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For total laparoscopic distal gastrectomies for gastric cancer, the reconstruction method is critical to the clinical outcome of the procedure. However, which reconstruction technique is optimal remains controversial. We originally reported the augmented rectangle technique (ART) as a reconstruction option for total laparoscopic Billroth I reconstructions. Still, little is known about its effect on long-term outcomes, specifically the incidence of postgastrectomy syndrome and its impact on quality of life.To analyze postgastrectomy syndrome and quality of life after ART using the Postgastrectomy Syndrome Assessment Scale-37 (PGSAS-37) questionnaire.At Juntendo University, a total of 94 patients who underwent ART for Billroth I reconstruction with total laparoscopic distal gastrectomies for gastric cancer between July 2016 and March 2020 completed the PGSAS-37 questionnaire. Multidimensional analysis was performed, comparing those 94 ART cases from our institution (ART group) to 909 distal gastrectomy cases with a Billroth I reconstruction from other Japanese institutions who also completed the PGSAS-37 as part of a larger national database (PGSAS group).Patients in the ART group had significantly better total symptom scores in all the symptom subscales (ART for Billroth I reconstruction provided beneficial long-term results for postgastrectomy syndrome and quality of life in patients undergoing total laparoscopic distal gastrectomies for gastric cancer.

Aim: The transorally inserted anvil (OrVilTM) is often selected for esophagojejunostomy after total laparoscopic gastrectomy due to its versatility. During anastomosis with OrVilTM, it is possible to select a double stapling technique (DST) or a hemi-double technique (HDST) by overlapping the linear stapler and the circular stapler, although there has been no report on the anastomotic strength. Thus, an animal experiment was conducted and verified this study. Methods: This experiment used 10 fresh porcine esophageal and jejunal specimens. Two models were created: a model in which the rod is placed at the center of the esophageal transection line (DST model) and a model in which the rod is placed at the lateral end of the esophageal transection line (HDST model). A pressure gage was inserted into the anastomosed intestine while continuously measuring pressure to determine the leakage site and leakage pressure. Results: The leakage site in both the DST (n = 5) and HDST models (n = 5) were at the staple overlapping with a leakage pressure of 151.2 ± 14.2 mmHg in the DST model and 148.2 ± 6.3 mmHg in the HDST model (P = 0.678). When the leakage site was repaired with hand-sewn sutures and conducted remeasuring pressure, leakage was observed from the contralateral crossing in the DST model and the leakage pressure was 155.8 ± 12.2 mmHg. In the HDST model, all models were capable of withstanding 300-mmHg pressures. Conclusion: HDST with a single staple intersection is beneficial for esophagojejunostomy, in terms of pressure resistance, and the repairing suture at the staple intersection can increase pressure resistance.

Diffusely infiltrative esophageal squamous cell carcinoma is so rare that very few studies have been reported. Therefore, it has not been clear whether the survival of patients with this disease is poor or not. In this study, we retrospectively investigated our long-term results of radical esophagectomy for patients with diffusely infiltrative esophageal squamous cell carcinoma in our institution. In addition, we tried to detect prognostic factors of this disease if possible. Data were retrospectively collected from medical records. Eligible patients underwent esophagectomy for esophageal squamous cell carcinoma with diffuse infiltration from 2002 to 2018 in our institution. Diagnosis of this disease was done in the conference of esophageal surgical team based on the findings of endoscopy and upper gastrointestinal series. Overall survival rates were calculated by the Kaplan–Meier method, and statistical significance was determined by the log-rank. P value of 32 patients were selected in this study. Median age was 66 years old, cStage I/II/III/IV was 0/10/14/8 patients respectively, preoperative treatment was undergone for 11 patients. 5-year overall survival (OS) rate was 27.3% and 3-year OS rate was 37.5%. 5-year OS rate for each cStage II/III/IV was 48.0%, 14.3% 25.0%. Patients who underwent preoperative treatment seemed to have poor prognosis with statistically significant difference. Patients with clinical or pathlogical supraclavicular lymph node metastasis tended to have poor prognosis. In this study, about 20% patients could obtain long-term survival. Therefore, surgical intervention could be one of the treatments for the patient with this disease. And also, we may take into account the postoperative treatment for the patient with poor prognostic factor.

