997) or tumor grading=3 or prostate-specific antigen (PSA) level > or = 20 ng/mL] were treated with HDR brachytherapy combined with HTx. Most patients (74%) had two or more of these factors. All patients received Iridium-192 HDR brachytherapy with a total dose of 54 Gy/9 fractions/5 days (48 Gy/8 fractions/5 days for the first 6 cases) in one implant session. The median neoadjuvant HTx [luteinizing hormone-releasing hormone (LH-RH) agonist and antiandrogen] period was 7 months. The median adjuvant HTx (ATH) (LH-RH agonist) period was 40 months, and median follow-up was 57 months (range, 23-117 months). RESULTS: The 5-year actuarial biochemical control, local control, and disease-free rates were 62%, 96%, and 76% respectively. No patients experienced local and/or regional relapse without distant progression. The 5-year actuarial cause-specific survival and overall survival rates were 89% and 87%, respectively. The acute and late toxicity were moderate and well tolerated. CONCLUSION: HDR brachytherapy plus long-term HTx is at least as effective as conventional EBRT plus long-term HTx.

Aged↗
PubMed2006

New ambulatory implant technique of high-dose-rate interstitial brachytherapy for prostate cancer.

PURPOSE: The aim of this study was to improve the performance status of prostate cancer patients during high-dose-rate interstitial brachytherapy (HDR-ISBT). To this end, we have developed a new ambulatory implant technique. MATERIALS AND METHODS: Ten prostate cancer patients were treated with HDR-ISBT as monotherapy from October 2003 until March 2004. We utilized a new removable template, a flexible applicator with a nonmetallic bead and button stopper, and an inner catheter connecting the applicator and the transfer tube of the brachytherapy unit. We shortened the connector end of the flexible applicator to enable the patient to sit down and walk freely during the treatment time. RESULTS: All 10 patients could walk without any support. No problem in the application was observed. CONCLUSION: Our new ambulatory implant technique for HDR-ISBT was able to improve the performance status of prostate cancer patients.

Aged↗
PubMed2006

[A case of effective chemoradiation therapy against anal fistula carcinoma recurred 10 years after surgery].

A male in his eighties underwent abdominoperineal resection under the diagnosis of adenocarcinoma associated with anal fistula (P0, H0, n (-), A1, stage II, ly0, v0). Ten years after the surgery, a painful lymph node swelling was noticed in the left inguinal region. Biopsy specimen showed adenocarcinoma consisting of severe dysplastic cells. Radiotherapy was performed in the pelvic region at a total dose of 50 Gy (2 Gy/day). After the radiotherapy, left inguinal and pelvic lymph nodes markedly shrank and became painless. After one month, the chemotherapy with UFT (UFT 300 mg/day) was started. One year thereafter, para-aortic lymph nodes were found to be enlarged, but a good quality of life was obtained without elevation of tumor markers.

Adenocarcinoma↗
PubMed2005

Optimization of dose distribution for HDR brachytherapy of the prostate using Attraction-Repulsion Model.

PURPOSE: To optimize dose distribution for high-dose-rate brachytherapy for prostate cancer, we have developed a new algorithm named Attraction-Repulsion Model (ARM). In this study, we compared the ARM with geometric optimization (GO). METHODS AND MATERIALS: The ARM was used to optimize the dose distribution by finding the best dwell time combination. ARM requires grids inside the clinical target volume (CTV) and critical organs. These grids generate attraction or repulsion based on specific dose constraints. After calculations were performed repeatedly until the attraction and repulsion forces reached equilibrium, the optimal dwell time distribution was established. We compared the ARM with GO for 10 patients using dose-volume histograms. RESULTS: The CTV ranged from 23 to 48 cc, and the CTV V150 ranged from 52% to 79%, and 23% to 44% for GO and ARM, respectively. This indicates that the dose homogeneity indices, as well as the conformal indices, were higher for ARM than for GO. The urethra V150 was 0-99% and 0-1% for GO and ARM, respectively. CONCLUSION: The ARM proved to be superior to GO in minimizing the dose to normal structures and in improving dose homogeneity for the target while reducing the dose to normal tissues.

Algorithms↗
PubMed2005

Dietary unripe apple polyphenol inhibits the development of food allergies in murine models.

