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Introduction Three randomized controlled trials have resulted in extremely extensive application of the strategy of using neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) for patients with advanced epithelial ovarian cancer in Japan. This study aimed to evaluate the status and effectiveness of treatment strategies using NAC followed by IDS in Japanese clinical practice. Patients and methods We conducted a multi-institutional observational study of 940 women with Federation of Gynecology and Obstetrics (FIGO) stages III–IV epithelial ovarian cancer treated at one of nine centers between 2010 and 2015. Progression-free survival (PFS) and overall survival (OS) were compared between 486 propensity-score matched participants who underwent NAC followed by IDS and primary debulking surgery (PDS) followed by adjuvant chemotherapy. Results Patients with FIGO stage IIIC receiving NAC had a shorter OS (median OS: 48.1 vs. 68.2 months, hazard ratio [HR]: 1.34; 95% confidence interval [CI] 0.99–1.82, p = 0.06) but not PFS (median PFS: 19.7 vs. 19.4 months, HR: 1.02; 95% CI: 0.80–1.31, p = 0.88). However, patients with FIGO stage IV receiving NAC and PDS had comparable PFS (median PFS: 16.6 vs. 14.7 months, HR: 1.07 95% CI: 0.74–1.53, p = 0.73) and OS (median PFS: 45.2 vs. 35.7 months, HR: 0.98; 95% CI: 0.65–1.47, p = 0.93). Conclusions NAC followed by IDS did not improve survival. In patients with FIGO stage IIIC, NAC may be associated with a shorter OS.

PDF file - 84K, RT-PCR analysis of VASH2 and SVBP in human ovarian cancer cells and EL-4

PDF file - 32K, Proliferation and apoptosis of cancer cells in vivo

PDF file - 97K, RT-PCR analysis of VASH2 in murine tumorigenic cell lines

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PDF file - 39K, Possible splicing variants of human VASH2

We attempted to identify potent marker genes using a new statistical analysis and developed a prediction system for individual response to platinum/paclitaxel combination chemotherapy in ovarian cancer patients based on the hypothesis that expression analysis of a set of the key drug sensitivity genes for platinum and paclitaxel could allow us to predict therapeutic response to the combination. From 10 human ovarian cancer cell lines, genes correlative in the expression levels with cytotoxicities of cisplatin (CDDP) and paclitaxel were chosen. We first selected five reliable prediction markers for the two drugs from 22 genes already known as sensitivity determinants and then identified another 8 novel genes through a two-dimensional mixed normal model using oligomicroarray expression data. Using expression data of genes quantified by real-time reverse transcription-PCR, we fixed the best linear model, which converted the quantified expression data into an IC50 of each drug. Multiple regression analysis of the selected genes yielded three prediction formulae for in vitro activity of CDDP and paclitaxel. In the same way, using the same genes selected in vitro, we then attempted to develop prediction formulae for progression-free survival to the platinum/paclitaxel combination. We therefore constructed possible formulae using different sets of 13 selected marker genes (5 known and 8 novel genes): Utility confirmation analyses using another nine test samples seemed to show that the formulae using a set of 8 novel marker genes alone could accurately predict progression-free survival (r = 0.683; P = 0.042). [Mol Cancer Ther 2006;5(3):767–75]

Supplementary Data from Prediction of individual response to platinum/paclitaxel combination using novel marker genes in ovarian cancers

