Ring-opening metathesis polymerization-based synthesis of ICG-containing amphiphilic triblock copolymers for in vivo tumor imaging.

Water-soluble triblock copolymers consisting of hydrophobic-hydrophilic-dye segments were synthesized by ring-opening metathesis polymerization (ROMP) of norbornadiene monomers, copper-catalyzed click reaction, osmium-catalyzed dihydroxylation, and the following transformations. These polymers in aqueous conditions could form spherical assemblies, whose diameters were 50-60 nm by TEM measurement. From in vivo optical imaging experiments, the spherical assemblies of these copolymers could be efficiently accumulated in tumor cells.

A randomized phase II study of cisplatin/5-FU concurrent chemoradiotherapy for esophageal cancer: Short-term infusion versus protracted infusion chemotherapy (KROSG0101/JROSG021).

Purpose: A randomized phase II study was conducted to compare the toxicity and efficacy of combining short-term chemotherapy (CT) or protracted CT with radiotherapy (RT) for esophageal cancer.

Materials And Methods: Eligible patients were <75 years and with performance status (PS) of 0-2, and had stages II-IVA esophageal cancer. Two cycles of cisplatin 70 mg/m(2) for 1 day and 5FU 700 mg/m(2) for 5 days (arm A) or cisplatin 7 mg/m(2) for 10 days and 5FU 250 mg/m(2) for 14 days (arm B) were given with RT of 60Gy/30 fractions/7 weeks (1-week split).

The Akt/mTOR pathway assures the synthesis of HIF-1alpha protein in a glucose- and reoxygenation-dependent manner in irradiated tumors.

Transcriptional activity of HIF-1 (hypoxia-inducible factor-1) has been reported to be up-regulated in solid tumors after ionizing radiation; however, the molecular mechanism underlying the response remains to be elucidated. In the present study, we performed a series of molecular imaging experiments using a HIF-1-dependent reporter gene, 5HREp-ODD-luc, and found an essential role of the Akt/mTOR pathway. Hypoxic tumor cells distant from blood vessels were dramatically reoxygenated at 24 h postirradiation, and HIF-1 activity increased as HIF-1alpha accumulated in the reoxygenated regions.

IL12RB2 and ABCA1 genes are associated with susceptibility to radiation dermatitis.

Purpose: Severe acute radiation dermatitis is observed in approximately 5% to 10% of patients who receive whole-breast radiotherapy. Several factors, including treatment-related and patient-oriented factors, are involved in susceptibility to severe dermatitis. Genetic factors are also thought to be related to a patient's susceptibility to severe dermatitis.

Geometrical differences in target volumes between slow CT and 4D CT imaging in stereotactic body radiotherapy for lung tumors in the upper and middle lobe.

Since stereotactic body radiotherapy (SBRT) was started for patients with lung tumor in 1998 in our institution, x-ray fluoroscopic examination and slow computed tomography (CT) scan with a rotation time of 4 s have been routinely applied to determine target volumes. When lung tumor motion observed with x-ray fluoroscopy is larger than 8 mm, diaphragm control (DC) is used to reduce tumor motion during respiration. After the installation of a four-dimensional (4D) CT scanner in 2006, 4D CT images have been supplementarily acquired to determine target volumes.

TS-1 enhances the effect of radiotherapy by suppressing radiation-induced hypoxia-inducible factor-1 activation and inducing endothelial cell apoptosis.

The therapeutic effect of concurrent chemoradiotherapy with TS-1 has been confirmed in various solid tumors; however, the detailed mechanism of action has not yet been fully elucidated. In the present study, we identified hypoxia-inducible factor-1 (HIF-1) as one of the targets of TS-1 in chemoradiotherapy. In growth delay assays using a tumor xenograft of non-small-cell lung carcinoma, H441, TS-1 treatment enhanced the therapeutic effect of single gamma-ray radiotherapy (14 Gy) and significantly delayed tumor growth by 1.

Diameter of tumor blood vessels is a good parameter to estimate HIF-1-active regions in solid tumors.

As the transcriptional activity of hypoxia-inducible factor 1 (HIF-1) is associated with resistance of tumor cells to current antitumor therapies, the spatiotemporal dynamics of HIF-1-active regions has been of great interest as a therapeutic target. In the present study, we established a unique cancer cell line, which changes color HIF-1-dependently, and monitored it during tumor progression. In imaging experiments, HIF-1-active cells appeared over the tumor xenograft, but dramatically decreased in number as blood vessels developed around the tumor.

