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Boron neutron capture therapy (BNCT) with p-boronophenylalanine (BPA) is expected to have less effect on the decrease in normal bone strength than X-ray therapy. However, the compound biological effectiveness (CBE) value necessary to convert the boron neutron capture reaction (BNCR) dose into a bioequivalent X-ray dose has not been determined yet. The purpose of this study was to evaluate the influence of BNCT on normal bone in mice and to elucidate the CBE factor. We first searched the distribution of BPA in the normal bone of C3H/He mice and then measured the changes in bone strength after irradiation. The CBE value was determined when the decrease in bone strength was set as an index of the BNCT effect. The 10B concentrations in the tibia after subcutaneous injection of 125, 250 and 500 mg/kg BPA were measured by prompt gamma-ray spectroscopy and inductively coupled plasma (ICP)-atomic emission spectrometry. The 10B mapping in the tibia was examined by alpha-track autoradiography and laser ablation-ICP-mass spectrometry. The 10B concentration increased dose-dependently; moreover, the concentrations were maintained until 120 min after BPA administration. The administered 10B in the tibia was abundantly accumulated in the growth cartilage, trabecular bone and bone marrow. The bone strength was analyzed by a three-point bending test 12 weeks after irradiation. The bending strength of the tibia decreased dose-dependently after the irradiation of X-ray, neutron and BNCR. The CBE factor was obtained as 2.27 by comparing these dose-effect curves; the value determined in this study will enable an accurate dosimetry of normal bone., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Boron neutron capture therapy is a cellular-scale heavy-particle therapy. The factor determining the biological effects in the boron neutron capture reaction (BNCR) is the value of ${\alpha}_{boron}$, which is the alpha component in the Linear Quadratic (LQ) model. Recently, the factor determining the value of ${\alpha}_{boron}$ has been revealed to correspond to the structural features of the tumor tissue. However, the relationship and mechanism have yet to be thoroughly studied. In this study, we simulated BNCR in tissues using the Monte Carlo simulation technique and examined the factors that determine the value of ${\alpha}_{boron}$. According to this simulation, the nuclear-cytoplasmic (N/C) ratio, nuclear diameter and heterogeneity of the distribution of boron in the tissue have been suggested to determine the value of ${\alpha}_{boron}$. Moreover, we proposed Biological Effectivity (BE) as a new dosimetry index based on the surviving fraction (SF), extending the concept of absolute biological effectiveness (ABE) in a previous report., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

The present study aimed to analyze treatment outcomes after induction chemotherapy followed by chemoradiotherapy (CRT) using volumetric-modulated arc therapy (VMAT) in patients with stage IVA-B oropharyngeal cancer (OPC) or hypopharyngeal cancer (HPC), with long-term observation, including examination of larynx preservation. A total of 60 patients with stage IVA-B OPC or HPC, who underwent induction TPF chemotherapy (a combination regimen consisting of docetaxel, cisplatin, and 5-fluorouracil) followed by CRT using VMAT were analyzed. Overall survival (OS), progression-free survival (PFS), laryngoesophageal dysfunction-free survival (LEDFS), and locoregional control (LRC) were calculated and compared. Univariate and multivariate analyses were performed to determine statistical differences in OS and LEDFS. The median follow-up period at the time of evaluation was 61 months. Twenty-six (43%) patients had OPC and 34 (57%) had HPC. The 5-year OS, PFS, LEDFS, and LRC rates were 57%, 52%, 52%, and 68%, respectively. Response to TPF therapy was the only significant predictive factor of OS and LEDFS in multivariate analyses. Regarding long-term toxicities, grade ≥ 2 late toxicities accounted for 15%. No patients experienced grade ≥ 3 xerostomia, and 5% of all patients developed grade 3 dysphagia. With long-term observation, the OS, PFS, and LEDFS rates were relatively good, and the incidence of late toxicities was low. TPF followed by CRT using VMAT was feasible and more effective in those who responded to induction chemotherapy., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Auxin and cytokinin control callus formation from developed plant organs as well as shoot regeneration from callus. Dedifferentiation and regeneration of plant cells by auxin and cytokinin stimulation are considered to be caused by the reprogramming of callus cells, but this hypothesis is still argued to this day. Although an elucidation of the regulatory mechanisms of callus formation and shoot regeneration has helped advance plant biotechnology research, many plant species are intractable to transformation because of difficulties with callus formation. In this study, we identified fipexide (FPX) as a useful regulatory compound through a chemical biology-based screening. FPX was shown to act as a chemical inducer in callus formation, shoot regeneration and Agrobacterium infection. With regards to morphology, the cellular organization of FPX-induced calli differed from those produced under auxin/cytokinin conditions. Microarray analysis revealed that the expression of approximately 971 genes was up-regulated 2-fold after a 2 d FPX treatment compared with non-treated plants. Among these 971 genes, 598 genes were also induced by auxin/cytokinin, whereas 373 genes were specifically expressed upon FPX treatment only. FPX can promote callus formations in rice, poplar, soybean, tomato and cucumber, and thus can be considered a useful tool for revealing the mechanisms of plant development and for use in plant transformation technologies.