Background: In advanced or metastatic ovarian cancer patients, the therapeutic impact of molecular targeted agents and immunotherapy is limited, and current chemotherapeutic algorithm is still far from personalized medicine. We recently demonstrated that intraperitoneal carboplatin with dose-dense paclitaxel (ddTCip) therapy is a promising front-line chemotherapy even in the patients with residual peritoneal tumors, which led us to this theranostic study for biomarker discovery to realize the precision medicine (ID: UMIN000001713 on Feb 16 th , 2009). Methods: We first validated previously suggested markers (41 genes and 3 predictive models for the therapeutic efficacy and 31 polymorphisms for the toxicity), sought out more active effective biomarkers through genome-wide transcriptome and genotyping analyses, and then developed multiplex statistical prediction models for progression free-survival (PFS) and toxicity. Multiple regression analysis following forward stepwise method and Classification and Regression Trees (CART) algorithm were mainly employed to develop multiplex prediction models. Results: The association analyses with PFS in 76 patients followed by the validation study using data sets in 189 patients published in The Cancer Genome Atlas revealed that SPINK1 expression could be a possible predictive biomarker of ddTCip efficacy even when used alone, and multiple regression analyses provided a potent efficacy prediction model using expression data of 5 genes. SPINK1 appeared to be a critical resistant determinant of ddTCip therapy, which indicates the potential of SPINK1 also to be a novel therapeutic target. As for the toxicity prediction, ABCB1rs1045642 and ERCC1rs11615 polymorphisms appeared to closely associate with grade2-4 hematologic toxicity and peripheral neuropathy, respectively. We further successfully composed robust multiplex prediction models for the adverse events-CART models using a total of 4 genotype combinations and further powerful multiple regression models using 15 polymorphisms on 12 genes-. Conclusions: We newly proposed SPINK1 expression as a powerful predictive biomarker of the efficacy for ddTCip therapy and confirmed the predictive values of ABCB1 and/or ERCC1 polymorphisms for the toxicity. Multiplex prediction models composed herein were also found to work well for the prediction of therapeutic response. These may raise the potential to realize a precision medicine in the essential treatment for metastatic ovarian cancer patients.

Background: In advanced or metastatic ovarian cancer patients, the therapeutic impact of molecular targeted agents and immunotherapy is limited, and current chemotherapeutic algorithms are still far from personalized medicine. We recently demonstrated that intraperitoneal carboplatin with dose-dense paclitaxel (ddTCip) therapy is a promising front-line chemotherapy even in patients with residual peritoneal tumors, which led us to this theranostic study for biomarker discovery to realize precision medicine (ID: UMIN000001713 on Feb 16th, 2009). Methods: We first validated previously suggested markers (41 genes and 3 predictive models for therapeutic efficacy and 31 polymorphisms for toxicity), sought out more active effective biomarkers through genome-wide transcriptome and genotyping analyses, and then developed multiplex statistical prediction models for progression-free survival (PFS) and toxicity. Multiple regression analysis following the forward stepwise method and the classification and regression tree (CART) algorithm were mainly employed to develop multiplex prediction models. Results: The association analyses with PFS in 76 patients followed by the validation study using data sets in 189 patients published in The Cancer Genome Atlas revealed that SPINK1 expression could be a possible predictive biomarker of ddTCip efficacy even when used alone, and multiple regression analyses provided a potent efficacy prediction model using expression data of 5 genes. SPINK1 appeared to be a critical resistant determinant of ddTCip therapy, which indicates the potential of SPINK1 as a novel therapeutic target. For toxicity prediction, ABCB1 rs1045642 and ERCC1 rs11615 polymorphisms appeared to be closely associated with grade 2-4 hematologic toxicity and peripheral neuropathy, respectively. We further successfully composed robust multiplex prediction models for adverse events - CART models using a total of 4 genotype combinations and further powerful multiple regression models using 15 polymorphisms on 12 genes-. Conclusions: We newly proposed SPINK1 expression as a powerful predictive biomarker of the efficacy of ddTCip therapy and confirmed the predictive values of ABCB1 and/or ERCC1 polymorphisms for toxicity. The multiplex prediction models composed herein were also found to work well for the prediction of therapeutic response. These findings may raise the potential to realize precision medicine in the essential treatment for metastatic ovarian cancer patients.

Self-sampling human papillomavirus (HPV) testing has been introduced for cervical cancer screening worldwide. In Japan, there are two types (brush and sponge) of HPV self-sampling devices. However, the recommended type for cervical cancer screening remains unclear. This study aimed to evaluate the feasibility of the HPV self-sampling device-sponge type (HSD-ST). Additionally, we aimed to examine the positive rate (sensitivity) for cervical intraepithelial neoplasia (CIN) 2 or worse using the HSD-ST. Finally, we aimed to perform a questionnaire survey regarding the usability of the HSD-ST.We included 165 women who underwent HPV testing at one of three gynecologic clinics. First, the women used the HSD-ST and completed a questionnaire regarding its usability. Subsequently, they underwent physician-sampling HPV testing and cytology. We examined the agreement rate of HPV positivity between self- and physician-sampling HPV testing.The HPV-positive rates of self- and physician-collected samples were 59.4% and 62.4%, respectively, with an overall concordance rate of 88.5% and a calculated kappa coefficient of 0.76, indicating high concordance. Moreover, the positive (sensitivity) rates for CIN2 or worse were 81.4% and 89.8% in the self- and physician-collected samples, respectively.Our findings demonstrated the feasibility and usability of the HSD-ST.

