(31E,32Z,71E,72Z)-4,8-Bis(3,5-di-chloro-phen-yl)-14,33,53,73-tetra-propyl-11H,32H,51H,72H-1,5(2,5),3,7(5,2)-tetra-pyrrola-2,6(2,5)-di-thiophena-cyclo-octa-phane.

Purple crystals of the title compound, C50H44Cl4N4S2 were obtained from the reaction of 2,5-bis-(4-propyl-1H-pyrrol-2-yl)thio-phene and 3,5-di-chloro-benzaldehyde in the presence of tri-fluoro-acetic acid for 3 h and subsequent addition of p-chloranil. The macrocycle in the title compound can be described as a highly planar structure wthe the average deviation of the 32 macrocyclic atoms from the least-squares plane being 0.0416 Å. Its mol-ecular conformation is stabilized by two intra-molecular N-H⋯N bonds and a three-dimensional network is formed by C-H⋯π inter-actions.

Preparation of a Water-Soluble Glycopolymer Bearing Porphyrin Skeletons and Its Biological Properties.

A known tetraphenyl porphyrin (TPP) having an amino functional group [5-(4-aminophenyl)-10,15,20-(triphenyl)porphyrin] was converted into the corresponding monomer by means of condensation with acryloyl chloride. Simple radical polymerization of the porphyrin monomer and a glycosyl monomer in the presence of acrylamide as a regulator monomer in order to avoid steric interference gave a water-soluble glycopolymer bearing porphyrin moieties. Spectroscopic analyses suggested incorporation of porphyrin moieties in the glycopolymer. The physical properties of the water-soluble glycopolymer bearing porphyrin moieties were examined in aqueous media, and the results also indicated the incorporation of TPP moieties in the polymer. Uptake of the polymer into HeLa cells was observed, and the cytotoxicity of the polymer was confirmed by microscopic analyses. The glycopolymer bearing porphyrin moieties is promising not only for photodynamic therapy but also as an anti-cancer reagent.

A case of Rasmussen's aneurysm caused by pulmonary nontuberculous mycobacterium.

Rasmussen's aneurysm was originally described as a rare cause of hemoptysis in tuberculosis. Dilatation of the pulmonary artery wall is caused by tuberculosis inflammation. Recently, the incidence of non-tuberculous mycobacterial (NTM) disease has increased; it now exceeds that of tuberculosis. We report a Rasmussen's aneurysm due to NTM.

Syn and Anti Metal Complexes of 24π Antiaromatic Bis(Dicarbonylrhodium(I))Dithiaamethyrin.

From the reaction of sterically less hindered tetrapropyl[24]dithiaamethyrin(1.0.0.1.0.0) 5, with [Rh(CO)2 Cl]2 , a unique anti form of the bis(dicarbonylrhodium(I)) complex (6-anti), where two rhodium ions are on the opposite faces of the macrocyclic ligand, was isolated for the first time in 12% yield along with the corresponding syn isomer (6-syn, 61% yield). These structures were characterized in detail by single-crystal X-ray structure analysis. Compound 6-syn exhibited a bowl-shaped structure with the two rhodium atoms separated by a distance of ∼4.5 Å. In contrast, 6-anti contained a wave-shaped macrocycle with a distance of ∼5.3 Šbetween the two rhodium atoms. Furthermore, the 1 H nuclear magnetic resonance spectra and density functional theory calculation results revealed that 6-anti had a stronger paratropic ring current and a more planar structure than 6-syn. The isolation of both 6-anti and 6-syn enabled detailed discussion of the structure-property relationship.

Validation of Newly Proposed Time to Transarterial Chemoembolization Progression in Intermediate-Stage Hepatocellular Carcinoma Cases.

