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Hiromitsu Jinno

Publications and source records attributed to Hiromitsu Jinno.

At least 19 recordsLinked to original sources
PubMed2007

Development of gene vectors for pinpoint targeting to human hepatocytes by cationically modified polymer complexes.

We developed a vector that might enable gene therapy of metabolic liver disease or hepatoma. Here we demonstrate the use of cationically modified biocompatible phospholipid polymer conjugated with hepatitis B surface (HBs) antigen for the specific transfer of genes into human hepatocytes. Poly(2-methacryloyloxyethyl phosphorylcholine (MPC)- co-N,N-dimethylaminoethyl methacrylate (DMAEMA)-co- p-nitrophenylcarbonyloxyethyl methacrylate(NPMA))(polyMDN) was prepared as a frame of vector. The specific expression of sFlt-1 or GFP by polyMDN conjugated with HBs containing plasmid (plasmid/polyMDN-HBs), polyMDN containing plasmid (plasmid/polyMDN), plasmid only and PBS were assessed in tumor cells (HepG2 or WiDr) in vitro and in vivo. The histological findings, organ weight changes, and degree of liver dysfunction were examined in the mice administered by several reagents. The sFlt-1 and GFP expression was observed only in the HepG2 cells transfected with sFlt-1 or GFP/polyMDN-HBs. None of the side effects mentioned above was observed. In conclusion, these results suggest that polyMDN-HBs is a human hepatocyte-specific gene delivery vector that might not have serious side effects.

Adenocarcinoma↗
PubMed2006

Anti-tumor effect in an in vivo model by human-derived pancreatic RNase with basic fibroblast growth factor insertional fusion protein through antiangiogenic properties.

It is thought that the export of angiogenic fibroblast growth factors (FGF) from tumors may be involved in the onset of tumor angiogenesis. To create a new active targeting drug that inhibits the tumor angiogenic process without toxicities to normal cells, human basic FGF (h-bFGF) was inserted genetically into the Gly89 position of cross-linked RNase1 (the ribonuclease inhibitor protein [RI] binding site of cross-linked human pancreatic RNase) to prevent stereospecific binding to RI. The resultant insertional-fusion protein (CL-RFN89) was active both as h-bFGF and as RNase1. Furthermore, it acquired an additional ability of evading RI through steric blockade of RI binding caused by the fused h-bFGF domain. In the present study, the effect of the resultant protein, CL-RFN89, on the antitumor response though its antiangiogenic properties was investigated in an in vivo model. Continuous systemic treatment with CL-RFN89 significantly inhibited the growth of human A431 squamous cell carcinomas in vivo. Seven days of treatment with CL-RFN89 resulted in a 58.2% inhibition of tumor growth compared with control mice (P < 0.0001). Furthermore, immunohistochemistry using a rat antimouse CD31 antibody showed that treatment with CL-RFN89 reduced tumor vascularization. These findings identify CL-RFN89 as a potent systemic inhibitor of tumor growth as a result of its antiangiogenic properties. This protein appears to be a new systemic antitumor agent.

Angiogenesis Inhibitors↗
PubMed2006

[The evolving role of endocrine therapy for breast cancer].

The indirect comparison of LHRH agonist with tamoxifen showed similar efficacy in the adjuvant treatment of premenopausal endocrine-responsive breast cancer patients. Furthermore, LHRH agonist is as effective as cyclophosphamide, methotrexate and 5-fluorouracil chemotherapy. Data concerning combination of LHRH agonist with third-generation aromatase inhibitors are still lacking. Moreover, duration of therapy with LHRH agonist is still a matter of debate. In randomized clinical trials, each of the third-generation aromatase inhibitors (AIs) has demonstrated efficacy in the adjuvant treatment of postmenopausal women with receptor' -positive tumors. Anastrozole has been shown to improve disease-free survival when compared with tamoxifen, letrozole has been shown to further reduce the rate of breast cancer events when given as extended adjuvant therapy in women completing between 4.5 and 6 years of tamoxifen, and exemestane has been shown to improve disease-free survival when substituted for tamoxifen after an initial 2-3 years of adjuvant therapy. Although long-term follow-up for safety and overall survival continues in each of these trials, currently available data suggest that an AI should now be included as part of adjuvant endocrine therapy for the great majority of receptor-positive postmenopausal patients.