Background: Gastric cancer (GC) is the second most common cancer in Japan in terms of incidence and the third most common in terms of deaths. The onset and progression of cancer are generally suppressed by the action of immune cells, which is an inflammatory response. MDSCs are thought to promote cancer progression and invasion by suppressing the function of immune cells, making them potential therapeutic and diagnostic targets. We measured MDSCs in GC patients and observed more monocyte-derived MDSCs in peripheral blood in advanced GC than in early GC. However, granulocyte-derived MDSCs showed no difference in GC progression when markers for classical MDSCs were used. We considered that granulocyte-derived MDSCs were much more abundant than monocyte-derived MDSCs in peripheral blood and were involved in cancer progression. We hypothesized that we had a new granulocyte-derived marker for advanced GC that did not show differences in classical markers, but may have different functions, and aimed to identify a novel subset that may be a therapeutic and diagnostic target. Method: For GC patients, we used heparin blood samples provided by patients who consented to Juntendo University. We analyzed the expression of various cell surface proteins against populations of CD33high, CD66bhigh, and HLA-DRlow as classical markers of MDSCs derived from granulocytes of GC patients using FACS (Melody). MDSCs were isolated by a cell sorter and used for experiments such as RNA-Seq. Novel markers and involved cytokines were quantified in plasma components by cytometric bead array. Result: The chemokine receptors CCR2, CCR5, CXCR4, and CXCR5 were highly expressed in MDSCs of advanced GC patients. The ability to suppress T-cell activation was also found to be stronger in MDSCs with advanced GC. In addition, IL-10 produced by MDSCs was also more abundant in the plasma of patients with advanced GC, as well as chemokines according to chemokine receptors. Conclusion: The high expression of chemokine receptors on MDSCs in advanced GC may indicate that chemokines produced at the cancer site facilitate the migration of MDSCs. These novel subsets of MDSCs found in advanced GC suggest that they may be new therapeutic targets. Citation Format: Suguru Yamauchi, Takumi Iwasawa, Tomoaki Ito, Malcom V. Brock, Tetsu Fukunaga, Hajime Orita, Kazunori Kato. Analysis of MDSCs as a diagnostic and therapeutic target for gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5958.

The development and progression of cancers are frequently promoted by immunosuppressive cells, such as Treg and myeloid-derived suppressor cells (MDSCs) mediated by various immune checkpoint molecules. Recently, the immune checkpoint inhibitor anti-PD-1 neutralizing antibody has become available for the first-line treatment of gastric cancer (GC) in Japan. However, there is no correlation between PD-1 or PD-L1 expression in Treg or GC tissues and clinical responses to anti-PD-1 antibody. MDSCs are immature myeloid cells thought to suppress immune cell action, but the functional cell surface markers that define MDSCs correlated with cancer progression has not yet been clarified well. In this study, we identified a new subset of potential therapeutic and diagnostic targets for MDSCs in GC patients. Significantly higher levels of immune checkpoint molecules, PD-1 and PD-L1, were expressed on granulocytic MDSCs from advanced than early-stage of GC patients. Interestingly, we found that a subset of G-MDSCs expressed not only PD-1 but also PD-L1 and the pretreatment of G-MDSCs with anti-PD-1 antibody ameliorated T cell responses in vitro. We also found that G-MDSCs isolated from patients treated with anti-PD-1 antibody had a lower ability to suppress T cells. These data indicate that a novel subset of G-MDSCs expressing PD-1 found in advanced GC could be novel therapeutic targets. Citation Format: Takumi Iwasawa, Suguru Yamauchi, Tetsu Fukunaga, Hajime Orita, Kazunori Kato. Novel subset of granulocytic MDSCs as immunosuppressive regulators and therapeutic targets in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2889.