BACKGROUND/AIM: Determination of failure of transarterial chemoembolization (TACE) for treatment of Barcelona Clinic Liver Cancer stage B (BCLC-B) hepatocellular carcinoma (HCC) has become important because of the development of tyrosine kinase inhibitor (TKI) treatment. We evaluated the usefulness and efficacy of the newly proposed time to TACE progression (TTTP). PATIENTS AND METHODS: From 2006 to 2016, 192 BCLC-B HCC patients [median age 72 years, male/female ratio = 149/43, Child-Pugh score 5/6/7 = 106/56/30, albumin-bilirubin (ALBI) grade 1/2 = 64/128, Kinki criteria B1/B2 = 64/128] were enrolled. TTTP was defined based on a previous report and first imaging performed 3 months after initial TACE had been used to obtain baseline images. The patients were divided into three groups according to TTTP (<5, 5-10, and ≥10 months; group I, II, and III, respectively). We evaluated the relationship between TTTP and overall survival (OS) as well as the prognostic factors for death. RESULTS: The median number of TACE procedures was 4 (interquartile range 3-7). There was a moderate correlation between TTTP and OS (r = 0.527, 95% CI 0.416-0.622, p < 0.001). The median survival for group I (n = 78), II (n = 49), and III (n = 65) was 24.6, 34.7, and 49.5 months, respectively (group I vs. group II, p = 0.023; group I vs. group III, p < 0.001; group II vs. group III, p = 0.037; Holm's method). ALBI grade 2 (HR 1.548, 95% CI 1.004-2.388, p = 0.048), alpha-fetoprotein (>100 ng/mL) (HR 1.540, 95% CI 1.035-2.291, p = 0.033), and TTTP (<5 months) (HR 2.157, 95% CI 1.447-3.215, p < 0.001) were significant prognostic factors for death in multivariate Cox hazard analysis. CONCLUSION: In patients with reduced TTTP, especially <5 months, it might be difficult to improve prognosis with a repeated TACE procedures. In such cases, reconsideration of the therapeutic strategy might be needed when possible.

Tumor Markers AFP, AFP-L3, and DCP in Hepatocellular Carcinoma Refractory to Transcatheter Arterial Chemoembolization.

BACKGROUND/AIM: We examined tumor marker levels to assess in more detail transcatheter arterial chemoembolization (TACE)-refractory hepatocellular carcinoma (HCC). MATERIALS AND METHODS: We enrolled patients treated from 2000 to 2011 for HCC beyond the Milan criteria who had good hepatic reserve function (Child-Pugh A) and no portal vein thrombosis or metastases (n = 154). The modified criteria for being TACE-refractory according to the Liver Cancer Study Group of Japan (m-LCSGJ), from which the tumor marker item was excluded, and the Assessment for Retreatment with TACE (ART) score were used for determining whether the HCC was TACE refractory. α-Fetoprotein ≥ 100 ng/ml, fucosylated α-fetoprotein ≥ 10%, and des-gamma-carboxy prothrombin ≥ 100 mAU/ml were used to define whether tumor markers were positive. We added up the number of positive tumor markers as a prognostic score to assess in more detail the evaluation of TACE-refractory HCC. RESULTS: In order to divide the patients into a refractory and nonrefractory group, the m-LCSGJ criteria [mean survival time (MST) 27.1 vs. 49.9 months; p < 0.001] were superior to the ART score (MST 22.0 vs. 35.1 months; p = 0.051). In the refractory group according to the m-LCSGJ criteria, the patients with a low score of positive tumor markers (<2) after 2 sessions of TACE (n = 36) showed a better prognosis than the others (n = 72) (MST 37.7 vs. 23.2 months; p = 0.014). CONCLUSION: Patients being nonrefractory according to the m-LCSGJ criteria had a better response, and using the number of tumor markers (≥ 2) is an easy method for predicting the response to TACE and for a more detailed evaluation of TACE-refractory HCC.

Prognosis and therapy for ruptured hepatocellular carcinoma: problems with staging and treatment strategy.