Aromatase Inhibitors↗
PubMed2005

Increasing age does not affect efficacy of sentinel lymph node biopsy using smaller-sized technetium-99m tin colloids for breast cancer patients.

BACKGROUND: Increasing age of breast cancer patients was reported to cause not only failure of sentinel lymph node (SLN) identification but also false negative results. METHODS: A retrospective review was conducted of breast cancer patients who underwent sentinel lymph node biopsy (SLNB) using small-sized technetium-99m-labeled tin colloid (particle size: 200-400 nm in diameter). A comparison between 82 patients who were less than 60 years and 40 patients who were > or =60 years of age was performed to evaluate the efficacy of SLNB using the small-sized tin colloid in older patients. RESULTS: One hundred twenty-two clinically node-negative breast cancer patients underwent SLNB. Apart from age, there were no statistically significant differences between the younger patients and the older patients in terms of the clinicopathologic characteristics. Successful mapping rates, false negative rates, and accuracy were comparable between the 2 groups. CONCLUSIONS: SLNB using the small-sized tin colloid was not affected by increasing age.

Adult↗
PubMed2004

Evaluation of novel modified tangential irradiation technique for breast cancer patients using dose-volume histograms.

PURPOSE: We have previously reported that entire axillary lymph node regions could be irradiated by the modified tangential irradiation technique (MTIT). In this study, MTIT was compared with a conventional irradiation technique (CTIT) using dose-volume histograms to verify how adequately MTIT covers the breast and axillary lymph node region and the extent to which it involves the lung and heart. METHODS AND MATERIALS: Forty-four patients with early-stage breast cancer were treated by lumpectomy, axillary dissection, and postoperative radiotherapy. Twenty-two patients were treated with MTIT and 22 with CTIT. In 25 patients, the breast tumor was on the left and in 19 on the right. During axillary dissection, surgical clips were left as markers at the border of the axillary lymph node region. MTIT was planned by setting the dorsal edge of the radiation field on a lateral-view simulator film at the dorsal edge of the humeral head and the cranial edge of the radiation field at the caudal edge of the humeral head. CTIT was planned to ensure radiation of the breast tissue without considering the axillary region. In this study, all patients underwent computed tomography, and the CT data were transmitted on-line to a radiotherapy planning system, in which the dose-distribution computed tomography images and dose-volume histograms were calculated by defining the breast, axillary region (levels I, II, and III), lung, and heart region. RESULTS: Dose-volume histogram analysis demonstrated that breast tissue was radiated with an 86.5-100% volume (median 96.5%) by MTIT and an 83-100% volume (median, 95%) by CTIT at >95% of the isocenter dose. The axillary lymph node regions at Levels I, II, and III were irradiated with 84-100% (median, 94.5%), 59-100% (median, 89%), and 70-100% (median, 89.5%) volumes, respectively, by MTIT and with 2-84% (median, 38%), 0-53% (median, 15%), and 0-31% (median, 0%) volumes, respectively, by CTIT at >70% of the isocenter dose. The ipsilateral lung was irradiated with a 5-22% volume (median, 11.5%) by MTIT and 5-15% volume (median 9%) by CTIT at >90% of the isocenter dose. In all 25 left-sided breast cancer patients, the volumes irradiated with an 80% isocenter dose were <30 cm(3). CONCLUSION: The results of our study demonstrated that the breast tissue was sufficiently irradiated with both CTIT and MTIT planning, the axillary lymph node areas irradiated by MTIT were much wider than those irradiated by CTIT at all levels, and the lung and heart volumes irradiated by MTIT were small.