The incidence of type I allergic disorders has been increasing worldwide, particularly, the hypersensitivity to food. We first showed that apple condensed tannin (ACT) intake would inhibit the development of the oral sensitization and that the inhibition could correlate with the rise in the population of TCR(gamma)delta-T cells in the intestinal intraepithelial lymphocytes (IEL) using W/W(V) mice and B10A mice which were ovalbumin (OVA)-orally sensitized. Serum OVA-specific immunoglobulin E and immunoglobulin G1 titers in the OVA-orally sensitized W/W(V) and B10A mice ad libitium fed ACT were extremely inhibited compared to those of the control. The ACT intakes of OVA-sensitized W/W(V) and B10A mice inhibited the immediate reduction of the body temperature or the rise in serum histamine induced by active systemic anaphylaxis. The proportions of the TCR(gamma)delta-T cells in the IEL of the OVA-orally sensitized W/W(V) and B10A mice ad libitium fed ACT were significantly greater than that in the controls. Furthermore, ACT feeding by itself could induce the rise in the percentage of the TCR(gamma)delta-T cells among the IEL of the W/W(V) and B10A mice. This suggests that the ACT intake may prevent the development of food allergies and this effect could be correlated with the rise in the percentage of TCR(gamma)delta-T cells among the IEL.

Allergens↗
PubMed2005

Evaluation of anatomy-based dwell position and inverse optimization in high-dose-rate brachytherapy of prostate cancer: a dosimetric comparison to a conventional cylindrical dwell position, geometric optimization, and dose-point optimization.

BACKGROUND AND PURPOSE: To compare treatment planning methods in high-dose-rate (HDR) brachytherapy of prostate cancer. In particular, to assess quantitatively the dosimetric superiority, if any, of the anatomy-based dwell position (ABDP) and inverse optimization (IO) over the conventional cylindrical dwell position (CDP), geometric optimization (GO), and dose-point optimization (DO) in terms of the determination of dwell positions and dwell times. PATIENTS AND METHODS: Between September 2002 and April 2003, 10 cases of treatment-planning CT images were taken for external radiotherapy for prostate cancer. Treatment planning computer software and the CT data were used to create hypothetical HDR brachytherapy applicator needles, which were properly implanted in the prostate. Six different plans including IO with ABDP (IO(ABDP)), IO with CDP (IO(CDP)), GO with ABDP (GO(ABDP)), GO with CDP (GO(CDP)), DO with ABDP (DO(ABDP)), and DO with CDP (DO(CDP)) were made for each case, that is, 60 plans in total. All plans were normalized so that the D(95) should be equal to 100% of the prescribed dose. Dose-volume histograms from all 60 plans were analyzed, and multiple implant quality indices, including CI, EI, DNR, %V(R 75), %V(B 75), and %V(U 150) for each plan, were extracted and compared. Then, the best settings for IO(ABDP) regarding dwell position and dose limit were sought for. RESULTS: ABDP showed a statistically significantly lower EI (P<0.001), %V(R 75) (P=0.002), and %V(B 75) (P=0.015) than CDP. IO showed a statistically significantly lower %V(U 150) than GO (P=0.009), or than DO (P<0.001). Given a definition that a figure exceeding three-fold of the minimum figure of the index is clinically unacceptable, only in IO(ABDP) all index figures were clinically acceptable, while in the other five plans at least one index figure was unacceptable. CONCLUSIONS: In the CT-based treatment planning for prostate HDR brachytherapy, ABDP is useful to achieve a high conformity, which leads to a reduction of the doses to the bladder, rectum, and surrounding normal tissue. IO is useful to lower the urethral dose without sacrificing conformity. IO(ABDP) is recommended on the basis of the current study. However, this conclusion has been drawn from the idealized hypothetical settings, and some possibility remains that this conclusion is not always applicable to the real implants.

Brachytherapy↗
PubMed2005

Phage display and PEGylation of therapeutic proteins.