BACKGROUND Total laparoscopic distal gastrectomy (TLDG) is increasing due to some advantages over open surgery, which has generated interest in gastrointestinal surgeons. However, TLDG is technically demanding especially for lymphadenectomy and gastrointestinal reconstruction. During the course of training, trainee surgeons have less chances to perform open gastrectomy compared with that of senior surgeons. AIM To evaluate an appropriate, efficient and safe laparoscopic training procedures suitable for trainee surgeons. METHODS Ninety-two consecutive patients with gastric cancer who underwent TLDG plus Billroth I reconstruction using an augmented rectangle technique and involving trainees were reviewed. The trainees were taught a laparoscopic view of surgical anatomy, standard operative procedures and practiced essential laparoscopic skills. The TLDG procedure was divided into regional lymph node dissections and gastrointestinal reconstruction for analyzing trainee skills. Early surgical outcomes were compared between trainees and trainers to clarify the feasibility and safety of TLDG performed by trainees. Learning curves were used to assess the utility of our training system. RESULTS Five trainees performed a total of 52 TLDGs (56.5%), while 40 TLDGs were conducted by two trainers (43.5%). Except for depth of invasion and pathologic stage, there were no differences in clinicopathological characteristics. Trainers performed more D2 gastrectomies than trainees. The total operation time was significantly longer in the trainee group. The time spent during the lesser curvature lymph node dissection and the Billroth I reconstruction were similar between the two groups. No difference was found in postoperative complications between the two groups. The learning curve of the trainees plateaued after five TLDG cases. CONCLUSION Preparing trainees with a laparoscopic view of surgical anatomy, standard operative procedures and practice in essential laparoscopic skills enabled trainees to perform TLDG safely and feasibly.

Background Replication-competent adenoviruses (Ad) produced cytotoxic effects on infected tumors and have been examined for the clinical applicability. A biomarkers to predict the cytotoxicity is valuable in a clinical setting. Methods We constructed type 5 Ad (Ad5) of which the expression of E1A gene was activated by a 5′ regulatory sequences of survivin, midkine or cyclooxygenase-2, which were highly expressed in human tumors. We also produced the same replication-competent Ad of which the fiber-knob region was replaced by that of Ad35 (AdF35). The cytotoxicity was examined by a colorimetric assay with human tumor cell lines, 4 kinds of pancreatic, 9 esophageal carcinoma and 5 mesothelioma. Ad infectivity and Ad-mediated gene expression were examined with replication-incompetent Ad5 and AdF35 which expressed the green fluorescence protein gene. Expression of cellular receptors for Ad5 and AdF35 was also examined with flow cytometry. A transcriptional activity of the regulatory sequences was investigated with a luciferase assay in the tumor cells. We then investigated a possible correlation between Ad-mediated cytotoxicity and the infectivity/gene expression, the transcriptional activity or the p53 genotype. Results We found that the cytotoxicity was greater with AdF35 than with Ad5 vectors, but was not correlated with the Ad infectivity/gene expression irrespective of the fiber-knob region or the E1A-activating transcriptional activity. In contrast, replication-competent Ad produced greater cytotoxicity in p53 mutated than in wild-type esophageal carcinoma cells, suggesting a possible association between the cytotoxicity and the p53 genotype. Conclusions Sensitivity to Ad-mediated cytotoxic activity was linked with the p53 genotype but was not lineally correlated with the infectivity/gene expression or the E1A expression. Electronic supplementary material The online version of this article (10.1186/s12885-017-3621-x) contains supplementary material, which is available to authorized users.

Two DyIII complexes with same N6O3 donor atoms but different donor atom arrangements ‘fac’-[DyIII(HLDL-ala)3]·8H2O (1) and ‘mer’-[DyIII(HLDL-phe)3]·7H2O (2) were synthesized, where H2LDL-ala and H2LDL-phe are tridentate NNO ligands of N-[(imidazol-4-yl)methylidene]- dl -alanine and N-[(imidazol-4-yl)methylidene]- dl -phenylalanine, respectively. Each DyIII ion is coordinated by three mono-deprotonated mono-negative NNO tridentate ligands to form a nona-coordination geometry of a tricapped trigonal prism (TTP). 1 consists of enantiomers ‘fac’-[DyIII(HLD-ala)3] and ‘fac’-[DyIII(HLL-ala)3], while 2 consists of ‘mer’-[DyIII(HLD-phe)2(HLL-phe)] and ‘mer’-[DyIII(HLD-phe)(HLL-phe)2]. The temperature dependence of the magnetic susceptibilities and field-dependence of the magnetization of two complexes showed the different magnetic profiles and the Stark splitting of the ground state 6H15/2 due to the crystal field effect on DyIII ion (4f9, J = 15/2, S = 5/2, L = 5, gJ = 4/3, 6H15/2). Luminescence spectra were observed and the fine structures assigned to the 4F9/2 → 6H15/2 transitions are partially observed. 1 and 2 showed an out-of-phase signal with frequency-dependence in alternating current (ac) susceptibility under a dc bias field of 1000 Oe, indicative of field induced single ion magnet (SIM). The ac magnetic susceptibilities under 1000 Oe dc field of 2 showed the maximum peaks at the higher temperature than those of 1, indicating that the energy barrier of 2 is larger than that of 1.