Development of a three-dimensionally movable phantom system for dosimetric verifications.

The authors developed a three-dimensionally movable phantom system (3D movable phantom system) which can reproduce three-dimensional movements to experimentally verify the impact of radiotherapy treatment-related movements on dose distribution. The phantom system consists of three integrated components: a three-dimensional driving mechanism (3D driving mechanism), computer control system, and phantoms for film dosimetry. The 3D driving mechanism is a quintessential part of this system.

Accelerated fractionation versus conventional fractionation radiation therapy for glottic cancer of T1-2N0M0 Phase III study: Japan Clinical Oncology Group study (JCOG 0701).

A randomized Phase III study was started in Japan to demonstrate the non-inferiority of survival of accelerated fractionation radiation therapy (2.4 Gy/fr) with conventional fractionation radiation therapy (2 Gy/fr) in patients with T1-2N0M0 glottic cancer. This study began in September 2007, and a total of 360 patients will be accrued from 22 institutions within 4 years.

Stereotactic body radiotherapy for oligometastatic lung tumors.

Purpose: Since 1998, we have treated primary and oligometastatic lung tumors with stereotactic body radiotherapy (SBRT). The term "oligometastasis" is used to indicate a small number of metastases limited to an organ. We evaluated our clinical experience of SBRT for oligometastatic lung tumors.

Comparisons of the impact of systematic uncertainties in patient setup and prostate motion on doses to the target among different plans for definitive external-beam radiotherapy for prostate cancer.

Background: We aimed to compare the impact of systematic uncertainties in patient setup and prostate motion on three different external-beam radiotherapy protocols for prostate cancer.

Methods: To simulate possible near-maximum systematic errors, the isocenter position was shifted to eight points with +/-1.65 SD of the integrated uncertainty value along each axis that was expected to include 5%-95% of the total systematic uncertainties in each direction.

Taip2 is a novel cell death-related gene expressed in the brain during development.

TAIP2 was isolated as one of the homologous genes of TAIP3 (TGF-beta-up-regulated apoptosis-inducing-protein chromosome 3). The transcript of the mouse counterpart of TAIP2, designated mTaip2, was detected in several tissue specimens from embryos to adults, while mTaip2 was dominantly expressed in the embryonic brain. The overexpression of the full-length mTaip2 induced cell death in various cell lines.

Emission under hypoxia: one-electron reduction and fluorescence characteristics of an indolequinone-coumarin conjugate.

A characteristic feature of the reactivity of indolequinone derivatives, substituents of which can be removed by one-electron reduction under hypoxic conditions, was applied to the development of a new class of fluorescent probes for disease-relevant hypoxia. A reducing indolequinone parent molecule conjugated with fluorescent coumarin chromophores could suppress efficiently the fluorescence emission of the coumarin moieties by an intramolecular electron-transfer quenching mechanism and a conventional internal-filter effect. Under hypoxic conditions, however, the conjugate, denoted IQ-Cou, underwent a one-electron reduction triggered by X irradiation or the action of a reduction enzyme to release a fluorescent coumarin chromophore, whereupon an intense fluorescence emission with a maximum intensity at 420 nm was observed.

Feasibility of accelerated partial breast irradiation using three-dimensional conformal radiation therapy for Japanese women: a theoretical plan using six patients' CT data.

Background: Several methods have been reported for accelerated partial breast irradiation (APBI), but in Japan, there are few facilities where brachytherapy or intra-operative radiotherapy is available. Japanese women have smaller physiques than American women in general. Thus, we developed external beam plans for APBI using computed tomography (CT) data of Japanese patients, to investigate whether APBI using three-dimensional conformal radiation therapy is safely applicable for Japanese women, while verifying the dose distributions.

Current status of accelerated partial breast irradiation.

Accelerated partial breast irradiation (APBI) is a radiotherapy method used in breast-conserving therapy. In APBI, the tumor bed is topically irradiated over a short period after breast-conserving surgery. The fundamental concept underlying APBI is that more than 70% of ipsilateral breast tumor recurrence occurs in the neighborhood of the original tumor, and that hypofractionated radiotherapy can be applied safely when the irradiated volume is small enough.

Near-infrared fluorescent labeled peptosome for application to cancer imaging.

Nonionic amphiphilic copolypeptides, which were composed of hydrophilic poly(sarcosine) and hydrophobic poly(gamma-methyl L-glutamate) blocks, were synthesized with varying chain lengths of the blocks. The polypeptides having a suitable hydrophilic and hydrophobic balance were found to form vesicular assemblies of 100 nm size in buffer, which was evidenced by the TEM observation, the DLS analysis, and the encapsulation experiment. The genuine peptide vesicles, peptosomes, were labeled with a near-infrared fluorescence (NIRF) probe.