Face-to-face noncovalent arene-fullerene interactions are important in several research fields such as synthetic chemistry, materials chemistry, and medicinal chemistry; however, their nature and strength are still poorly understood. In this study, we prepare a fullerene-based torsion balance containing thioanisole, phenol, naphthalene, azulene, and pyrene moieties as a unimolecular model system. Moreover, we compare the folding free energies between the folded and the unfolded conformers of a series of the molecular torsion balances to quantify noncovalent interactions between arenes and the fullerene surface. This work demonstrates that the contributions of polarizabilities, anionic charges, electronic dipole moments, and the number of arene rings to the interactions can be experimentally measured by analyzing the folding equilibrium of the molecular torsion balances.

In Japan, government support for human papillomavirus (HPV) vaccination began in November 2010. However, the mass media repeatedly reported on severe adverse events. The Japanese Ministry of Health, Labor and Welfare suspended proactive recommendations for HPV vaccines in June 2013. Japan’s HPV vaccination rate dropped from 70% to less than 1% in 2017. We examined cervical cancer screening results in terms of abnormal cytology, histology, and HPV vaccination status among 11,903 women aged 20 to 25 y in the fiscal year 2015. The overall rate of HPV vaccination was 26.1% (3,112/11,903). Regarding cytology, the rate of atypical squamous cells of undetermined significance (ASC-US) or worse was 3.3% (103/3,112) in women who received HPV vaccination (vaccine (+) women) and 5.6% (496/8,791) in women who did not (vaccine (-) women). The rate of high-grade squamous intraepithelial lesion (HSIL) or worse was 0.26% (8/3,112) in vaccine (+) women and 0.81% (72/8,791) in vaccine (-) women. Regarding histology, the rate of cervical intraepithelial neoplasia 1 or worse (CIN1+) was 1.4% (42/3,112) in vaccine (+) women and 2.1% (178/8,791) in vaccine (-) women. The rates of CIN2+ and CIN3+ were similar regardless of vaccination. We found a significantly lower incidence of CIN in vaccine (+) women. These results suggest that the resumption of recommending HPV vaccination as primary prevention for cervical cancer is needed in Japan.

The title compounds, 5-(2H-1,3-benzodioxol-5-yl)-N-cyclo­hexyl­penta-2,4-dienamide, (I), and 5-(2H-1,3-benzodioxol-5-yl)-1-(pyrrolidin-1-yl)penta-2,4-dien-1-one (II), are derivatives of piperine, which is known as a pungent component of pepper. Their geometrical parameters are similar to those of the three polymorphs of piperine, which indicate conjugation of electrons over the length of the mol­ecules. The extended structure of (I) features N—H⋯O amide hydrogen bonds, which generate C(4) [010] chains. The crystal of (II) features aromatic π–π stacking, as for two of three known piperine polymorphs., The title compounds, 5-(2H-1,3-benzodioxol-5-yl)-N-cyclo­hexyl­penta-2,4-dienamide, C18H21NO3 (I), and 5-(2H-1,3-benzodioxol-5-yl)-1-(pyrrolidin-1-yl)penta-2,4-dien-1-one C16H17NO3 (II), are derivatives of piperine, which is known as a pungent component of pepper. Their geometrical parameters are similar to those of the three polymorphs of piperine, which indicate conjugation of electrons over the length of the mol­ecules. The extended structure of (I) features N—H⋯O amide hydrogen bonds, which generate C(4) [010] chains. The crystal of (II) features aromatic π–π stacking, as for two of three known piperine polymorphs.

