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Biomedical subjects

H Hasegawa

Publications and source records attributed to H Hasegawa.

At least 19 recordsLinked to original sources

Eribulin versus taxane as first-line chemotherapy combined with dual HER2 blockade in patients with HER2-positive locally advanced or metastatic breast cancer: final survival outcomes of the JBCRG-M06/EMERALD study.

BACKGROUND: The phase III JBCRG-M06/EMERALD study was the first to show noninferior progression-free survival (PFS) of eribulin to taxane, combined with dual human epidermal growth factor receptor 2 (HER2) blockade (trastuzumab plus pertuzumab), as a first-line treatment for HER2-positive locally advanced breast cancer or metastatic breast cancer (LABC/MBC). We report final survival outcomes and biomarker analyses of the EMERALD trial. PATIENTS AND METHODS: Patients with HER2-positive LABC/MBC were randomly assigned 1:1 to either eribulin or physician-choice taxane (docetaxel or paclitaxel), both combined with trastuzumab plus pertuzumab, as first-line chemotherapy. PFS and overall survival (OS) were assessed through 30 June 2023 for PFS and 31 December 2024 for OS. Survival outcomes were compared between the eribulin and taxane groups and according to circulating tumor DNA (ctDNA) detection of PIK3CA mutations (PIK3CAm+; E542K, E545K, H1047R, and N345K single nucleotide variants) or HER2 amplification (HER2 amp+; ERBB2 copy number >2.5). RESULTS: Median OS was 78.5 months [95% confidence interval (CI) 64.3-not reached (NR)] for eribulin and was NR for taxane, with a hazard ratio of 1.25 (95% CI 0.92-1.71, log-rank P = 0.19). The 60-month OS rates were 59.7% and 65.2% for eribulin and taxane, respectively. Median OS and 60-month OS rates were numerically lower in ctDNA PIK3CAm+ patients, and greater in ctDNA HER2 amp+ patients for all patients and with stratification by treatment group. There were no statistical interactions between treatment group with either ctDNA PIK3CAm or ctDNA HER2 amp status. Similar patterns were observed for PFS. CONCLUSION: Final survival analysis revealed that median OS exceeded 6 years with eribulin or physician-choice taxane, combined with trastuzumab plus pertuzumab, as first-line chemotherapy for HER2-positive LABC/MBC, with no significant differences between the two groups. ctDNA PIK3CAm+ status was a poor prognostic factor. ctDNA HER2 amp+ was associated with longer survival.

Aged↗

Tissue reaction to poly (lactic-co-glycolic acid) copolymer membrane in rhBMP used rabbit experimental mandibular reconstruction.

A rabbit experimental mandibular defect was reconstructed with 1% atelocollagen gel including rhBMP-2 10microg and a covering a poly (lactic-co-glycolic acid) copolymer (PLGA) membrane. For this experiment, eight male rabbits were used and a histological study was conducted. Our study purpose was to examine the effects and fate of PLGA membrane during bone reconstruction. PLGA membrane was phagocytized by foreign body giant cells and macrophages in the healing course of reconstruction osteogenesis. These histological data suggest that the PLGA membrane was gradually absorbed and replaced by fibrous connective tissue or bone tissue. In the osteogenesis course, the outer periphery of the new bone was maintained by PLGA membrane without expansion.

Animals↗

Three-dimensional observation of reconstruction course of rabbit experimental mandibular defect with rhBMP-2 and atelocollagen gel.

For the experimental animals, eight rabbits were chosen. A bone defect was made and was filled with 1% atelocollagen gel including rhBMP-2 10 microg. The reconstruction course was observed using micro-computed tomography (muCT) in vivo. In muCT observation, the density was slightly elevated at the bone marrow side at day 7, and the phenomenon gradually expanded during the course of this experiment which lasted for 28 days. By utilized muCT, we could construct 3D images, and that process enabled us to visualize bone formation more closely. These data suggest that the experimental animal model muCT and 3D image are extremely useful for follow-up of reconstruction of animal bone defects and that the atelocollagen gel is effective as a carrier of rhBMP-2.

Animals↗

Bone repair of rabbit mandibular transsection using rhBMP-2 and atelocollagen gel.

This experimental was carried out using 12 rabbits. A rabbit experimental mandibular transsection was reconstructed with 10mug of rhBMP-2 and 1% atelocollagen gel. The transsection gap was fixed with a titanium plate and screws, and covered with poly (lactic-co-glycolic acid) co-polymer (PLGA) membrane. Histopathological examination of 1-week specimens revealed that many spindle cells had proliferated and invaded blood clots, and a small amount of immature trabecular bone was formed in the transsection gap. In 2 and 3-week specimens, bone formation was gradually increased in the fibro-vascular tissues of the site. These histological findings were also observed in the control group specimens, but the bone formation was slightly less than in the experimental group. The results suggest the effectiveness of atelocollagen gel as a carrier of rhBMP-2 and PLGA as a covering membrane in this rabbit mandibular transsection reconstruction model.