With the success of the human genome project, the focus of life science research has shifted to the functional and structural analyses of proteins, such as disease proteomics and structural genomics. These novel approaches to the analyses of proteins, including newly identified ones, are expected to help in the identification and development of protein therapies for various diseases. Thus, disease proteomic-based drug discovery has a very high profile. Nevertheless, the use of bioactive proteins in the clinical setting is not straightforward because, in vivo, these proteins have a low stability and a pleiotropic action. To promote disease proteomic-based drug discovery and development, we have attempted to establish a system for creating functional mutant proteins (muteins) with the desired properties, and also to develop a site-specific polymer-conjugation system for further improving their therapeutic potency. These innovative protein-drug systems are discussed in this review.

Animals↗
PubMed2005

Urinary 8-hydroxy-2'-deoxyguanosine excretion as a biomarker for estimating DNA oxidation in patients undergoing external radiotherapy and/or brachytherapy.

Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) is considered to be a biomarker of cellular oxidative stress and to be associated with carcinogenesis. To estimate the oxidative stress caused by radiotherapy, we used the enzyme-linked immunosorbent assay (ELISA) to monitor urinary 8-OHdG levels in 72 patients undergoing radiotherapy. Subjects consisted of 23 breast cancer patients undergoing post-operative external radiotherapy for breast conserving therapy, 12 tongue and seven prostate cancer patients undergoing interstitial radiotherapy, 19 esophageal cancer patients undergoing external radiotherapy and chemotherapy, and 11 cervical cancer patients undergoing external radiotherapy and brachytherapy with or without chemotherapy. Before radiotherapy, cervical cancer patients showed a higher urinary 8-OHdG level (16.0+/-8.8 ng/mg) than breast cancer patients (5.3+/-5.5 ng/mg, p=0.001). In the other three groups, urinary 8-OHdG levels were in the medium range (prostate cancer patients: 6.6+/-6.3 ng/mg; esophageal cancer patients: 8.8+/-11.1 ng/mg; tongue cancer patients: 10.2+/-6.7 ng/mg). Radiotherapy did not cause changes in the excretion level of urinary 8-OHdG in patients with breast, esophageal and tongue cancer. However, radiotherapy reduced 8-OHdG excretion levels in patients with cervical cancer, whereas interstitial radiotherapy transiently increased these levels in patients with prostate cancer.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2004

Functionalization of tumor necrosis factor-alpha using phage display technique and PEGylation improves its antitumor therapeutic window.

PURPOSE: In this study, the optimization of antitumor therapy with tumor necrosis factor-alpha (TNF-alpha) was attempted. EXPERIMENTAL DESIGN: Using the phage display technique, we created a lysine-deficient mutant TNF-alpha (mTNF-K90R). This mutant had higher affinities to both TNF receptors, despite reports that certain lysine residues play important roles in trimer formation and receptor binding. RESULTS: The mTNF-K90R showed an in vivo therapeutic window that was 13-fold higher than that of the wild-type TNF-alpha (wTNF-alpha). This was due to the synergistic effect of its 6-fold stronger in vitro bioactivity and its 2-fold longer plasma half-life derived from its surface negative potential. The reason why the mTNF-K90R showed a higher bioactivity was understood by a molecular modeling analysis of the complex between the wTNF-alpha and TNF receptor-I. The mTNF-K90R, which was site-specifically mono-PEGylated at the NH2 terminus (sp-PEG-mTNF-K90R), had a higher in vitro bioactivity and considerably longer plasma half-life than the wTNF-alpha, whereas the randomly mono-PEGylated wTNF-alpha had 6% of the bioactivity of the wTNF-alpha. With regard to effectiveness and safety, the in vivo antitumor therapeutic window of the sp-PEG-mTNF-K90R was 60-fold wider than that of the wTNF-alpha. CONCLUSIONS: These results indicated that this functionalized TNF-alpha may be useful not only as an antitumor agent but also as a selective enhancer of vascular permeability in tumors for improving antitumor chemotherapy.

Animals↗
PubMed2004

Optimal construction of non-immune scFv phage display libraries from mouse bone marrow and spleen established to select specific scFvs efficiently binding to antigen.