Background We evaluated the efficacy of intraperitoneal (IP) carboplatin in combination with dose-dense paclitaxel (ddTCip) for suboptimal residual ovarian cancer. Methods This was a phase 2 study to evaluate ddTCip. Patients with stage II–IV ovarian carcinoma, who underwent primary cytoreductive surgery and had radiologically evaluable disease after surgery, were eligible to participate in this study. IP carboplatin (AUC = 6) was administered on day 1, and intravenous paclitaxel (80 mg/m2) was administered on days 1, 8 and 15. The primary endpoint was response rate. Secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. Interval- debulking surgery followed by the same regimen was allowed when indicated. Results A total of 117 patients were considered eligible for this study prior to surgery and temporarily registered. Of the 117 patients, 76 patients met the inclusion criteria and were enrolled in this study. Fifty-nine (83.1%) patients had objective clinical responses. Median PFS and OS were 18.3 and 55.5 months, respectively. Sixty-four (84.2%) patients had grade 3/4 neutropenia, 43 (56.5%) patients had anaemia and 17 (22.4%) patients had thrombocytopenia. Port-related adverse events occurred in nine (11.8%) patients. Conclusions Front-line chemotherapy with ddTCip therapy appears safe and effective, even for patients with suboptimal residual ovarian cancer. Trial registration UMIN Clinical Trials Registry (ID: UMIN000001713) on February 16th, 2009.

The effect of ultrasonic irradiation on the optical properties of single-walled carbon nanotubes (SWNTs) was investigated. Upon sonication in D2O in the presence of sodium dodecylbenzene sulfonate (SDBS) under air, red-shifted photoluminescence (PL) peaks at ∼1043 and ∼1118 nm were observed from the aqueous suspensions of (6,4) and (6,5)SWNTs, accompanied by a decrease in the intensity of the intrinsic PL peaks. Upon sonication with SDBS under an Ar atmosphere, the rate of spectral change increased with the sonication time and new PL peaks emerged at 1043, 1118, and 1221 nm. Meanwhile, upon the addition of 1-butanol, the PL peaks emerged only at 1043 nm and 1118 nm, while the emergence of the peak at 1221 nm was inhibited. On the other hand, a suspension with highly dispersed SWNTs was obtained upon sonication in the presence of sodium cholate without any change in the intrinsic optical properties of SWNTs. These experimental results reveal that the PL characteristics of SWNTs can be controlled by controlling the sonication conditions such as the type of surfactant used, the concentration of SWNTs, reaction environment, and the presence of an inhibitor such as 1-butanol.

Daidzein, an aglycone-type isoflavone, is useful in the prevention of atherosclerotic cardiovascular diseases. However, the solubility of daidzein remains relatively low even with pharmaceutical interventions (e.g., γ-cyclodextrin inclusion complex). In the present study, daidzein-cyclodextrin-metal organic framework solid dispersion complexes were prepared by the solvent evaporation method. The physicochemical properties of the complex and its effect on the solubility of daidzein were evaluated. The enhancement effect of a cyclodextrin-metal organic framework on the antioxidant properties of daidzein was verified using a diphenyl-picrylhydrazyl radical scavenging test. Powder X-ray diffraction results showed that the characteristic diffraction peaks of daidzein and cyclodextrin-metal organic framework disappeared and new peaks (2θ = 7.1°, 16.5°) were observed. FT-IR measurements showed that the peak derived from the carbonyl group of daidzein shifted to the lower wavenumber. NOESY 1H-1H NMR showed cross peaks at the proton on the resorcinol side of daidzein and the proton (H-5, H-6) in a cyclodextrin-metal organic framework. Dissolution rate of daidzein at 5 min in distilled water was 0.06% for daidzein alone while the daidzein inclusion complex was about 100%. When fasted state simulated intestinal fluid was used, the dissolution rate of the daidzein complex was about 71% compared with that of daidzein alone (~ 3.0%) at 5 min. The daidzein inclusion complex improved the antioxidant capacity to ~ 1.3 times (17.8 µg/mL) compared to the IC50 of daidzein alone (22.9 µg/mL). Preparations of cyclodextrin-metal organic framework inclusion complexes will be a platform in developing pharmaceutical formulations to enhance the bioavailability and activity of drugs.