Animals↗

Influence of cooking method on arsenic retention in cooked rice related to dietary exposure.

Arsenic concentration in raw rice is not only the determinant in actual dietary exposure. Though there have been many reports on arsenic content in raw rice and different tissues of rice plant, little is known about arsenic content retained in cooked rice after being cooked following the traditional cooking methods employed by the people of arsenic epidemic areas. A field level experiment was conducted in Bangladesh to investigate the influence of cooking methods on arsenic retention in cooked rice. Rice samples were collected directly from a severely arsenic affected area and also from an unaffected area, to compare the results. Rice was cooked according to the traditional methods employed by the population of subjected areas. Arsenic concentrations were 0.40+/-0.03 and 0.58+/-0.12 mg/kg in parboiled rice of arsenic affected area, cooked with excess water and 1.35+/-0.04 and 1.59+/-0.07 mg/kg in gruel for BRRI dhan28 and BRRI hybrid dhan1, respectively. In non-parboiled rice, arsenic concentrations were 0.39+/-0.04 and 0.44+/-0.03 mg/kg in rice cooked with excess water and 1.62+/-0.07 and 1.74+/-0.05 mg/kg in gruel for BRRI dhan28 and BRRI hybrid dhan1, respectively. Total arsenic content in rice, cooked with limited water (therefore gruel was absorbed completely by rice) were 0.89+/-0.07 and 1.08+/-0.06 mg/kg (parboiled) and 0.75+/-0.04 and 1.09+/-0.06 mg/kg (non-parboiled) for BRRI dhan28 and BRRI hybrid dhan1, respectively. Water used for cooking rice contained 0.13 and 0.01 mg of As/l for contaminated and non-contaminated areas, respectively. Arsenic concentrations in cooked parboiled and non-parboiled rice and gruel of non-contaminated area were significantly lower (p<0.01) than that of contaminated area. The results imply that cooking of arsenic contaminated rice with arsenic contaminated water increases its concentration in cooked rice.

Arsenic↗

Observation of strong low-lying E1 strength in the two-neutron halo nucleus 11Li.

An exclusive measurement has been made of the Coulomb dissociation of the two-neutron halo nucleus 11Li at 70 MeV/nucleon at RIKEN. Strong low-energy (soft) E1 excitation is observed, peaked at about Ex = 0.6 MeV with B(E1) = 1.42(18) e2fm2 for Erel < or = 3 MeV, which was largely missed in previous measurements. This excitation represents the strongest E1 transition ever observed at such low excitation energies. The spectrum is reproduced well by a three-body model with a strong two-neutron correlation, which is further supported by the E1 non-energy-weighted cluster sum rule.

Journal Article↗

The application of a new stapling device for open surgery (Contour Curved Cutter Stapler) in the laparoscopic resection of rectal cancer.

Anastomotic leakage is a serious problem in the laparoscopic resection of rectal cancer. Although stapling devices and techniques for colorectal or coloanal anastomosis have been improved, laparoscopic anastomosis is still technically difficult and the rate of leakage is high. To resolve this problem, a new stapling device (the Contour Curved Cutter Stapler) for open surgery was applied to the laparoscopic resection of rectal cancer. After intracorporeal mobilization and vessel ligation, a 6-cm Pfannenstiel incision was made to insert the device into the peritoneal cavity, and a hand access device was placed on the site. The head of the device was put through a cutoff of the middle finger of a surgical glove, after which the wrist of the glove was attached to the hand access device. To prevent leakage of CO2 gas through the gap between the shaft and the glove, the shaft covered by the glove was tied, and the gap was filled with bone wax. After re-creation of the pneumoperitoneum, the rectum was transected with the stapling device, and the anastomosis was accomplished by the double stapling technique. This technique enabled a reliable transection of the rectum because of the easy handling of the device and the wide laparoscopic view of the lower rectum in the deep pelvis.

Equipment Design↗

Vanishing N = 20 shell gap: study of excited states in (27,28)Ne.

This Letter reports on the (1)H((28)Ne, (28)Ne) and (1)H((28)Ne, (27)Ne) reactions studied at intermediate energy using a liquid hydrogen target. From the cross section populating the first 2(+) excited state of (28)Ne, and using the previously determined BE(2) value, the neutron quadrupole transition matrix element has been calculated to be M(n)=13.8 +/- 3.7 fm(2). In the neutron knockout reaction, two low-lying excited states were populated in (27)Ne. Only one of them can be interpreted by the sd shell model while the additional state may intrude from the fp shell. These experimental observations are consistent with the presence of fp shell configurations at low excitation energy in (27,28)Ne nuclei caused by a vanishing N=20 shell gap at Z=10.