BACKGROUND: There are no clear criteria established for treating a ruptured hepatocellular carcinoma (HCC). To elucidate the clinical features of affected patients, we examined prognosis and therapy choices. MATERIALS/METHODS: We enrolled 67 patients treated for a ruptured HCC (HCV 44, HBV 5, HBV+HCV 1, alcohol 2, others 15; naïve HCC 34, recurrent 33) from 2000 to 2013, and investigated their clinical background and prognosis. RESULTS: Median survival time (MST) for all cases was 4 months. For patients who survived for more than 1 year after rupture, the percentages of Child-Pugh C and positive for portal vein tumor thrombosis (PVTT)/extrahepatic metastasis were less than for those who died within 1 year. Child-Pugh classification (A:B:C=14:15:5 vs. 4:9:20, P<0.001) was better, while the percentage of patients with multiple tumors was lower [19/34 (55.9%) vs. 29/33 (87.9%), respectively; P<0.001] in the naïve group. The 1- and 3-year survival rates were better in the naïve as compared to the recurrent group (60.6% and 33.3% vs. 12.6% and 0%, respectively; P<0.01). MST according to modified TNM stage (UICC 7th) calculated after exclusion of T4 factor of rupture, stage I was better than others (22.7 vs. (II) 2.2, (III) 1.2, and (IV) 0.7 months) (P=0.010). CONCLUSION: In patients with a ruptured HCC, especially those with a single tumor, and without decompensated liver cirrhosis and PVTT/extrahepatic metastasis, better prognosis can be expected with curative treatment. The present naïve group included more of such cases than the recurrent group, indicating the effectiveness of curative therapy.

Synthesis and antiaromatic properties of highly planar dithiaamethyrin.

2,5-Bis(4-propyl-2-pyrrolyl)thiophene was reacted with aryl aldehydes to afford large porphyrinoids; [24]dithiaamethyrin(1.0.0.1.0.0) and [36]trithianonaphyrin(1.0.0.1.0.0.1.0.0). X-ray crystallography of the dithiaamethyrin revealed a highly planar ring structure with mean plane deviation (MPD) value of 0.053 Å. A large positive NICS(0) value (+13.9 ppm) calculated for this planar 24π system unambiguously indicates an antiaromatic character that is consistent with a remarkably low field (1) H chemical shift of the inner NH proton at 24.0 ppm. The magnitude of the paratropic ring current effect in the 24π amethyrin framework in the free base form and the diprotonated form was discussed on the basis of the MPD value and the NICS value. The present dithiaamethyrin is much more strongly antiaromatic than the dodecaalkylamethyrin in their free base forms, but the order inversed in their diprotonated forms.

Preparation of polypseudorotaxanes composed of cyclodextrin and polymers in microspheres.

We prepared polypseudorotaxanes (PPRXs) composed of cyclodextrin (CyD) and polyethylene glycol (PEG) inside microspheres (MSs) by an emulsifying process using polypropylene glycol (PPG) that shows temperature-dependent hydrophilicity changes; PPG is hydrophobic at high temperatures but hydrophilic at low temperatures. An aqueous solution of CyD and PEG was dispersed as droplets in PPG at 60°C then cooled to 0°C to allow water of droplets to transfer into PPG. On removal of water in the droplets, CyD and PEG were left behind as a CyD/PEG PPRX inside the solid-state MSs. Examination of α-, ß-, and γ-CyD revealed that α-CyD was suitable for the formation of PPRX containing PEG in this MS preparation procedure. Interestingly, a new PPRX composed of α-CyD and PPG was formed in the α-CyD MSs when they were prepared in the absence of PEG from the aqueous solution of α-CyD. This MS fabrication procedure can control the size and shape of PPRX particles, and will contribute to the production of new types of CyD inclusion complexes.

18F-FDG-PET/CT predicts the distribution of microsatellite lesions in hepatocellular carcinoma.

This study was conducted to investigate whether fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is useful for predicting the distance of intrahepatic metastases and microvascular invasion from the main tumor and the pattern of postoperative recurrence. A total of 89 consecutive patients who underwent 18F-FDG PET/CT prior to liver resection for hepatocellular carcinoma (HCC) between April, 2006 and December, 2011 were enrolled in this study. The distance between the microsatellite lesion and the main nodule (microsatellite distance) was analyzed and measured pathologically. The correlation between maximal standardized uptake values (SUVmax) and microsatellite distance was analyzed and the independent risk factors for microsatellite distance >1 cm were assessed. The postoperative recurrence patterns were divided into no recurrence, intrahepatic recurrence and extrahepatic recurrence. SUVmax and the distribution of microsatellite lesions were compared among these groups. The postoperative recurrence patterns were also analyzed according to the SUVmax and the microsatellite lesion pattern. SUVmax was found to be significantly correlated with the distance from the microsatellite lesion to the main nodule (r=0.57, P<0.0001). On the multivariate analysis of microsatellite distance >1 cm, the only significant factor was SUVmax [P=0.002; hazard ratio=1.60; 95% confidence interval (CI): 1.23-2.26]. The optimal cutoff value of SUVmax for microsatellite distance >1 cm was 8.8. The mean SUVmax and the microsatellite distance were highest in patients with postoperative extrahepatic metastases (8.6 and 9,160 µm, respectively). In conclusion, the SUVmax of 18F-FDG PET/CT reflects microsatellite distance and the patterns of postoperative recurrence in HCC. Therefore, 18F-FDG PET/CT may be a useful imaging modality for determining the resection margin and the treatment protocol for HCC.