Purpose: The present study examined the clinicopathological impact of survivin expression in oesophageal squamous cell carcinoma (ESCC). In addition, the biological role of anti-apoptosis parameter in ESCC was examined immunohistochemically., Patients and Method: Subjects comprised 71 patients followed up for 5 years after surgery for ESCC and analysed immunohistochemically to examine the clinicopathological impact of survivin expression. Separately, 37 fresh frozen samples of ESCC obtained recently were examined concerning splicing variant expression of survivin using reverse-transcription polymerase chain reaction (RT-PCR)., Results: Immunohistochemical survivin expression was detected in the nuclei of 10 ESCC specimens (14.1%) and cytoplasm of 22 specimens (31.0%). Nuclear expression displayed no clinicopathological implications, but cytoplasmic expression correlated with histological differentiation (p=0.002) and tumour invasion (p=0.073) and showed prognostic impacts in univariate (p=0.0184) and multivariate (p=0.0299) analyses. Survivin, survivin-2B and survivin-deltaEx3 mRNA were amplified in 31 (83.8%), 23 (62.2%) and 26 (70.3%) specimens, respectively, by RT-PCR. Survivin-2B level related significantly with histological differentiation (p=0.038), but no other significant implication was identified between any mRNA and clinicopathological factors., Conclusion: As a molecular biological anti-apoptotic factor, survivin expression was of use in assessing prognosis in ESCC. Inhibition of survivin may be useful as a molecular biological therapy in ESCC., (Copyright 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.)

Natural polyisoprene is a biopolymer consisting of isoprene units (C(5)H(8)) that is used commercially in household, medical, and industrial materials. For the management of natural polyisoprene production, the selection of high-yield polyisoprene-producing trees, and an understanding of polyisoprene biosynthesis, a high-throughput and highly sensitive screening method for the quantification of polyisoprene is required. In this study, we examined pyrolysates from polyisoprenes, polyprenols, carotenoids, ubiquinone (CoQ-10), and sterols by pyrolysis gas chromatography/mass spectrometry (PyGC/MS) and determined that the amounts of isoprene and limonene released from polyprenols and polyisoprenes were dependent upon their molecular weights. Based on these results, we developed a relative quantification method for polyisoprene in leaves by direct analysis of 1 mg of leaves using PyGC/MS. This novel quantification method eliminated extraction steps and can be used in the measurement of polyisoprene contents in Eucommia ulmoides and Hevea brasiliensis.