Journal Article↗

Restoration of thumb abduction damaged by electrical burn using the free dorsalis pedis flap with the extensor hallucis brevis tendon.

The treatment of electrical burn injuries in the hand is difficult and challenging because the burn widely and deeply damages not only the skin and subcutaneous tissue, but also tendon, muscle, ligaments, and bone. Compound defects of the skin and abductor pollicis brevis tendon caused by an electrical injury were reconstructed using a free dorsalis pedis flap including the extensor hallucis brevis tendon. This composite flap is also applicable for reconstruction of thumb abduction, although its usefulness has been reported for reconstruction of defects of the dorsal skin of the hand including the extensor tendons.

Adult↗

Comparative study on DNA sequences of ribosomal DNA and cytochrome c oxidase subunit 1 of mitochondrial DNA among five species of gnathostomes.

The nucleotide sequences of partial 18S, complete internal transcribed spacer region 1 (ITS1), complete 5.8S, complete ITS2 and partial 28S of ribosomal DNA (rDNA) and cytochrome c oxidase subunit 1 of mitochondrial DNA (MCOI) from five species of gnathostomes (G. spinigerum, G. doloresi, G. nipponicum, G. hispidum and G. binucleatum with the former four species being distributed in Japan and Asia) that cause human gnathostomiasis were compared by direct polymerase chain reaction cycle-sequencing. The nucleotide sequences of each region of the18S (613 bp), 5.8S (158 bp) and 28S (598 bp) rDNA from the five species were almost identical. The ITS1 region was different in length for the five species. The nucleotide sequences of each region of ITS2 and partial MCO1 regions were different among the five species. Therefore, these two regions can be used as genetic markers for identification of worms.

Animals↗

[Cavitating pleomorphic carcinoma of the lung; report of a case].

We report a case of a previously healthy 76-year-old male with cavitating pleomorphic carcinoma of the lung. He was admitted because of an abnormal lung shadow on chest X-ray. Computed tomography (CT) showed a well-demarcated nodular shadow within thin-walled cavity in the right upper lobe. Because the lesion was revealed as adenocarcinoma by transbronchial lung biopsy, right upper lobectomy was performed. By histopathologic examination of the resected specimen, the nodule contained a component of spindle cell features and the cavity wall was composed of adenocarcinoma. The final diagnosis was pleomorphic carcinoma. Postoperative course has been uneventful for 12 months after surgery.

Adenocarcinoma↗

Immunohistochemical examination of cytological differentiation in osteosarcomas.

In this immunohistochemical examination, the expression of Runx2, Notch1, Delta and Osteopontin peptides were detected in neoplastic cells in 10 Japanese cases of osteosarcoma. Immunohistochemically, Runx2 peptide expression appeared in the cytoplasm of almost all neoplastic cells of the 10 cases examined. However, Notch1 peptide expression appeared in the cytoplasm of neoplastic cells in the localized and comparatively well-differentiated area of osteosarcoma, which osteoblastic and chondroblastic containing osteoid and/or chondroid tissues. No expression of Notch1 peptide was detected in the fibroblastic and poorly differentiated areas. Delta peptide appearance was nearly the same pattern of Notch1 peptide. Expression of Osteopontin peptide appeared in almost all cells and the strength expression was shown in the area of comparatively well-differentiated tissues. Therefore, these results suggest that Runx2, Notch1, and Delta peptides are closely related to cytological differentiation or acquisition of tissue specific characteristics in neoplastic cells in osteosarcomas.

Adolescent↗

Irrigation-suction straw sheath system for a rigid endoscope during endonasal endoscopic pituitary surgery.

OBJECTIVE: One of the most problematic conditions during endonasal endoscopic pituitary surgery is blurred endoscopic vision caused by blood or bone dust. To address this problem we used a new device, the irrigation-suction straw sheath system originally developed for endoscopic sinus surgery in rhinology, for the endoscopic pituitary surgery. METHODS: The irrigation-suction straw system (K-endosheath; Koken Co., Tokyo, Japan) consists of a flattened disposable straw catheter which can be attached on a rigid endoscope. When the endoscope is inserted into the oblong catheter, two gaps remain on either side of the endoscope. Through each of these gaps irrigation and continuous suction are performed respectively. RESULTS: Clear vision could be immediately obtained by pressing the button to release the irrigation water onto the endoscope's front lens. Even targeted irrigation during drilling was possible. Above all, continuous suction was useful to clear the operative field of blood, smoke, or bone dust, ensuring the safety and uninterrupted progress of the procedure. CONCLUSION: This irrigation-suction system has proved to be very useful and easy to use for endonasal endoscopic pituitary surgery. Further development of such new devices and instruments specialized for endonasal endoscopic pituitary surgery will promote the increased use of this minimally invasive technique in neurosurgery.