Background The rapid expansion of laparoscopic gastrectomy (LG) for gastric cancer has generated interest among surgeons. The adequate dissemination of correct information about such advanced laparoscopic surgery can certainly be useful for surgeons and trainees. Online video resources such as YouTube are frequently used for education. This study aimed to evaluate the quality, utility, and completeness of LG videos for gastric cancer on the video website YouTube. Methods The terms "laparoscopic gastrectomy" and "gastric cancer" were searched on YouTube on August 16, 2019. The first 100 videos in three sorting categories (website's default setting, view count, and length of duration) were checked by two experienced surgeons. The popularity was evaluated with the video power index (VPI). The reliability was measured using the Journal of American Medical Association (JAMA) benchmark criteria. The educational value and completeness were evaluated with a checklist developed by the researchers. Results A total of 102 videos were analyzed. Laparoscopic distal gastrectomy (LDG) and laparoscopic total gastrectomy were the most frequently recorded techniques. Lymph node (LN) dissection was the most frequently covered topic (89.2%), followed in descending order by GI reconstruction (87.3%). The mean VPI, JAMA benchmark score and completeness score of all videos were 2.63, 1.94 and 8.53, respectively. The types of sources were as follows: private users, 73 (71.6%); academic institutions, 20 (19.6%); and others, 9 (8%). A total of 97 videos with an identifiable primary surgeon originated from eighteen different countries. Conclusions Laparoscopic videos represented by YouTube represent a useful and appropriate educational tool. However, the quality of videos varied, and the level of information incompleteness was fairly high due to insufficient reviews. The role of private uploaders and academic institutions in surgical education cannot be overestimated. It is necessary that surgeon trainers and surgical educators critically analyze the quality of video content and exercise responsibility in directing trainee surgeons. In the current era, it is best for trainees to search for peer-reviewed content.

Pancreatic carcinoma is relatively resistant to chemotherapy and cell death induced by replication of adenoviruses (Ad) can be one of the therapeutic options. Transduction efficacy of conventional type 5 Ad (Ad5) is however low and the cytotoxic mechanism by replication-competent Ad was not well understood. We constructed replication-competent Ad5 of which the E1A promoter region was replaced with a transcriptional regulatory region of the midkine, the survivin or the cyclooxygenase-2 gene, all of which were expressed at a high level in human tumors. We also prepared replication-competent Ad5 that were activated with the same region but had the type 35 Ad-derived fiber-knob region (AdF35) to convert the major cellular receptor for Ad infection from the coxsackie adenovirus receptor to CD46 molecules. Replication-competent AdF35 that were activated with the exogenous region produced cytotoxic effects on human pancreatic carcinoma cells greater than the corresponding Ad5 bearing with the same regulatory region. Cells infected with the AdF35 showed cytopathic effects and increased sub-G1 fractions. Caspase-9, less significantly caspase-8 and poly (ADP-ribose) polymerase, but not caspase-3 was cleaved and expression of molecules involved in autophagy and caspase-independent cell death pathways remained unchanged. Nevertheless, H2A histone family member X molecules were phosphorylated, and N-acetyl-L-cystein, an inhibitor for reactive oxygen species, suppressed the AdF35-mediated cytotoxicity. These data indicated a novel mechanism of Ad-mediated cell death and suggest a possible clinical application of the fiber-knob modified Ad.