OBJECTIVE In Japan, no region has introduced primary HPV testing for cervical cancer screening. We assessed the diagnostic value and possible harm of HPV testing in Japan. METHODS This cross-sectional study with historical controls used cytology-based screening and co-testing data in Japan. As surrogate indicators of possible harm, colposcopy referral rate and cervical intraepithelial neoplasm (CIN) 1 detection rates were calculated. As surrogate indicators with diagnostic values, the detection rates of CIN2 or greater (CIN2+) and CIN3+ were calculated. RESULTS The data of 297 970 women (182 697 for cytology-based, 115 273 for co-testing) were examined. The detection rates of CIN1, CIN2+, and CIN3+ were significantly higher in the co-testing group than in the cytology-based group (P

The ribosome-targeted antifungal agent hygromycin B (HygB) alters the secondary metabolite profiles of fungi. Hypoxylon truncatum NBRC 32353 fermented in the presence of hygromycin B in barley medium activated secondary metabolite synthesis. A new benzaldehyde derivative truncaaldehyde (1) was obtained, along with thirteen known compounds (2–14). The structures of the new compounds were revealed using NMR and single-crystal X-ray crystallography. The total synthesis of (±)-1 was achieved using a four-step sequence, and chiral separation was accomplished. The isolated compounds were tested for their monoamine oxidase (MAO) -A and -B inhibitory activities, with six compounds ((±)-1, 4, 5, 7, 8, and 10) showing inhibitory activity.

The single-step regio- and stereoselective platinum-catalyzed reactions of [60]fullerene with a series of 9-ethynyl-9H-fluoren-9-yl carboxylates afforded fullerene–fluorene dyads in their [2 + 2] c...

ObjectiveTo establish new criteria for the omission of lymphadenectomy in patients with endometrioid carcinoma.Methods We retrospectively reviewed 185 cases of histologically confirmed endometrioid carcinoma by hysterectomy at Jichi Medical University Hospital between January 2006 and December 2011. We reviewed patient medical records to detect risk factors for lymph node metastasis to identify the optimum criteria for lymphadenectomy omission.ResultsUnivariate analysis revealed risk factors for lymph node metastasis to be a large tumor size (volume index ≥40 cm³) (p2 cm (p=0.0003), myometrial invasion ≥50% based on pre-operative MRI (p=0.0366), elevated serum CA125 (pre-menopausal value ≥70 U/mL, post-menopausal value ≥25 U/mL) (p=0.0004), and lymphadenopathy on pre-operative CT scans (p=0.0002). Multivariate analysis indicated that tumor volume index, tumor diameter, elevated serum CA125, and CT scans positive for lymphadenopathy were independent risk factors for lymph node metastasis. Thus, we set tumor diameter >2 cm, elevated serum CA125, and CT scans positive for lymphadenopathy as risk factors. In cases with no risk factors, the rate of lymph node metastasis was 2.1%, which rose to 8.9%, 30.4%, and 58.3% for those with one, two, and three risk factors, respectively. The rate of para-aortic lymph node metastasis rose from 0% to 2.5%, 10.9%, and 41.7% among those with zero, one, two, and three risk factors, respectively.ConclusionsWe propose that lymphadenectomy can be omitted in cases of endometrioid carcinoma that do not have any of the following risk factors: tumor diameter >2 cm, elevated serum CA125, and a CT scan positive for lymphadenopathy. We believe that these new criteria will limit inter-institutional differences as they are all objective factors. Further, they are useful in predicting lymph node metastasis, including para-aortic lymph node metastasis, based on the number of risk factors present.

Background: One of the features of cervical cancer screening using the combination of cytology and human papillomavirus (HPV) testing is the triage for atypical squamous cells of undetermined significance (ASC-US). The effectiveness of the triage has been recognized widely. However, there are few reports evaluating this triage process in Japan. Material and Methods: We retrospectively examined the results of cytology and HPV co-testing for cervical cancer screening in the Oyama area of Tochigi Prefecture between 2012 and 2014. Women who were ASC-US/HPV positive and had cytologic abnormalities [low-grade squamous intraepithelial lesions (LSIL) or worse] were examined by colposcopy. The results of the colposcopy testing were evaluated. In addition, we also examined the results of those who underwent co-testing a year after a ASC-US/HPV-negative result. Results: A total of 21,342 women received their first screening test during the study period, with 542 (2.5%) found to have ASC-US. Of the ASC-US-positive women, 289 (53.3%) were also HPV positive. The prevalence of CIN+ (cervical intraepithelial neoplasia or higher) in the ASC-US/HPV-positive group was 63.2%, with 81.8%, 16.4% and 4.8%. showing CIN 1, CIN 2 and CIN 3+, respectively. The prevalence of CIN+ in the LSIL group was 66.8%, with the majority having a low risk CIN 1 (76.6%) compared to CIN 2 (18.6%), and CIN 3+ (4.8%). No significant difference was observed between the LSIL and ASC-US/ HPV-positive groups. The prevalence of women diagnosed with CIN in the ASC-US/HPV-negative group, following co-testing a year after colposcopy was low (3%). Conclusions: The ASC-US/HPV-positive group was comparable to the LSIL group in terms of prevalence of CIN+ lesions. Furthermore, low CIN prevalence after one year in the ASCUS/ HPV-negative group provides confirmation that the screening interval could be extended. The application of HPV triage (which is routine in other countries) to identify these groups would be of benefit in Japan.