Blood↗

Sensitivity of adult T-cell leukaemia lymphoma cells to tumour necrosis factor-related apoptosis-inducing ligand.

Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis in many transformed cells, but not in normal cells, and hence TRAIL has recently emerged as a novel anti-cancer agent. Adult T-cell leukaemia lymphoma (ATLL) is a neoplasm of T-lymphocyte origin aetiologically associated with human T-lymphotropic virus type 1 (HTLV-I), and is resistant to standard anti-cancer therapy. We thus characterized the sensitivity of ATLL cells to TRAIL in this study. Although most primary ATLL cells and cell lines expressed TRAIL death receptors on their surface, they showed only restricted sensitivity to TRAIL. Among the 10 ATLL cell lines examined, one was sensitive, but two had insufficient death-receptor expression, two had an unknown resistant mechanism with abrogation of the death signal upstream of caspase-8, and the remaining five showed attenuation of the signal in both extrinsic and intrinsic pathways by X-linked inhibitor of apoptosis and Bcl-2/Bcl-xL respectively. Furthermore, the level of HTLV-I tax expression was significantly correlated to TRAIL resistance. Interestingly, ATLL cells themselves expressed TRAIL on the cell surface. Constitutive production of TRAIL may offer resistance, thus allowing the development of TRAIL-resistant ATLL cells. Consequently, the resistant mechanism in ATLL cells against TRAIL was assigned to multiple factors and was not explained by a definitive single agent.

Antineoplastic Agents↗

Proviral status of HTLV-1 integrated into the host genomic DNA of adult T-cell leukemia cells.

Human T-cell leukemia virus type-1 (HTLV-1) is the etiological agent of adult T-cell leukemia (ATL), and leukemic cells always carry the proviral genome monoclonally integrated into their host genomes at the same sequence site, designated as the monoclonal integration. Using Southern blot hybridization (SBH) and sequenced tagged site polymerase chain reaction assays, we examined the proviral status in 558 clinical specimens from 350 patients who are suspected to have ATL. A total of 321 specimens (57.5%) from 241 patients showed positive results for the monoclonal integration according to SBH, using EcoR1 and Pst1. The 241 patients consisted of 136 patients (56.4%) with the complete provirus (C-type), 62 patients (25.7%) with a defective provirus (D-type), and 43 patients (17.8%) with multibands (M-type). The incidence of the D- and M-types were in the order of smoldering, chronic, and acute subtypes of ATL, suggesting that such an aberrant proviral status is generated on the way to multistep carcinogenesis and is subsequently clinically important for the malignant behavior of the disease. Moreover, our data showed that the partial deletion of the proviral genome is initiated first at the site of the gag region and spreads into the sites of the pol and env regions, whereas the long terminal repeats and pX regions are almost always conserved. These results suggest that analysis of the proviral status provides useful diagnostic and virologic-oncological information about ATL and HTLV-1 pathology, especially the important role of pX gene in tumorigenesis.

Adult↗

Long-term outcome of per anum intersphincteric rectal dissection with direct coloanal anastomosis for lower rectal cancer.

OBJECTIVE: The authors have performed per anum intersphincteric rectal dissection. With direct coloanal anastomosis for cases of lower rectal cancer in which the distal surgical margin is difficult to secure by the double stapling technique. The aim of this study was to evaluate the long-term outcome and to clarify the surgical indications for this operation. PATIENTS AND METHODS: Between 1993 and 2002, 31 patients underwent per anum intersphincteric rectal dissection with direct coloanal anastomosis. Of these, two patients (one stage 0 and one stage IV) were excluded from the analysis of oncological outcome. The remaining 29 patients formed the basis of this study. The median follow-up was 57 months (range 6-106 months). RESULTS: Local recurrence and distant metastasis developed in 9 and 3 patients, respectively. Local recurrence rate for pT1 was significantly lower than that for pT2/T3 disease. The local recurrence rate cases with tumours less than 3 cm was significantly lower than that for tumours sized 3 cm or more. The distant metastasis rate for cases with lymph node metastasis was significantly higher than that for cases without lymph node metastasis. There was an association between distant metastasis and TNM or pT stage. The overall survival rates for stage I, II and III were 85%, 80% and 89%, respectively. No significant difference was seen in total Cleveland Clinic incontinence score between per anum intersphincteric rectal dissection with direct coloanal anastomosis and the double stapling technique. CONCLUSION: The surgical indications of this operation should be limited to patients with T1 rectal cancer or tumours less than 3 cm.

Adult↗