Monoclonal antibodies (MAbs) are widely applied in basic research, medicine, and the pharmaceutical industry. Recently, applications and generations of MAbs have been increasingly attracting attention in many research areas since MAbs could be produced in large quantities with the development of genetic technology and antibody engineering. On the other hand, in recent years, phage display system has been developed for high-throughput isolation and generation of novel MAbs that have high affinity with various antigens. This technology is capable of constructing "Library" containing billions of phage repertoires displaying various antibody fragments, and rapid selection of a specific MAb from this phage library. Additionally, this technology has a great advantage that MAbs can be generated without immunization to animals. However, there are still relatively few reports confirming that useful MAbs can be derived from non-immune antibody libraries. The latter, as undertaken by current methods, seem unable to achieve the high quality required to produce useful MAbs for any desired antigen because cloning of antibody gene from non-immune donors is inefficient. This problem is caused by the fact that their RT-PCR primer sets, PCR conditions, and efficiency of subcloning through construction of antibody gene library cannot encompass all the antibody diversity. In an attempt to overcome some of these earlier problems, here we describe an optimized method to establish a high quality, non-immune library from mouse bone-marrow and spleen, and assess its diversity in terms of content of multiple antibodies for a wide antigenic repertoire. As an example of the application of the methodology, we describe the selection of specific MAbs binding to Luciferase and identify at least 18 different clones. Using this non-immune mouse antibody library, we also obtained MAbs for VEGF, VEGF receptor 2, TNF-alpha, and Pseudomonas Exotoxin, confirming the high quality of the library and its suitability for this application.

Animals↗
PubMed2004

Effective accumulation of poly(vinylpyrrolidone-co-vinyl laurate) into the spleen.

To optimize polymer-conjugated drugs as a polymeric drug delivery system, it is essential to design polymeric carriers with tissue-specific targeting capacity. Previously, we showed that polyvinylpyrrolidone (PVP) was the most suitable polymeric carrier for prolonging the blood-residency of drugs, and was one of the best parent polymers to design the polymeric carriers with targeting capacity. In this study, we synthesized some hydrophobic PVP derivatives, poly(vinylpyrrolidone-co-styrene) [poly(VP-co-S)] and poly(vinylpyrrolidone-co-vinyl laurate) [poly(VP-co-VL)], and assessed their biopharmaceutical properties after intravenous administration in mice. The elimination of hydrophobic PVP derivatives from blood was the same as PVP, and the plasma half-lives of poly(VP-co-S) were almost similar to that of poly(VP-co-VL). Poly(VP-co-VL) efficiently accumulated in the spleen, whereas poly(VP-co-S) effectively accumulated in the liver. The level of poly(VP-co-VL) in the spleen was about 20 times higher than PVP and poly(VP-co-S). These hydrophobic PVP derivatives did not show any cytotoxicity against endothelial cells in vitro. Thus, poly(VP-co-VL) may be a useful polymeric carrier for drug delivery to the spleen. This study will provide useful information to design optimal polymeric carriers with targeting capacity to the spleen and liver.

Animals↗
PubMed2004

Design of a pH-sensitive polymeric carrier for drug release and its application in cancer therapy.

PURPOSE: In this study, to optimize the polymeric drug delivery system for cancer chemotherapy, we developed a new pH-sensitive polymeric carrier, poly(vinylpyrrolidone-co-dimethylmaleic anhydride) [PVD], that could gradually release native form of drugs with full activity, from the conjugates in response to changes in pH. We examined the usefulness of PVD as a polymeric drug carrier. EXPERIMENTAL DESIGN: PVD was radically synthesized with vinylpyrrolidone and 2,3-dimethylmaleic anhydride, which is known to be a pH-reversible amino-protecting reagent. Conjugates between PVD and other drugs, such as Adriamycin (ADR), were prepared under the slightly basic conditions (pH 8.5). The drug-release pattern and the antitumor activity of PVD were examined. RESULTS: At pH 8.5, the release of the drugs from the conjugate was not observed. In contrast, PVD could release fully active drugs in the native form in response to the change in pH near neutrality, and gradually released drugs at neutral pH (7.0) and slightly acidic pH (6.0). The drug-release pattern in serum was almost similar to that observed during these physiological conditions. The PVD-conjugated ADR showed superior antitumor activity against sarcoma-180 solid tumor in mice, and it had less toxic side effects than free ADR. This enhancement in the antitumor therapeutic window may be due to not only the improvement of plasma half-lives and tumor accumulation of ADR, but also its controlled and sustained release from the conjugates in vivo. CONCLUSIONS: These results indicate that PVD is an effective polymeric carrier for optimizing cancer therapy.

Animals↗