The reaction of the C60 radical anion (C60˙−) with α-bromo-1,3-dicarbonyl compounds selectively afforded the methanofullerene derivatives. The reaction with benzyl halide and 1,2-bis(dihalomethyl)benzene afforded the corresponding 1,4-dibenzylated C60 derivative and cycloaddition product, respectively. The possible mechanisms for the formation of the fullerene adducts are proposed.

Aim To clarify incidence and clinical features of treatment-related leukemia (TRL) due to taxane/platinum therapy in gynecological cancer patients. Methods We conducted a retrospective study of gynecological cancer patients who were diagnosed at facilities participating in the Gynecologic Oncology Trial and Investigation Consortium and started only taxane/platinum therapy as chemotherapy between 2002 and 2006. Results The site of the primary lesion was the ovary in 124, endometrium in 37, and uterine cervix in 4. The regimen of chemotherapy was paclitaxel (T) + carboplatin (C) therapy in 134 and others in 31 patients. The cumulative incidence was 2.4% (4/165), and the incidence was 2.9/1,000 person-years. All four cases were acute myeloid leukemia. The average total doses of T and C in patients without TRL were 1,693 (SD 1,050) and 4,170 (SD 2,423) mg. For TRL patients, the total T and C doses were, respectively, 1,555 and 3,540 mg, 1,620 and 4,200 mg, 2,130 and 4,700 mg, 3,220 mg and 8,310 mg. The fourth patient received additional 2,415 mg of docetaxel and 2,155 mg of nedaplatin. The intervals from the primary chemotherapy to the onset of TRL were 27, 34, 67, and 114 months. Three patients had no evidence of ovarian cancer. Three patients died of TRL at 4 days, 5 months, and 11 months, one patient remained in remission at 25 months after diagnosis of TRL. Conclusion Patients receiving taxane/platinum therapy should undergo long-term follow-up with attention to the development of TRL, even if the gynecologic malignant cancer is in remission.

Ellagic acid (EA), a natural polyphenol found in berries, has high antioxidant capacity. This study aimed to improve EA solubility by complex formation with urea (UR) using solvent evaporation method and evaluate its solubility, antioxidant capacity, and physical properties. The solubility test (25 °C, 72 h) showed that the solubility of EVP (EA/UR = 1/1) was approximately two-fold higher than that of EA (7.13 µg/mL versus 3.99 µg/mL). Moreover, the IC50 values of EA and EVP (EA/UR = 1/1) (1.50 µg/mL and 1.30 µg/mL, respectively) showed higher antioxidant capacity of EVP than that of EA. DSC analysis revealed that the UR peak at 134 °C disappeared, and a new endothermic peak was observed at approximately 250 °C for EVP (EA/UR = 1/1). PXRD measurements showed that the characteristic peaks of EA at 2θ = 12.0° and 28.0° and of UR at 2θ = 22.0°, 24.3°, and 29.1° disappeared and that new peaks were identified at 2θ = 10.6°, 18.7°, and 26.8° for EVP (EA/UR = 1/1). According to 2D NOESY NMR spectroscopy, cross-peaks were observed between the -NH and -OH groups, suggesting intermolecular interactions between EA and UR. Therefore, complexation was confirmed in EA/UR = 1/1 prepared by solvent evaporation, suggesting that it contributed to the improvement in solubility and antioxidant capacity of EA., This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