Simple preparation of green fluorescent protein conjugated with ß-cyclodextrin in a site specific manner.

We have site-directedly linked a green fluorescent protein (GFP) variant and a ß-cyclodextrin (ß-CD) with a simple method to develop a basic complex for sophisticated supramolecules. We have confirmed ß-CD grafting on GFP with several methods including matrix-assisted laser desorption/ionization linear time-of-flight mass spectrometry (MALDI-TOF MS) without protease digestion and characterized the complex as well. In consideration of the resulting properties, the product we plainly and efficiently obtained could have applications related to sensing devices and drug delivery systems.

Importance of screening for synchronous malignant neoplasms in patients with hepatocellular carcinoma: impact of FDG PET/CT.

BACKGROUND & AIM: Synchronous neoplasms (SNs) are occasionally found in hepatocellular carcinoma (HCC). We examined such cases and the efficacy of 18-fluoro-2-deoxyglucose positron-emission tomography computed tomography (PET/CT), retrospectively. MATERIALS AND METHODS: We investigated 687 naïve HCC, who were admitted to our hospitals, encountered from October 2006 to December 2010 and evaluated the clinical backgrounds. All study protocols, was approved by our Institutional Ethics Committee. The usefulness of detecting SNs by PET/CT was evaluated in 234 patients who underwent PET/CT (PET group) and in 453 (non-PET group) examined in the same period. We noted the presence of SNs, defined as primary extrahepatic malignant neoplasms within 1 year of diagnosis of HCC. RESULTS: SNs were observed in 48 of 687 patients (54 tumours, 7.0%). SNs were detected by PET/CT in 18, which was 7.7% of PET group. The detection rate for SNs, were increased to 11.1% (26/234) in PET group by using together with upper gastrointestinal endoscopy and routine enhanced CT for HCC, which was greater than that of non-PET group (22/453, 4.9%) (P < 0.001). CONCLUSION: SNs were pointed out more frequently in PET group than non-PET group (11.1% vs. 4.9%). FDG PET/CT can enhance the detection ability for SNs in naïve HCC.

Advantageous grain boundaries in iron pnictide superconductors.

High critical temperature superconductors have zero power consumption and could be used to produce ideal electric power lines. The principal obstacle in fabricating superconducting wires and tapes is grain boundaries-the misalignment of crystalline orientations at grain boundaries, which is unavoidable for polycrystals, largely deteriorates critical current density. Here we report that high critical temperature iron pnictide superconductors have advantages over cuprates with respect to these grain boundary issues. The transport properties through well-defined bicrystal grain boundary junctions with various misorientation angles (θ(GB)) were systematically investigated for cobalt-doped BaFe(2)As(2) (BaFe(2)As(2):Co) epitaxial films fabricated on bicrystal substrates. The critical current density through bicrystal grain boundary (J(c)(BGB)) remained high (>1 MA cm(-2)) and nearly constant up to a critical angle θ(c) of ∼9°, which is substantially larger than the θ(c) of ∼5° for YBa(2)Cu(3)O(7-δ). Even at θ(GB)>θ(c), the decay of J(c)(BGB) was much slower than that of YBa(2)Cu(3)O(7-δ).

Radiofrequency ablation therapy for hepatocellular carcinoma in elderly patients.