Adult↗
PubMed2004

The evolution of primary chemotherapy in breast cancer treatment.

Primary chemotherapy may be thought of as having evolved over three generations. First-generation primary chemotherapy followed trials which proved that the prognosis of breast cancer patients receiving primary chemotherapy was the same as that of patients receiving post-operative chemotherapy. Second-generation primary chemotherapy followed trials which demonstrated that regimens containing anthracyclines and taxanes yielded complete pathological response rates (pCR)of over 20%. Third-generation primary chemotherapy followed trials which demonstrated that inclusion of newer agents, such as trastuzumab and capetitabine, in combination with taxanes could yield pathological CR rates of over 30%. In third-generation primary chemotherapy, predictive factors, especially those analyzed by DNA array analysis, play a key role. Other issues, including the relevance of sentinel node biopsy after primary chemotherapy and the importance of marking the site of the primary tumor before primary chemotherapy in cases showing cCR, are highlighted. This article deals with the history of the evolution of primary chemotherapy, along with a discussion of some relevant issues.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Lymphoscintigraphy for the visualization of sentinel lymph nodes and body contour.

BACKGROUND: It is important to create clear lymphoscintigraphic images when assessing the sentinel lymph nodes. This clarity needs to reach a level where the sentinel lymph nodes (SLNs) and the body contour are clearly visible. We have developed a simple image processing method using the division of primary and scattered photon counts. METHODS: Twenty patients with breast cancer were enrolled in this study. Manual injection of 150 MBq of Tc-99m tin colloid with small particle size into the peritumoral and subdermal regions was performed. Lymphoscintigraphy using a conventional gamma camera was performed three hours after the injection. Dual energy windows were set from 130 to 150 keV for the primary photons and 70 to 110 keV for the scattered photons. An anterior view of the chest and a lateral view from the affected side were obtained. Primary photon image counts were divided by the scattered photon image counts for each pixel after the addition of some constant counts to each pixel of the acquired image to improve the contrast of the scintigrams. We evaluated the ability to accurately visualize the body contour and the SLNs on the processed image. RESULTS: Image processing time was 20 to 40 seconds for each patient. In every case, the processed image clearly identified the body contour. The processed images allowed the identification of the same number of SLNs as the original images. CONCLUSIONS: This proposed method for image processing is a simple and useful means to clearly visualize both SLNs and body contours.

Adult↗
PubMed2004

Recent development of sentinel lymph node biopsy for breast cancer in Japan.

The number of breast cancer cases undergoing sentinel lymph node biopsy (SLNB) has been increasing with the number of articles published in Japan. SLNB using the dye method alone is performed in about one-third of patients. Analysis of questionnaire responses from 40 institutions in Japan revealed an identification rate by the dye method alone of 87%, compared with 96% using the combined method; the combined method is now recognized in Japan as superior to the dye method alone. No dyes have been specifically approved by the government for use in SLNB, and physicians have been using several inappropriate dyes as tracers for SLNB, such as indocyanine green, patent blue, indigo carmine, and isosulfan blue. The colloidal radiotracers used in Japan include tin colloid, stannous phytate, rhenium sulfate and human serum albumin. Albumin colloid and sulfur colloid are not commercially available in Japan. Small-size tin colloids, stannous phytate and rhenium sulfate all yield good results in terms of detection and false-negative rates. Provided that the surgeon has adequate experience in SLNB, a negative sentinel node can serve as a substitute for negative results from axillary lymph node dissection. Although many institutions have introduced SLNB, few reports have focused on the results of SLNB without axillary dissection because of short follow-up times and small number of patients. The final decision as to whether SLNB is an adequate substitute for axillary dissection awaits the results of prospective randomized trials.

Axilla↗
PubMed2004

[Adjuvant chemotherapy for breast cancer--a current controversy].