Mutagenized cell libraries of Corynebacterium glutamicum were screened for mutants that lost the ability to grow under low oxygen concentrations. The resulting high-oxygen-requiring mutants were used to clone wild-type DNA fragments that could complement the phenotype. Sequencing and subcloning analyses identified six genes, Cgl0807, Cgl1102, Cgl0600, Cgl1427, Cgl2857, and Cgl2859, as the genes responsible for complementation. Some of these genes showed cross-complementation of the mutants in oxygen-limiting static culture, suggesting the utility of these genes for improved growth and production under oxygen limitation.

Natural rubber is synthesized as rubber particles in the latex, the fluid cytoplasm of laticifers, of Hevea brasiliensis. Although it has been found that natural rubber is biosynthesized through the mevalonate pathway, the involvement of an alternative 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway is uncertain. We obtained all series of the MEP pathway candidate genes by analyzing expressed sequence tag (EST) information and degenerate PCR in H. brasiliensis. Complementation experiments with Escherichia coli mutants were performed to confirm the functions of the MEP pathway gene products of H. brasiliensis together with those of Arabidopsis thaliana, and it was found that 1-deoxy-D-xylulose-5-phosphate reductoisomerase, 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase, and 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase of H. brasiliensis were functionally active in the E. coli mutants. Gene expression analysis revealed that the expression level of the HbDXS2 gene in latex was relatively high as compared to those of other MEP pathway genes. However, a feeding experiment with [1-(13)C] 1-deoxy-D-xylulose triacetate, an intermediate derivative of the MEP pathway, indicated that the MEP pathway is not involved in rubber biosynthesis, but is involved in carotenoids biosynthesis in H. brasiliensis.

The purpose of this study was to analyze loss of p16 expression and its relationship to hypermethylation, clinicopathological parameters and prognosis in patients with esophageal squamous cell carcinoma (ESCC). Tissue samples from 60 ESCC were subjected to histological analysis. Immunohistochemical staining for p16 expression was performed. DNA was extracted from these primary esophageal tumors and from sera from another 38 ESCC patients. The DNA was modified with bisulfite and analyzed for p16 promoter methylation by methylation-specific polymerase chain reaction. Twelve out of the 60 tumors (20%) were methylated at the p16 promoter and 48 tumors (80%) were unmethylated. There were no significant correlations between the methylation of the p16 promoter and clinicopathological parameters. Immunohistochemical staining revealed that 41 of the 60 tumors (68.3%) were p16-negative and 19 tumors (31.7%) were p16-positive. The correlation between negative p16 immunohistochemical staining and methylation was statistically significant (P = 0.0084). No instances of p16 methylation and p16 positive immunostaining were found. There was a close correlation between loss of p16 expression and poorer prognosis in ESCC (P = 0.0517 in overall survival, P = 0.0478 in disease-free survival). The p16 gene promoter hypermethylation was detected in the serum of two of 38 (5.2%) patients with ESCC. This indicates that p16 promoter methylation suppresses p16 expression and that the loss of expression has a close relationship with poor prognosis in patients with ESCC. The present results may lead to the development of new therapeutic strategies, such as p16(INK4A) gene therapy, to treat patients with ESCC.

We used immunohistochemical analysis to study the expression and prognostic impact of cyclin B1, a key molecule for G2-M phase transition during the cell cycle, in a series of 342 curatively resected colorectal carcinomas. In 269 tumors (78.7%), high expression of cyclin B1 in more than 10% of tumor cells was observed, but there was no association between cyclin B1 expression and histopathologic tumor features. Univariate analysis revealed no impact on disease-free and overall survival. Multivariate analysis revealed pT and pN categories, extramural blood vessel invasion, and low-grade tumor cell differentiation as independent prognostic predictors for overall survival, and pT and pN categories and tumor site for disease-free survival. According to our results, high expression of cyclin B1 is a frequent and early event in colorectal carcinomas. However, cyclin B1 expression is neither a predictor of prognosis in patients with colorectal cancer nor a suitable tool for identifying subgroups of patients at higher risk for disease recurrence.