Evaluation of mass-like consolidation after stereotactic body radiation therapy for lung tumors.

Background: The purpose of this study was to evaluate the characteristics of mass-like consolidation of the lung on computed tomography (CT) after stereotactic body radiation therapy (SBRT) retrospectively.

Methods: Forty lung tumors in 37 patients who underwent SBRT were evaluated. Mass-like consolidation was defined as a dense consolidation that newly appeared over or around the original tumor, which included radiation-induced lung injury (RILI) and local recurrence.

In vitro heat generation by ferrimagnetic maghemite microspheres for hyperthermic treatment of cancer under an alternating magnetic field.

Ferrimagnetic materials can be expected to be useful as thermo seeds for hyperthermic treatment of cancer, especially where the cancer is located in deep parts of body, as they can generate heat by magnetic hysteretic loss when they are placed in an alternating magnetic field. Recently, it was reported that ferrimagnetic maghemite (gamma-Fe2O3) microspheres 20-30 microm in diameter prepared in aqueous solution can show excellent heat generating ability. However, these microspheres have many cracks on their surfaces.

Patterns of care study of breast-conserving therapy in Japan: comparison of the treatment process between 1995 1997 and 1999 2001 surveys.

Background: The Japan Patterns of Care Study (JPCS) conducted two national surveys to identify changes associated with the treatment process of care for patients undergoing breast-conserving therapy (BCT). Between the two national surveys, the Japanese Breast Cancer Society published its treatment guideline for BCT.

Method: The first survey collected data on 865 patients treated between 1995 and 1997 (JPCS-1), and the second on 746 patients treated between1999 and 2001 (JPCS-2) by extramural audits.

Development of a new concept automatic frequency controller for an ultrasmall C-band linear accelerator guide.

We are developing a four-dimensional, image-guided radiotherapy system with a gimbaled x-ray head. The system has pursuing irradiation capability in addition to precise irradiation capability, owing to its agile x-ray head. The moving x-ray head requires a very small C-band accelerator guide.

Hypofractionated stereotactic radiotherapy (HypoFXSRT) for stage I non-small cell lung cancer: updated results of 257 patients in a Japanese multi-institutional study.

Introduction: Hypofractionated stereotactic radiotherapy (HypoFXSRT) has recently been used for the treatment of small lung tumors. We retrospectively analyzed the treatment outcome of HypoFXSRT for stage I non-small cell lung cancer (NSCLC) treated in a Japanese multi-institutional study.

Methods: This is a retrospective study to review 257 patients with stage I NSCLC (median age, 74 years: 164 T1N0M0, 93 T2N0M0) were treated with HypoFXSRT alone at 14 institutions.

A Japan clinical oncology group trial for stereotactic body radiation therapy of non-small cell lung cancer.

Stereotactic body radiation therapy (SBRT) is a new treatment modality. To confirm the safety and efficacy, the Radiation Therapy Study Group of the Japan Clinical Oncology Group (JCOG) has started a phase II study of SBRT for stage IA non-small cell lung cancer (JCOG 0403). This study is ongoing with a strict quality control and quality assurance program, and the results will indicate whether a future phase III trial comparing SBRT with surgery is warranted.

The combination of hypoxia-response enhancers and an oxygen-dependent proteolytic motif enables real-time imaging of absolute HIF-1 activity in tumor xenografts.

The transcriptional activity of hypoxia-inducible factor-1 (HIF-1) is associated with tumor malignancies; therefore, it is important to comprehend its dynamism in solid tumors. However, a molecular imaging strategy to accurately access it remains to be developed. We constructed here a novel HIF-1-dependent reporter gene, 5HREp-ODD-luc, in which 5 copies of the hypoxia-response element (5HRE) enhance expression of the oxygen-dependent degradation (ODD) domain and luciferase (luc) fusion under hypoxia.

Hypoxia inducible factor-1 influences sensitivity to paclitaxel of human lung cancer cell lines under normoxic conditions.

Paclitaxel (PTX) is an anticancer drug that is effective against a wide range of solid tumors. The effect of PTX on two human lung cancer cell lines, PC14PE6 and NCI-H441 cells, was examined in an orthotopically transplanted animal model with an in vivo imaging devise. Although PTX effectively suppressed tumor growth and improved survival rate in NCI-H441, it did not influence these in PC14PE6.