EBCTCG meta-analysis revealed a significant reduction in mortality in patients receiving chemotherapy irrespective of nodal status and ER status. Compared with CMF, 5-year RFS and OS favored the anthracycline-containing regimens, 57% vs 54% (p = 0.006) and 72% vs 69% (p = 0.02), respectively. No survival benefit was obtained for CMF durations greater than 6 months. Delaying radiation therapy for several months after breast-conserving surgery until the completion of adjuvant chemotherapy appears safe and may be preferable for patients at high risk of distant metastasis. No difference in disease-free survival for the 3 dose levels of doxorubicin (60, 75, and 90 mg/m2) was found. Higher doses (100 mg/m2) of epirubicin led to a high survival rate in women with poor-prognosis disease. Dose-dense therapy seems promising but still needs further investigation. Incorporation of taxanes into adjuvant chemotherapy for early breast cancer is also controversial.

Anthracyclines↗
PubMed2004

[Current status of sentinel node adenectomy and future perspectives].

Sentinel node adenectomy has rapidly been accepted in recent years. A survey performed under the auspices of the Japanese Breast Cancer Society revealed that about 40% of institutions in Japan have already introduced sentinel lymph adenectomy. Analysis of questionnaire responses from 40 institutions in Japan revealed an identification rate using the dye method alone of 87% compared with 96% using the combined method. The identification rate and the false-negative rate are about the same among various methods used such as colloidal radiotracers, injection site, use of lymphoscintigraphy, etc., provided that the surgeon has adequate experience. It is recommended that the surgeon should start to perform sentinel node adenectomy after experiencing more than 60 cases, because there is a learning curve. Some investigators are devising other methods to replace the RI method, for example, using magnetic particles instead of RI colloid and detecting them using magnetic probes. and a trial to detect lymphatic flow with CT after local injection of contrast medium is also being conducted. Sentinel node adenectomy may become a standard technique for early breast cancer patients in the near future.

Breast Neoplasms↗
PubMed2003

Port site metastasis of sigmoid colon cancer after a laparoscopic sigmoidectomy: report of a case.

A 75-year-old woman with TNM stage I (T2, N0, M0) sigmoid colon adenocarcinoma underwent a laparoscopy-assisted sigmoidectomy. Five months later, the patient developed two subcutaneous metastases at two trocar sites. A second operation was performed and two abdominal wall masses were resected, but the operation revealed no evidence of peritoneal dissemination, liver metastasis, or lymph node metastasis. The histological findings confirmed the diagnosis of metastatic carcinoma of the sigmoid colon. Large-scale studies have shown the actual rate of port site metastasis to be similar to that observed in open surgery, and therefore the rate is much lower than that initially reported in small studies. However, the metastatic mechanism has not yet been clarified. These results suggest that port site metastasis can be prevented as effectively as during open surgery by utilizing accurate operating skills based on the sound principles of tumor surgery. Therefore, it is very important that appropriate operating procedures and an effective training system are established.

Adenocarcinoma↗
PubMed2002

The role of neoadjuvant chemotherapy for breast cancer treatment.

Neoadjuvant chemotherapy has become popular, especially for patients with advanced breast cancer. The pros and cons of neoadjuvant chemotherapy for treating breast cancer patients are reviewed. The advantages of neoadjuvant chemotherapy are 1) overall survival and recurrence-free survival rate are the same as post-operative chemotherapy, 2) serves as an in vivo sensitivity test, 3) increases the rate of breast conserving therapy, 4) facilitates the study of cancer biology. On the other hand, the disadvantages of neoadjuvant chemotherapy are 1) it modifies the stage, 2) treatment delay of PD cases, 3) residual intraductal component may be left behind after breast conserving surgery, 4) there are some cases of over-treatment. Combination chemotherapy is one possible way to increase the pathological CR rate, although the optimal order and cycles have not been determined. To avoid residual cancer cells after breast conserving surgery, the shrinkage pattern should be evaluated by MRI. Core needle biopsy should be performed before neoadjuvant chemotherapy to avoid over-treatment. It is essential to develop more effective regimens and stratify patients based on predictive factors.