Feeding experiments were independently performed with [1-13C]deoxy-D-xylulose triacetate and (RS)-[2-13C]mevalonolactone in the tobacco plant. The labeling pattern for solanesol was elucidated to reveal that the isoprene moiety of solanesol would be derived from deoxy-xylulose. The result strongly suggests that tobacco solanesol is biosynthesized via the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway.

Hypermethylation in the E-cadherin promoter region and expression of the transcription factor Snail were analyzed in 41 cases of esophageal squamous cell carcinoma (ESCC) and paired normal squamous epithelium by methylation-specific polymerase chain reaction (PCR) and reverse transcription-polymerase chain reaction (RT-PCR) to clarify the mechanism regulating E-cadherin deletion; 93 cases of ESCC were analyzed immunohistochemically to determine the clinicopathologic impact of E-cadherin deletion. Hypermethylation of the E-cadherin promoter and Snail overexpression were detected in 25 cases (61%) by methylation-specific PCR and 34 cases (83%) by RT-PCR, respectively. Reduced E-cadherin expression, observed immunohistochemically in 55 cases (59%), correlated with hypermethylation (P = .0011) but not Snail overexpression (P = .685). Hypermethylation and Snail overexpression correlated significantly with E-cadherin deletion (P = .0018). Snail overexpression was unrelated to clinicopathologic factors. Reduced E-cadherin expression correlated with tumor invasion (P = .019) and vascular invasion (P = .052) but not other factors. E-cadherin deletion had prognostic impact in univariate (P = .023) and multivariate (P = .034) analyses. E-cadherin deletion was regulated by hypermethylation and Snail expression. Examination of reduced E-cadherin expression is important for assessing biologic behavior, including clinical outcome, in patients with ESCC.

The oil-producing fungus Mortierella alpina 1S-4 is an industrial strain. In order to prepare host strains for a transformation system for this fungus, six uracil auxotrophs were obtained by means of random mutation with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). When the activities of orotate phosphoribosyl transferase (OPRTase, EC 2.4.2.10) and orotidine-5'-phosphate decarboxylase (OMPdecase, EC 4.1.1.23) were examined in the mutants and wild strain, OPRTase activity was found to be completely absent in all mutants, on the other hand, OMPdecase activity was intact. The genomic DNA and cDNA of the ura5 gene encoding OPRTase and the ura3 gene encoding OMPdecase were cloned and sequenced. The Ura5p deduced amino acid sequence of this fungus showed highest similarity to that of Vibrio cholerae classed among prokaryote. Furthermore, the mutational points in the ura5 genes of two selected mutants were identified; a base-replacement and a base-insertion.

Aggressive surgery including extensive lymph node dissection is considered necessary to improve the long-term survival of patients with esophageal carcinoma. While three-field lymph node dissection is widely performed for patients with thoracic esophageal carcinoma, cervical lymph node metastasis is uncommon. In order to reduce surgical stress, we have developed a two-step three-field lymph node dissection procedure for thoracic esophageal carcinoma. In the first-step operation, total thoracic esophagectomy through a right thoracotomy is performed. Mediastinal and abdominal lymph node dissection is performed synchronously. When recurrent nerve lymph node metastasis is pathologically positive, cervical lymph node dissection is performed about 3 weeks after the first operation (second step). Of 343 patients with carcinoma of the esophagus surgically treated in our department between 1990 and 2001, 146 underwent the operation described above. Three-field dissection was performed in 68 patients (group A), while two-field dissection was performed in 78 patients (group B). In the 68 group A patients, cervical lymph node metastasis was positive in 15 patients (22%). There was no marked difference in the onset of major complications between the two groups. The 5-year survival rate was 58% for group A and 61% for group B, not a statistically significant difference. In 78 of the 146 patients, it was possible to avoid cervical lymph node dissection without negatively affecting therapeutic outcomes. Two-step three-field lymph node dissection can reduce surgical stress of patients with good clinical outcome., (Copyright 2004 ISDE)

Reconstruction of cervical esophagus and hypopharynx following cervical esophagectomy and laryngopharyngectomy is generally performed using jejunal autograft interposition. However, this method has some disadvantages and is not suitable for optimal swallowing function. In our institution, free transverse colonic graft has been successfully applied for reconstructive purposes in 12 cases since 1986. The present report describes a case of upper esophageal web accompanying superficial squamous cell carcinoma and details the operative techniques utilized.