BACKGROUND AND AIM: With the aging of society, the number of elderly patients with hepatocellular carcinoma (HCC) has been increasing in Japan. The Government of Japan defines elderly as being over 65 and has divided the elderly into two stages: the first elderly stage (< 75 years old) and the second elderly stage (> or = 75). We investigated the efficacy and safety of radiofrequency ablation therapy (RFA) in patients in the second elderly stage in comparison with other HCC patients, retrospectively. METHODS: Two hundred six patients with HCC, who were within the Milan criteria, with low-grade performance status (0 or 1) and a Child-Pugh classification of A or B were enrolled. All were treated with RFA from January 2000 to December 2008 as an initial therapy and were divided into elderly HCC group (e-HCC group; > or = 75, n = 63) and non e-HCC group (< 75, n = 143), and their clinical data and survival rates were compared. RESULTS: Age and the level of protein induced by vitamin K absence or antagonist (PIVKA-II) were higher in the e-HCC group as compared with the non e-HCC group (78.3 +/- 3.2 vs 64.2 +/- 7.5 years, 676.3 +/- 2643.7 vs 142.4 +/- 442.2 mAU/mL: P < 0.01, respectively). There were no significant differences for Child-Pugh class, tumor node metastasis stage, and Japan Integrated Stage score and in survival rates after 3, and 5 years between the groups (e-HCC group: 82.5% and 49.7%, respectively; non e-HCC group: 78.3% and 57.5%, respectively). There were no severe complications in the e-HCC group. CONCLUSIONS: Elderly HCC patients, who have good performance status, should be treated in the same manner and with the same strategy as young HCC patients.

Risk factors for death in 224 cases of hepatocellular carcinoma after transcatheter arterial chemoembolization.

BACKGROUND/AIMS: Transcatheter arterial chemoembolization (TACE) has been reported as effective therapy for unresectable hepatocellular carcinoma (HCC), however, few have described methods for predicting prognosis, especially in patients treated by repeated TACE. To determine risk factors for death and try to predict the prognosis, we evaluated clinical data. METHODOLOGY: We retrospectively analyzed the clinical parameters of 224 patients with unresectable HCC treated with repeated TACE from January 1997 to December 2007. TACE was repeated when recurrence was diagnosed by tumor marker elevation and/or dynamic computed tomography findings. Factors affecting survival were evaluated using multivariate analysis after univariate analysis. Next, we combined the score for each significant factor into a single prognostic score and added up the positive factors in each case, then analyzed the significance of prognosis, after which the results were compared with other prognostic scoring systems. RESULTS: Multivariate analysis revealed that bilobular HCC, alpha-fetoprotein (> or = 400 ng/ml), tumor invasion of the portal vein, tumor size (> or = 10 cm), and albumin (< 2.8 g/dl) were related to poor prognosis, and developed a prognostic scoring system from those. According to that score, patients were classified into 5 groups. CONCLUSION: Our scoring system was easily performed and the results showed that repeated TACE should not be administered to patients with scores of 3 or more.

Primary hepatic marginal zone B cell lymphoma of mucosa-associated lymphoid tissue type: case report and review of the literature.

A primary hepatic marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT) is very rare. We found a solitary mass 27 mm in size in the left lobe of the liver of a 58-year-old Japanese man with a history of hepatitis-C infection. Based on the results of imaging studies, the tumor was diagnosed as a hepatocellular carcinoma (HCC). The left lobe of the liver was lobectomized and microscopic findings showed that the tumor was a hepatic MALT lymphoma, while immunohistochemistry showed it to be positive for CD20 and CD79a. In a fluorodeoxyglucose-positron emission tomography examination integrated with computed tomography scanning (FDG-PET CT) before surgery, the tumor was revealed to have a high standardized uptake value (SUV) for FDG. The patient received chemotherapy after surgery. To the best of our knowledge, 45 cases had been reported with a mean age for all patients of 61.4 years. The pathogenesis remains unclear, although half of the patients had a past history of chronic inflammatory liver disease. Surgical resection was performed in most cases and some patients received postoperative chemotherapy or radiotherapy. The clinicopathologic characteristics and management of this extremely rare disease are also discussed.

Efficacy of radiofrequency ablation therapy compared to surgical resection in 164 patients in Japan with single hepatocellular carcinoma smaller than 3 cm, along with report of complications.