Antineoplastic Agents↗
PubMed2002

Sentinel lymph node biopsy in breast cancer using technetium-99m tin colloids of different sizes.

Axillary lymph node dissection (ALND) in the treatment of breast cancer is essential for predicting the prognosis and regional control of the tumor. At the same time ALND is associated with pain, numbness and sometimes lymphedema. Sentinel lymph node biopsy (SLNB) is a potential alternative procedure to conventional ALND in clinically node-negative breast cancer. In this study, we prepared the technetium-99m-labeled tin colloids with different sizes and compared their efficacy in SLNB. From September 1998 to February 2002, 184 clinically node-negative breast cancer patients were enrolled in the study at Keio University Hospital. Sentinel lymph nodes (SLNs) were identified by both blue dye and radioisotope. We prepared small-sized technetium-99m-labeled tin colloid (particle size: 200-400 nm in diameter). Regular-sized technetium-99m-labeled tin colloid is 400-1000 nm in diameter. In 74 patients, a SLNB was performed using regular-sized tin colloid; small-sized tin colloid was used in 110 patients. Subsequently, all of the patients were immediately followed by ALND. All dissected lymph nodes were evaluated by routine histopathological examination. The clinicopathological characteristics of the two groups were comparable. The lymphoscintigram detected SLN more frequently in the small-sized colloid group than in the regular-sized colloid group (P < 0.01). Small-sized tin colloid was also superior to regular-sized tin colloid in the SLN identification rate (97.3% versus 86.5%; P = 0.01). The mean value for ex vivo counts of the hottest sentinel lymph nodes of the small-sized colloid group was significantly higher than the counts of the regular-sized colloid group (P < 0.01). There was no significant difference in the accuracy between the two groups. It was concluded that SLNB using the small-sized tin colloid was technically feasible and provided higher detection and identification rates than the regular-sized tin colloid.

Adult↗
PubMed2002

Overview: current status of breast conserving therapy in Japan.

Breast conserving operations have become the standard operation for early breast cancer. They were performed in about 40% of all breast cancer patients in Japan in 2000, and the percentage is still increasing. Ductal carcinoma in situ (DCIS) accounts for about 7% of all breast cancers and breast conserving operations for DCIS have been followed by a low in-breast recurrence rate, leading to wider indications for breast conserving operations as screening mammography has come to be used in Japan. In-breast recurrence is correlated to surgical margin status. It is important to evaluate the surgical margin for volume of cancer cell nests as well as for positivity. Neoadjuvant chemotherapy has become popular as an in vivo sensitivity test and as a means of down-staging to increase the possibility of performing a breast conserving operation. There are two patterns of shrinkage when neoadjuvant chemotherapy is effective: cocentric and honeycomb, and the pattern of residual cancer cell nests must be determined before surgery. MRI is an effective method of evaluating residual cancer cell nests. The in-breast recurrence rate after down-staging to perform breast conserving operations is reported to be higher than among candidates for breast conserving operation at the start. Sentinel node biopsy techniques and endoscopic operations are now being assessed in conjunction with breast conserving operations. The current status of breast conserving operations in Japan is reviewed in comparison with their status in Western countries.

Breast Neoplasms↗
PubMed2002

Preventive efficacy of receptor class selective retinoids on HER-2/neu oncogene expressing preneoplastic human mammary epithelial cells.