Pyrimidine nucleoside phosphorylase (PyNPase) converts 5'-deoxy-5-fluorouridine to 5'-fluorouracil, which exerts an anticancer effect before being catabolized by dihydropyrimidine dehydrogenase (DPD). Recently, PyNPase has been shown to be identical to a potent angiogenic factor, platelet-derived endothelial cell growth factor. We analyzed the concentration of PyNPase and DPD in 33 patients with esophageal squamous cell carcinoma in fresh-frozen samples by enzyme-linked immunosorbent assay. In addition, we evaluated the clinical significance and prognostic value of PyNPase expression in esophageal carcinoma. The PyNPase concentration of tumor tissue was statistically higher than that of normal tissue of the esophagus (248 +/- 146 U/mg protein vs 73 +/- 63 U/mg protein, P = 0.0001), whereas DPD showed no difference (90 +/- 62 U/mg protein vs 88 +/- 62 U/mg protein, P = 0.825). The ratio of PyNPase to DPD of tumor tissue was statistically higher than that of normal tissue of the esophagus (3.3 vs 0.95, P = 0.0001). There were no significant differences between the group with high tumor to normal tissue ratios of PyNPase concentration and the low-ratio group in terms of the tumor length, depth, lymph node metastasis, lymph vessel invasion, vascular invasion, stage and survival. In conclusion, 5'-deoxy-5-fluorouridine may be effective on esophageal carcinoma and PyNPase concentration in esophageal carcinoma may not be a useful prognostic marker for patients with esophageal squamous cell carcinoma.

We present the case of a 26-year-old woman who underwent a successful laparoscopic resection of an esophageal duplication cyst without any other congenital abnormalities. Although computed tomography (CT) scan and endoscopic ultrasonography (EUS) both assisted in determining the correct preoperative diagnosis, the definitive diagnosis was made following pathological examination of the resected lesion.

Apoptosis is one of the critical biological factors that correlate with the biological behavior of malignant tumors including cancer progression and clinical outcome. The present study was performed to clarify the clinical implications of BAG-1, a bcl-2 binding protein in esophageal squamous cell carcinoma (ESCC). Seventy-one cases with ESCC were investigated. Immunohistochemical study of BAG-1 was performed on resected specimens. The expression pattern of BAG-1 in nuclei and/or cytoplasm was analyzed and correlated with TNM classification, vessel invasion, survival period after surgery. BAG-1 expression in the nuclei was related to the depth of tumor invasion (P = 0.0381) but not to any other clinicopathologic parameters. The cytoplasmic staining pattern of BAG-1 exhibited no correlation with clinicopathologic parameters. Univariate analysis (P < 0.05), but not multivariate analysis, revealed significantly poor prognosis for ESCC cases exhibiting positive nucleic staining for BAG-1. Our data suggests that BAG-1 expression in the nuclei of ESCC plays an important role in tumor development and may be useful for predicting the prognosis after surgery.