BACKGROUND/AIMS: Radiofrequency ablation therapy (RFA) has become widely used against hepatocellular carcinoma (HCC), mainly because of its ease of use, lower level of invasiveness, and high level of effectiveness. To compare the efficacy and safety of RFA with surgery, we retrospectively investigated relevant patient clinical data. METHODOLOGY: The patients with a single HCC (3 cm > or =, Child-Pugh A or B) who were treated with RFA (RFA-group: n=105) or surgery (Surgery-group: n=59) from January 2000 to June 2007 were enrolled. RESULTS: The ratio of patients classified as Child-Pugh B was greater in RFA-group (24.8% vs. 8.5%, P=0.011), though the sizes of the tumors were not significantly different. There were no significant differences for survival rates or disease free survival rates after 3- and 5-years (RFA-group vs. Surgery-group; survival: 87.8 and 59.3% vs. 91.4 and 59.4%, disease free survival: 58.7 and 24.6% vs. 64.3 and 22.4%, respectively). As for complications, in RFA-group there was no severe complication while there was 1 case of postoperative hepatic failure death and 2 with a postoperative abscess in Surgery-group. CONCLUSIONS: In the present study, patients with a single HCC smaller than 3cm who underwent RFA had a lower frequency of severe complications, thus the efficacy of RFA was thought to be equal to a surgical procedure.

Determination of the capped site sequence of mRNA based on the detection of cap-dependent nucleotide addition using an anchor ligation method.

The sequence analysis of the 5' ends of cDNAs prepared using the anchor ligation method has revealed that most of the full-length cDNAs have an additional dGMP at their 5' end that is absent in the corresponding genome sequence. Using model RNA transcripts with cap analogues possessing 7-methylguanosine and adenosine, the base of the added nucleotide has been shown to be complementary to the base of the cap analogue, suggesting that the cDNAs possessing an additional dGMP are derived from intact mRNAs with the cap structure. On the other hand, cap-free RNA did not produce cDNA with an extra dGMP. These findings suggest that we can determine whether or not the cDNA starts from the capped site sequence of mRNA based on the presence or absence of an additional dGMP at the 5' end of the cDNA synthesized using the anchor ligation method. This approach will be useful to determine the capped site sequence of mRNA, thus, to identify transcription start sites.

Synthesis of Vinylene-Co,N-Linked Multi(porphyrin)s by the Addition of Free-Base Porphyrins to a C(2)H(2) Complex of Cobalt(III) Porphyrin and Their Oxidative Rearrangement to Vinylene-N,N'-Linked Multi(porphyrin)s.

The nucleophilic addition reaction of a pyrrole nitrogen of free-base porphyrins to a pi-complexed acetylene ligand in a cationic Co(III) porphyrin intermediate afforded good yields of vinylene-Co,N'-linked bis(porphyrin)s, (Por)Co(III)-CH=CH-(N-Por)H(2). N-substituted porphyrin free bases are N-vinylated regioselectively at the pyrrole adjacent to the original N-substituted pyrrole in this reaction. Tris- and tetrakis(porphyrin)s have been prepared by reacting a vinylene-N,N'-linked bis(meso-tetraarylporphyrin) with (OEP)Co(III)(H(2)O)(2)ClO(4) (OEP: octaethylporphyrin dianion) and acetylene. The tetrakis(porphyrin) proved to be a 1:1 mixture of C(i)()- and C(2)-symmetric regioisomers. These organometallic Co(III) complexes underwent facile oxidative migration of the Co-bound vinyl group to a porphyrin pyrrole nitrogen when treated with Fe(III) salts or HClO(4) to provide moderate to good yields of Co(II) vinylene-N,N'-linked multi(porphyrin) complexes. (Vinylene-N,N')bis(porphyrin) free bases with combinations of different porphyrins have been obtained by this procedure. The homobinuclear (2Co(II), 2Cu(II), and 2Zn(II)) and heterobinuclear (Co(II)Cu(II) and Co(II)Zn(II)) complexes have been prepared and characterized spectroscopically. The single-crystal X-ray analysis of (CH=CH-N,N')[(OEP)Co(II)Cl][(TPP)Zn(II)Cl] (TPP: meso-tetraphenylporphyrin dianion) showed a face-to-face structure with an average inter-ring separation of 4.39 Å (triclinic P&onemacr;; Z = 2; a = 14.806(4), b = 18.703(10), c = 13.796(3) Å, alpha = 97.69(3), beta = 99.57(2), gamma = 96.74(3) degrees ).