Two Tb(III) complexes with the same N6O3 donor atoms but different coordination geometries, "fac"-[Tb(III)(HL(DL-ala))3]·7H2O (1) and "mer"-[Tb(III)(HL(DL-phe))3]·7H2O (2), were synthesized, where H2L(DL-ala) and H2L(DL-phe) are N-[(imidazol-4-yl)methylidene]-DL-alanine and -DL-phenylalanine, respectively. Each Tb(III) ion is coordinated by three electronically mononegative NNO tridentate ligands to form a coordination geometry of a tricapped trigonal prism. Compound 1 consists of enantiomers "fac"-[Tb(III)(HL(D-ala))3] and "fac"-[Tb(III)(HL(L-ala))3], while 2 consists of "mer"-[Tb(III)(HL(D-phe))2(HL(L-phe))] and "mer"-[Tb(III)(HL(D-phe))(HL(L-phe))2]. Magnetic data were analyzed by a spin Hamiltonian including the crystal field effect on the Tb(III) ion (4f(8), J = 6, S = 3, L = 3, gJ = 3/2, (7)F6). The Stark splitting of the ground state (7)F6 was evaluated from magnetic analysis, and the energy diagram pattern indicated easy-plane and easy-axis (Ising type) magnetic anisotropies for 1 and 2, respectively. Highly efficient luminescences with Φ = 0.50 and 0.61 for 1 and 2, respectively, were observed, and the luminescence fine structure due to the (5)D4 → (7)F6 transition is in good accordance with the energy diagram determined from magnetic analysis. The energy diagram of 1 shows an approximate single-well potential curve, whereas that of 2 shows a double- or quadruple-well potential within the (7)F6 multiplets. Complex 2 displayed an onset of the out-of-phase signal in alternating current (ac) susceptibility at a direct current bias field of 1000 Oe on cooling down to 1.9 K. A slight frequency dependence was recorded around 2 K. On the other hand, 1 did not show any meaningful out-of-phase ac susceptibility. Pulsed-field magnetizations of 1 and 2 were measured below 1.6 K, and only 2 exhibited magnetic hysteresis. This finding agrees well with the energy diagram pattern from crystal field calculation on 1 and 2. DFT calculation allowed us to estimate the negative charge distribution around the Tb(III) ion, giving a rationale to the different magnetic anisotropies of 1 and 2.

1:2 Nickel(II) complexes of 5-methylimidazol-4-yl-methylidene- l -phenylalanine (H2L l -phe) and its racemic ligand (H2L dl -phe) were synthesized and the crystal structures of the resultant [Ni(HL l -phe)2]·MeOH·3H2O (1) and [Ni(HL dl -phe)2]·6H2O (2) complexes were determined. Complex 1 crystallized in an acentrosymmetric monoclinic space group, P21 (No. 4). The nickel(II) ion is coordinated by (N2O)2 donor atoms from two tridentate H2L l -phe ligands and has an octahedral coordination environment. In the crystal, 1 contains only the l -isomer and forms a homochiral 2D structure through hydrogen bonding between the adjacent complex molecules. In contrast, Complex 2 crystallized into a centrosymmetric monoclinic space group, P21/c (No. 14). The nickel(II) ion is coordinated by (N2O)2 donor atoms from two H2L l -phe tridentate ligands. The coordination geometry around the nickel(II) ion is described as octahedral. In the crystal, 2 consists of [Ni(HL D -phe)2] and [Ni(HL l -phe)2] molecule that are related and forms a heterochiral 3D structure via hydrogen bonding through the crystal solvents.

The aggregation and luminescence properties of three pairs of Eu III ( 1 – 3 ) and isomorphous Tb III ( 4 – 6 ) complexes ligated to tripodal heptadentate N 7 ligands and bidentate acetate ion, [Eu III or Tb III (H 3 L 2-Me )(OAc)](ClO 4 ) 2 ·2MeOH·H 2 O ( 1 , 4 ), [Eu III or Tb III (H 3 L 2-Me )(OAc)](ClO 4 ) 2 ·2EtOH ( 2 , 5 ), and [Eu III or Tb III (H 3 L 5-Me )(OAc)](ClO 4 ) 2 ·MeOH ( 3 , 6 ), were studied, where H 3 L 2-Me = tris[2-(((2-methylimidazol-4-yl)methylidene)amino)ethyl]amine and H 3 L 5-Me = tris[2-(((5-methylimidazol-4-yl)methylidene)amino)ethyl]amine, and OAc = acetate ion. Each Eu III or Tb III ion is coordinated by a heptadentate tripodal and a bidentate acetate ligand, resulting in Δ- and Λ-enantiomorphs because of the screw coordination arrangement of the tripodal ligand. Intermolecular imidazole⋯acetate hydrogen bonding gives rise to three types of enantioselective assemblies. Compounds 1 and 4 form homochiral 1D chains comprising an undulating double layer that crystallizes into a conglomerate, whereas 2 and 5 form homochiral, single-layer, 1D chains, and crystallize into a racemic crystal. 3 and 6 form heterochiral dimers possessing an inversion center. The solid-state emission spectra of the complexes display sharp bands corresponding to the f–f transitions. Quantum yields ( Ф ) of 0.21, 0.24, and 0.24 and lifetimes ( τ ) of 1.03, 0.98, and 0.97 ms were obtained for the Eu III complexes 1 , 2 , and 3 , respectively, under 310 nm excitation. The corresponding values for the Tb III complexes 4 , 5 , and 6 were Ф = 0.088, 0.10, and 0.043 and τ = 0.46, 0.48, and 0.50 ms, respectively.