Small cell carcinoma arising in the esophagus is a relatively rare disease. In the more common small cell carcinoma of the lung, the diagnostic significance of several new markers has been recently reported. This study used immunohistochemical techniques in addition to clinicopathological analysis, in order to clarify the utility of newer markers as biological parameters or as diagnostic tools. Six patients with small cell carcinoma of the esophagus were clinicopathologically analyzed. Immunohistochemical staining was performed using primary antibodies for bombesin, CD56 and CD57 in addition to conventional endocrine markers chromogranin A, neuron specific enolase and synaptophysin. All patients died within 2 years of surgery due to cancer recurrence, whether or not they had received adjuvant therapy. Pathological stages ranged from IIa to IVb and lymph node metastasis was observed in five cases. Of the six cases, four showed a positive reaction for bombesin and five were positive for CD57. In contrast, no cases revealed a positive reaction for CD56. The one case to survive 24 months after surgery was not shown to express bombesin, CD56 or CD57. Small cell carcinoma of the esophagus demonstrated an unfavorable prognosis. The study suggested that in this disease, bombesin and CD57 (but not CD56) were useful as biological markers, predicting clinical outcome rather than having diagnostic significance.

The prognosis of patients with T4 esophageal carcinoma is poor, and thus an effective treatment needs to be established. The present study assessed the effect of chemoradiotherapy (CRT), postoperative morbidity and mortality, and survival time in 41 patients with T4 esophageal carcinoma. Of these, 24 received CRT followed by surgery (group A) and the remaining 17 were treated with CRT alone (group B). Postoperative complications in group A were compared with 251 patients (group C) who underwent surgery without CRT during the same period. Postoperative complications were more frequent in group A than group C (29.2% vs 8.4%, P < 0.05). The overall median survival of group A was statistically longer than that of group B (13.8 months and 3.3 months respectively, P < 0.001). Complete histologic response (grade 3) was documented in 4 group A patients (16.7%). The overall median survival of grade 3 patients was statistically longer than the rest of group A (38.9 months vs 8.8 months, P < 0.05). The data confirm that chemoradiotherapy creates tumor regression in some patients and allows resection surgery in T4 esophageal carcinoma. Moreover, surgery with CRT confers a survival advantage in T4 esophageal carcinoma.

Recently, neoadjuvant chemotherapy combined with radiation (NAT) has been used in the active treatment of progressive esophageal cancer (T4). However, many patients are resistant to supplemental therapy, and it is necessary to to be aware that side-effects may occur. Accordingly, to minimize adverse reactions and cost, it is important to determine the indications for NAT. We investigated 34 patients with T4 esophageal squamous cell carcinoma and examined the relation between the effects of NAT and immunohistochemical or additional clinicopathologic factors. There was no relation between clinicopathologic factors and immunohistochemical findings (p53 or hsp27 expression), and no clinicopathologic factors showed a relation to a supplemental therapeutic effect. In addition, there was no correlation between p53 staining and therapeutic effects (P=0.734). In contrast, there was a correlation (P=0.0058) between hsp27 staining and therapeutic effect. In conclusion, the usefulness of hsp27 immunostaining in predicting the therapeutic effect of NAT was confirmed in T4 esophageal squamous cell carcinoma.

Several acetic acid bacteria of the genus Acetobacter oxidize much acetate oxidation, which is not desired in vinegar manufacturing. Acetobacter rancens SKU 1111, a strong acetate oxidant, grew rapidly with a biphasic growth curve while consuming acetate in the second growth phase. Acetobacter aceti IFO 3284 did not show extensive acetate oxidation. Addition of glycerol to the culture medium of Acetobacter rancens SKU 1111 increased acetate oxidation and resulted in more biomass in the second growth phase than when glycerol was not added. Enzyme activities of acetyl-CoA synthetase and phosphotransacetylase in the organism were high during acetate oxidation. The activity of phosphoenolpyruvate carboxylase was most stimulated by a trace amount of acetyl-CoA among the enzymes of glycerol catabolism. Phosphoenolpyruvate carboxylase in A. rancens SKU 1111 showed a sigmoidal saturation curve with acetyl-CoA. This finding suggested that strong acetate oxidation caused by acetyl-CoA synthetase or phosphotransacetylase activity, together with phosphoenolpyruvate carboxylase, increased the biomass.