Aberrant proliferation is an early-occurring event in vitro prior to tumorigenesis in vivo in the multistep process of carcinogenesis. Inhibition of aberrant proliferation therefore may represent a useful biomarker to evaluate the efficacy of chemopreventive agents. Retinoids have exhibited preventive efficacy in vitro and in vivo predominantly through the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). Clinically relevant biochemical and cellular mechanistic endpoints for chemopreventive effects of retinoids should provide novel biomarkers. The present study was designed to examine the preventive efficacy of natural retinoids, all-trans-retinoic acid (ATRA) and 9-cis-retinoic acid (9cisRA), and to identify the possible mechanisms for their effects using the HER-2/neu oncogene expressing preneoplastic human mammary epithelial 184-B5/HER cells. Seven-day treatment with ATRA and 9cisRA exhibited a dose-dependent growth inhibition. Long-term (21 days) treatment with IC20 doses of 50 nM ATRA and 100 nM 9cisRA inhibited anchorage-dependent colony forming efficiency by about 75.4% (p<0.01) and 84.9% (p<0.01), respectively. Cell cycle analysis revealed that a 24-h treatment with IC90 doses of 2 microM ATRA and 3 microM 9cisRA accumulates cells in the G0/G1 phase and inhibit S and/or G2/M phase of the cell cycle. ATRA and 9cisRA induced an 11-fold (p=0.03) and a 9-fold (p=0.04) increase in subG0/G1 (apoptotic) population relative to the solvent control, respectively. ATRA and 9cisRA induced 77% (p=0.01) and 51% (p=0.02) decrease in tyrosine kinase immunoreactivity, respectively. Similarly, the two retinoids caused almost a 50% (p=0.01) down-regulation of Bcl-2 immunoreactivity. Western blot analysis revealed that ATRA induced an increase in RARbeta expression and a decrease in RARgamma expression, while 9cisRA down-regulated RXRalpha expression. These data demonstrate that ATRA and 9cisRA may inhibit HER-2/neu induced aberrant proliferation in part by retarding cell cycle progression, down-regulating HER-2/neu-mediated signal transduction and inducing Bcl-2-dependent apoptosis through a retinoid receptor-mediated mechanism.

Alitretinoin↗
PubMed2002

[Developments in endocrine therapy for breast cancer].

After the usefulness of ovariectomy in breast cancer patients was demonstrated, endocrine therapy has been one of the most effective treatments of breast cancer. Thereafter, it became clear that estrogen receptors (ERs) existed in the cells of breast cancer. After it was found that ERs could be used as a predictive factor of endocrine therapy for breast cancer, the validity of endocrine therapy has became more certain. Tamoxifen, a major selective estrogen receptor modulator, is the first agent which has shown evidence of improving survival time and disease-free survival time in the treatment of breast cancer, and is the standard treatment, widely used in the treatment of breast cancer all over the world. LH-RH analogue, commonly used in ablation treatment among premenopausal women, produces the same effect as ovariectomy, and recently has shown good results equivalent to chemotherapy in premenopausal breast cancer treatment. Furthermore, aromatase inhibitors as a form of ablation treatment of postmenopausal women have been used recently. In comparison with tamoxifen, aromatase inhibitors have revealed the same or more effective result in postmenopausal breast cancer treatment. In the near future, endocrine mechanisms in the body and the molecular mechanisms of transcription by ER will be more clearly elucidated, and then new kinds of agent and combined therapies for the endocrine treatment of breast cancer will be developed. Currently, many clinical randomized trials are being conducted to examine the effectiveness of new endocrine treatment. Significant changes are occurring in the endocrine treatment of breast cancer.

Antineoplastic Agents, Hormonal↗
PubMed2002

[Breast cancer].

Adjuvant chemo-endocrine therapy for breast cancer (ACETBC) trial has been the first large scaled clinical trial performed in Japan. Several prospective randomized trials have been performed in Japan since ACETBC-1 trial started in 1985. The effect of oral 5-FU agents had been tested in prospective randomized trials and the statistically marginal effect of oral 5-FU agents in adjuvant settings has been reported. Several trials having CMF as a control arm started in 1996 when CMF combination chemotherapy was approved by the government. The results of these trials have not been published. To perform good clinical trials, it is imperative to construct infrastructures including clinical research coordinator, and abolish governmental regulation of the dose of anticancer agents.

Antineoplastic Combined Chemotherapy Protocols↗