Three iron(II) complexes with a linear symmetrical pentadentate ligand H 2 L 1 and a monodentate ligand X (X = N 3 − , NCS − , NCSe − ), [Fe II N 3 (H 2 L 1 )]BPh 4 ( 1 ), [Fe II NCS(H 2 L 1 )]BPh 4 ( 2 ), and [Fe II NCSe(H 2 L 1 )]BPh 4 ( 3 ), were synthesized and characterized, where H 2 L 1 denotes bis( N , N ′-2-methylimidazol-4-yl-methylideneaminopropyl)methylamine. Compounds 1 , 2 and 3 consist of a mononuclear complex-cation of [Fe II X(H 2 L 1 )] + (X = N 3 − , NCS − , NCSe − ) and a tetraphylborate (BPh 4 − ) anion. Each complex-cation has an octahedral coordination geometry with N 6 donor atoms of a linear pentadentate ligand of H 2 L 1 and a nitrogen atom of N 3 − , NCS − , or NCSe − , in which the linear pentadentate ligand is folded to coordinate to Fe II ion in a cis -form. One of two imidazole groups of a complex-cation is hydrogen bonded to N 3 − , NCS − , or NCSe − of the adjacent complex-cation to form a cyclic dimer structure for 1 and a zigzag-chain structure for 2 and 3 . The temperature dependence of the magnetic data revealed that 1 , 2 and 3 are high-spin (HS) complexes.

Two racemic tridentate ligands, N-[(imidazol-4-yl)methylidene]- dl -alanine (H2L dl -ala) and N-[(imidazol-4-yl)methylidene]- dl -phenylalanine (H2L dl -phe), were synthesized by the 1:1 condensation reaction of 4-formylimidazole and either of dl -alanine and dl -phenylalanine, respectively. The EuIII complexes ‘fac’-[EuIII(HL dl -ala)3]·8H2O (1) and ‘mer’-[EuIII(HL dl -phe)3]·7.75H2O (2) were synthesized by mixing the ligand and EuIII(acetate)3 n-hydrate with 3:1 M ratio in methanol and the crystal structures were determined. Compounds 1 and 2 with three tridentate ligands have ‘facial’ and ‘meridional’ geometries, respectively, while they have a tricapped trigonal prismatic (TTP) and a capped square antiprismatic (CSAP) coordination geometry, respectively. In the crystal lattice, 1 consists of enantiomers ‘fac’-[EuIII(HL d -ala)3] and ‘fac’-[EuIII(HL l -ala)3], while 2 consists of ‘mer’-[EuIII(HL d -phe)2(HL l -phe)] and ‘mer’-[EuIII(HL d -phe)(HL l -phe)2]. Compounds 1 and 2 displayed sharp emission bands based on the f−f transitions by excitation and showed a different emission pattern due to their ‘fac’- and ‘mer’-coordination geometries. The luminescence quantum yields and life times of 1 and 2 were estimated to be (Φ = 0.25 and 1.40 ms) and (Φ = 0.30 and 1.23 ms), respectively.

Atmospheric CO2 fixation by a basic reaction mixture of [NiII(3-MeOsaltn)(H2O)2] and GdIII(NO3)3·6H2O gave a carbonate-bridged tetranuclear NiII2GdIII2 complex, (μ4-CO3)2[NiII(3-MeOsaltn)(MeOH)GdIII(NO3)]2·H2O, where 3-MeOsaltn denotes N,N′-bis(3‐methoxy-2-oxybenzylidene)-1,3-propanediaminato. The tetranuclear structure possessing an inversion center can be described as two [NiIIGdIII] binuclear units bridged by two carbonate CO32 − ions: two oxygen atoms of the carbonate ion bridge the high-spin NiII and GdIII ions of a binuclear unit and the remaining oxygen atom of the carbonate ion coordinates to a GdIII ion of the adjacent binuclear unit. The temperature-dependent magnetic susceptibilities, from 1.9 to 300 K, follow the Curie–Weiss equation of χMT = C / (T − θ) with θ = + 2.3 K and C = 18.24 cm3 K mol− 1, suggesting a ferromagnetic interaction. The magnetic data were well reproduced assuming two independent [NiII–GdIII] binuclear units with the parameters of J(Ni–Gd) = + 1.2 cm− 1 and D = + 2.1 cm− 1.