1,2,3,4-Tetrahydroquinolines should be applicable to the development of new pharmaceutical agents. A facile synthesis of 1,2,3,4-tetrahydroquinolines that is achieved by a photoinduced formal [4+2] cycloaddition reaction of acyclic α,β-unsaturated amides and imides with N,N-dialkylanilines under visible-light irradiation, in which a new IrIII complex photosensitizer, a thiourea, and an oxidant act cooperatively in promoting the reaction, is reported. The photoreaction enables the synthesis of a wide variety of 1,2,3,4-tetrahydroquinolines, while controlling the trans/cis diastereoselectivity (>99:1) and constructing contiguous stereogenic centers. A chemoselective cleavage of an acyclic imide auxiliary is demonstrated.

Thirty-five pyridone derivatives were synthesized, with derivatization conducted on polycyclic pyridone scaffolds, including cis- or trans-oxydecalin and other cyclic structures, by domino-Knoevenagel-electrocyclic reactions. The anti-fungal activities of the synthesized compounds were tested against Candida albicans. Ten compounds inhibited hyphal formation without inhibiting growth. Pyridones with anti-hyphal formation activity (4c, 6d, 12a and 12c) were tested for their ability to inhibit biofilm formation. Compound 6d showed both anti-hyphal and biofilm inhibition activity.

Cervical cancer screening has been shifting from primary cytology to primary HPV testing worldwide as primary HPV testing is more sensitive than primary cytology. To the best of our knowledge, the current study is the first in Japan to examine the feasibility of primary HPV testing. One of the disadvantages of this shift is that hrHPV-/≥LSIL/CIN2+ (high-risk HPV negative cancers or pre-cancerous lesions with abnormal cytology results) can be missed. The objectives of the present study are to clarify in detail CIN2+ missed by this shift and to evaluate the feasibility of primary HPV testing in Japan. Data from 115,273 women who underwent co-testing with cytology and HPV testing in cancer screening were used in the current study. The cases with hrHPV-/≥LSIL (‘hrHPV-/≥L-SIL’ include CIN2-, in contrast, ‘hrHPV-/≥L-SIL/CIN2+’ doesn't include CIN2-) were analysed in detail. Women with hrHPV-/≥LSIL comprised 0.3% of the total. The prevalence of CIN2, CIN3, SCC or cervical adenocarcinomas in the lesions with HPV-/≥LSIL was 0.03% in the cancer screening group. Only one case of 14 cervical adenocarcinomas in ≥LSIL was hrHPV-. The prevalence of cancer missed by the shift in patients >50 years of age was significantly higher compared with patients younger than 49 years. In conclusion, the prevalence of CIN2+, which might be missed by the shift from primary cytology to primary HPV testing, was remarkably low in this Japanese cancer screening. The data indicated that primary HPV testing, which was more sensitive for CIN2+ than primary cytology, was a feasible method that can be used in Japan. In particular, primary HPV testing should be introduced for women

An open-cage fullerene bearing an eight-membered ring orifice has been synthesized in one pot by the reaction of C60 with propargylic phosphate in the presence of CuCl. The reaction cascade involves the transformation of the phosphate to the 1,3-dienyl phosphate, which enables the reaction with C60 by [4 + 2] cycloaddition to form the cyclohexene-annulated intermediate, and subsequent intramolecular syn-elimination of the phosphodiester affords the cyclohexadiene-annulated fullerene derivative as the precursor for the open-cage fullerene., Published: April 21, 2020

Additions of adamantylidene (Ad) to M3 N@Ih -C80 (M=Sc, Lu) and Sc3 N@D5h -C80 have been accomplished by photochemical reactions with 2-adamantyl-2,3'-[3H]-diazirine (1). In M3 N@Ih -C80 , the addition led to rupture of the [6,6]- or [5,6]-bonds of the Ih -C80 cage, forming the [6,6]-open fulleroid as the major isomer and the [5,6]-open fulleroid as the minor isomer. In Sc3 N@D5h -C80 , the addition also proceeded regioselectively to yield three major isomeric Ad mono-adducts, despite the fact that there are nine types of C-C bonds in the D5h -C80 cage. The molecular structures of the seven Ad mono-adducts, including the positions of the encaged trimetallic nitride clusters, have been unambiguously determined through single-crystal XRD analyses. Furthermore, results have shown that stepwise addition of Ad to Lu3 N@Ih -C80 affords several Ad bis-adducts, two of which have been isolated and characterized. The X-ray structure of one bis-adduct clearly revealed that the second Ad addition took place at a [6,6]-bond close to an endohedral metal atom. Theoretical calculations have also been performed to rationalize the regioselectivity.