Two new iron(II) complexes, [FeII(HLMe)2](ClO4)2 (1) and its ethanol adduct [FeII(HLMe)2](ClO4)2·EtOH (2) were synthesized by selective crystallization in methanol and ethanol, respectively, where HLMe is a tridentate N3 ligand, 2-methylimidazol-4-yl-methylideneamino-2-ethylpyridine, and their structures and magnetic properties were investigated. Each compound contains the same octahedrally N6 coordinated complex-cation [FeII(HLMe)2]2+ and two ClO4− ions. The non-solvated compound 1 is the HS (S = 2) complex without spin transition over the 5–300 K temperature range, and has the homochiral 1D helical-chain structure constructed of the intermolecular NH···O− hydrogen bonds between ClO4− ions and neighboring imidazole NH groups of the [FeII(HLMe)2]2+ cations. The ethanol adduct 2 shows a gradual one-step spin transition between the HS (S = 2) and LS (S = 0) states, and has two crystallographically independent iron(II) sites with two NH(imidazole)···OH(EtOH)···O(ClO4−) hydrogen bonds of Fe(1) site and two NH(imidazole)···O(ClO4−) hydrogen bonds of Fe(2) site. There are no further intermolecular interactions to produce an extended structure in a crystal lattice of 2. The presence or absence of thermal spin transition is related to the structural distortion of each HS molecule of these perchlorate salts associated with their surroundings of intermolecular hydrogen bonds.

We found for the first time that Zygomycetes species showed resistance to Aureobasidin A, an antifungal agent. A novel family of neutral glycosphingolipids (GSLs) was found in these fungi and isolated from Mucor hiemalis, which is a typical Zygomycetes species. Their structures were completely determined by compositional sugar, fatty acid, and sphingoid analyses, methylation analysis, matrix-assisted laser desorption ionization time-of-flight/mass spectrometry, and (1)H NMR spectroscopy. They were as follows: Gal beta 1-6Gal beta 1-1Cer (CDS), Gal alpha 1-6Gal beta 1-6Gal beta 1-1Cer (CTS), Gal alpha 1-6Gal alpha 1-6Gal beta 1-6Gal beta 1-1Cer (CTeS), and Gal alpha 1-6Gal alpha 1-6Gal alpha 1-6Gal beta 1-6Gal beta 1-1Cer (CPS). The ceramide moieties of these GSLs consist of 24:0, 25:0, and 26:0 2-hydroxy acids as major fatty acids and 4-hydroxyoctadecasphinganine (phytosphingosine) as the sole sphingoid. However, the glycosylinositolphosphoceramide families that are the major GSLs components in fungi were not detected in Zygomycetes at all. This seems to be the reason that Aureobasidin A is not effective for Zygomycetes as an antifungal agent. Our results indicate that the biosynthetic pathway for GSLs in Zygomycetes is significantly different from those in other fungi and suggest that any inhibitor of this pathway may be effective for mucormycosis, which is a serious pathogenic disease for humans.

Background Improvement of transduction and augmentation of cytotoxicity are crucial for adenoviruses (Ad)-mediated gene therapy for cancer. Down-regulated expression of type 5 Ad (Ad5) receptors on human tumors hampered Ad-mediated transduction. Furthermore, a role of the p53 pathways in cytotoxicity mediated by replication-competent Ad remained uncharacterized. Methods We constructed replication-competent Ad5 of which the E1 region genes were activated by a transcriptional regulatory region of the midkine or the survivin gene, which is expressed preferentially in human tumors. We also prepared replication-competent Ad5 which were regulated by the same region but had a fiber-knob region derived from serotype 35 (AdF35). We examined the cytotoxicity of these Ad and a possible combinatory use of the replication-competent AdF35 and Ad5 expressing the wild-type p53 gene (Ad5/p53) in esophageal carcinoma cells. Expression levels of molecules involved in cell death, anti-tumor effects in vivo and production of viral progenies were also investigated. Results Replication-competent AdF35 in general achieved greater cytotoxic effects to esophageal carcinoma cells than the corresponding replication-competent Ad5. Infection with the AdF35 induced cleavages of caspases and increased sub-G1 fractions, but did not activate the autophagy pathway. Transduction with Ad5/p53 in combination with the replication-competent AdF35 further enhanced the cytotoxicity in a synergistic manner. We also demonstrated the combinatory effects in an animal model. Transduction with Ad5/p53 however suppressed production of replication-competent AdF35 progenies, but the combination augmented Ad5/p53-mediated p53 expression levels and the downstream pathways. Conclusions Combination of replication-competent AdF35 and Ad5/p53 achieved synergistic cytotoxicity due to enhanced p53-mediated apoptotic pathways. Electronic supplementary material The online version of this article (doi:10.1186/s12885-015-1482-8) contains supplementary material, which is available to authorized users.