Alkylated single-walled carbon nanotubes (SWNTs) have been thermally treated to determine the influence of substituents and the degree of functionalization on their thermal stability and photoluminescence (PL) properties. Alkylated SWNTs were prepared by treating SWNTs with sodium naphthalenide and alkyl bromide. The defunctionalization of the alkylated SWNTs was monitored by absorption and Raman spectra. Selective recovery of the characteristic absorption and radial breathing mode peaks was observed during the thermal treatment, which indicates that the thermal stability of the alkylated SWNTs decreases with increases in SWNT diameter and degree of functionalization. n-Butylated and phenethylated SWNTs showed higher thermal stability than sec-butylated and benzylated SWNTs for a similar degree of functionalization, respectively. The diameter selectivity and effect of substituents on the thermal elimination reaction were confirmed by density functional theory. In addition, it was shown that the initial degree of functionalization of the alkylated SWNTs, with the alkyl group and degree of functionalization being kept constant after thermal treatment, strongly affects their PL properties; Stokes shift, and PL peak intensity.

Objective Liquid-based cytology has replaced conventional cytology in cervical cancer screening in many countries. However, a detailed comparison of liquid-based cytology with conventional cytology has not been reported in Japan. Therefore, the aim of the study is to evaluate efficacy of liquid-based cytology in Japan. Methods We first evaluated the prevalence of use of liquid-based cytology and then examined the efficacy of liquid-based cytology and conventional cytology for detecting CIN and the rate of unsatisfactory specimens using data from cancer screening collected by the Japanese Cancer Society from FY2011 to FY2014. A Poisson regression model with random effects analyses was used to classify histological outcomes and unsatisfactory specimens using liquid-based cytology compared to conventional cytology. Results A total of 3 815 131 women were analyzed in the study. The rate of liquid-based cytology increased from approximately 8% in FY2011 to 37% in FY2014. Compared to conventional cytology, the detection rates with liquid-based cytology were significantly higher (1.42 times) for CIN1+ [detection rate ratio (DRR) = 1.42, 95% confidence interval (CI) 1.35–1.48, P Conclusions In order to avoid the unsatisfactory specimens in cervical cancer screening, the results of this study did indicate that liquid-based cytology was more useful than conventional cytology in practical standpoints.

The single-step regio- and stereoselective platinum-catalyzed reactions of [60]fullerene with a series of 9-ethynyl-9

To compare the efficacy, safety, and tolerability profiles of pegylated liposomal doxorubicin and carboplatin (PLDC) with those of gemcitabine and carboplatin (GC) for the treatment of patients with platinum-sensitive recurrent ovarian cancer. Ovarian cancer patients with recurrence > 6 months after first-line platinum and taxane-based therapies were randomly assigned to PLDC [pegylated liposomal doxorubicin 30 mg/m2 plus carboplatin area under the curve (AUC) 5 mg/mL/min on day 1] every 4 weeks or GC (gemcitabine 1000 mg/m2 on days 1 and 8 plus carboplatin AUC 4 mg/mL/min on day 1) every 3 weeks for at least 6 cycles. The primary endpoint was progression-free survival, and overall response rate, overall survival, toxicity, and dose administration were secondary endpoints. One-hundred patients (49 PLDC; 51 GC) were randomly assigned. Over a median follow-up of 24 months, the median progression-free survival was 12.0 months (95% CI 9.2–15.0) for PLDC and 9.8 months (8.9–12.3) for GC [HR 0.69 (0.455–1.047)] with a difference of 2.2 months. The response rate was 57.1% (41.0–72.3) for PLDC and 56.4% (39.6–72.2) for GC. No obvious differences in toxicity (G3/4) were noted between arms. The median relative dose intensity of planned dose per week was 88.9% for pegylated liposomal doxorubicin and 53.1% for gemcitabine (p