The majority of malignant mesothelioma possesses the wild-type p53 gene with a homologous deletion of the INK4A/ARF locus containing the p14(ARF) and the p16(INK4A) genes. We examined whether forced expression of p53 inhibited growth of mesothelioma cells and produced anti-tumor effects by a combination of cisplatin (CDDP) or pemetrexed (PEM), the first-line drugs for mesothelioma treatments. Transduction of mesothelioma cells with adenoviruses bearing the p53 gene (Ad-p53) induced phosphorylation of p53, upregulated Mdm2 and p21 expression levels and decreased phosphorylation of pRb. The transduction generated cleavage of caspase-8 and -3, but not caspase-9. Cell cycle analysis showed increased G0/G1- or G2/M-phase populations and subsequently sub-G1 fractions, depending on cell types and Ad-p53 doses. Transduction with Ad-p53 suppressed viability of mesothelioma cells and augmented the growth inhibition by CDDP or PEM mostly in a synergistic manner. Intrapleural injection of Ad-p53 and systemic administration of CDDP produced anti-tumor effects in an orthotopic animal model. These data collectively suggest that Ad-p53 is a possible agent for mesothelioma in combination with the first-line chemotherapeutics.

We found for the first time that Zygomycetes species showed resistance to Aureobasidin A, an antifungal agent. A novel family of neutral glycosphingolipids (GSLs) was found in these fungi and isolated from Mucor hiemalis, which is a typical Zygomycetes species. Their structures were completely determined by compositional sugar, fatty acid, and sphingoid analyses, methylation analysis, matrix-assisted laser desorption ionization time-of-flight/mass spectrometry, and (1)H NMR spectroscopy. They were as follows: Gal beta 1-6Gal beta 1-1Cer (CDS), Gal alpha 1-6Gal beta 1-6Gal beta 1-1Cer (CTS), Gal alpha 1-6Gal alpha 1-6Gal beta 1-6Gal beta 1-1Cer (CTeS), and Gal alpha 1-6Gal alpha 1-6Gal alpha 1-6Gal beta 1-6Gal beta 1-1Cer (CPS). The ceramide moieties of these GSLs consist of 24:0, 25:0, and 26:0 2-hydroxy acids as major fatty acids and 4-hydroxyoctadecasphinganine (phytosphingosine) as the sole sphingoid. However, the glycosylinositolphosphoceramide families that are the major GSLs components in fungi were not detected in Zygomycetes at all. This seems to be the reason that Aureobasidin A is not effective for Zygomycetes as an antifungal agent. Our results indicate that the biosynthetic pathway for GSLs in Zygomycetes is significantly different from those in other fungi and suggest that any inhibitor of this pathway may be effective for mucormycosis, which is a serious pathogenic disease for humans.

The efficient processing of human immunodeficiency virus type 1 Gag–Pol requires not only protease activity but also specific reverse transcriptase (RT) and integrase sequences. However, the critical amino acid residues of the HIV-1 Pol gene involved in protease-mediated Gag–Pol processing have not been precisely defined. Here, we found that the substitution of Thr-128 or Tyr-146 with Ala markedly impaired the proteolytic processing of the MA/CA, p66/p51 and RT/IN sites but did not affect the normal processing of other sites. Moreover, a Thr-128 or Tyr-146 mutation in RT abolished RT dimerization in vitro. These results suggest that Thr-128 and Tyr-146 within the RT region play important roles in protease-mediated Gag–Pol processing.Structured summary of protein interactionsRT and RT physically interact by cross-linking study (View interaction: 1, 2, 3).CK2 alpha phosphorylates RT by protein kinase assay (View interaction).