We present the results of a dust reverberation survey for 17 nearby Seyfert 1 galaxies, which provides the largest homogeneous data collection for the radius of the innermost dust torus. A delayed ...response of the K-band light curve after the V-band light curve was found for all targets, and 49 measurements of lag times between the flux variation of the dust emission in the K band and that of the optical continuum emission in the V band were obtained by the cross-correlation function analysis and also by an alternative method for estimating the maximum likelihood lag. We discuss the possible origins of the intrinsic scatter of the dust lag-luminosity correlation, which was estimated to be approximately 0.13 dex, and we find that the difference of internal extinction and delayed response of changes in lag times to the flux variations could have partly contributed to intrinsic scatter.
We have recently completed a 64-night spectroscopic monitoring campaign at the Lick Observatory 3 m Shane telescope with the aim of measuring the masses of the black holes in 12 nearby (z < 0.05) ...Seyfert 1 galaxies with expected masses in the range {approx}10{sup 6}-10{sup 7} M{sub sun} and also the well-studied nearby active galactic nucleus (AGN) NGC 5548. Nine of the objects in the sample (including NGC 5548) showed optical variability of sufficient strength during the monitoring campaign to allow for a time lag to be measured between the continuum fluctuations and the response to these fluctuations in the broad H{beta} emission, which we have previously reported. We present here the light curves for the H{alpha}, H{gamma}, He II {lambda}4686, and He I {lambda}5876 emission lines and the time lags for the emission-line responses relative to changes in the continuum flux. Combining each emission-line time lag with the measured width of the line in the variable part of the spectrum, we determine a virial mass of the central supermassive black hole from several independent emission lines. We find that the masses are generally consistent within the uncertainties. The time-lag response as a function of velocity across the Balmer line profiles is examined for six of the AGNs. We find similar responses across all three Balmer lines for Arp 151, which shows a strongly asymmetric profile, and for SBS 1116+583A and NGC 6814, which show a symmetric response about zero velocity. For the other three AGNs, the data quality is somewhat lower and the velocity-resolved time-lag response is less clear. Finally, we compare several trends seen in the data set against the predictions from photoionization calculations as presented by Korista and Goad. We confirm several of their predictions, including an increase in responsivity and a decrease in the mean time lag as the excitation and ionization level for the species increases. Specifically, we find the time lags of the optical recombination lines to have weighted mean ratios of {tau}(H{alpha}):{tau}(H{beta}):{tau}(H{gamma}):{tau}(He I):{tau}(He II) = 1.54:1.00:0.61:0.36:0.25. Further confirmation of photoionization predictions for broad-line gas behavior will require additional monitoring programs for these AGNs while they are in different luminosity states.
We examine whether the spectral energy distribution of UV continuum emission of active galactic nuclei changes during flux variation. We used multi-epoch photometric data of QSOs in Stripe 82 ...observed by the Sloan Digital Sky Survey (SDSS) Legacy Survey and selected 10 bright QSOs observed with high photometric accuracies, in the redshift range of z = 1.0-2.4 where strong broad emission lines such as Ly Delta *a and C IV do not contaminate SDSS filters, to examine spectral variation of the UV continuum emission with broadband photometries. All target QSOs showed clear flux variations during the monitoring period 1998-2007, and the multi-epoch flux data in two different bands obtained on the same night showed a linear flux-to-flux relationship for all target QSOs. Assigning the flux in the longer wavelength to the x-axis in the flux-to-flux diagram, the x-intercept of the best-fit linear regression line was positive for most targets, which means that their colors in the observing bands become bluer as they become brighter. Then, the host-galaxy flux was estimated on the basis of the correlation between the stellar mass of the bulge of the host galaxy and the central black hole mass; the latter was estimated on the basis of the luminosity scaling relations for C IV or Mg II emission lines and their line width. We found that the longer-wavelength flux of the host galaxy was systematically smaller than that of the fainter extension of the best-fit regression line at the same shorter-wavelength flux for most targets. This result strongly indicates that the spectral shape of the continuum emission of QSOs in the UV region (~1400-3600 A in rest-frame wavelength) usually becomes bluer as it becomes brighter. The multi-epoch flux data in the flux-to-flux diagram were found to be consistent with the wavelength-dependent amplitude of variation presented in Vanden Berk et al., which showed a larger amplitude of variation in shorter wavelengths. We also found that the multi-epoch flux-to-flux plots could be fitted well with the standard accretion disk model changing the mass accretion rate with a constant black hole mass for most targets. This finding strongly supports the standard accretion disk model for UV continuum emission of QSOs.
Background
The first-line chemotherapy for patients with
RAS
and
BRAF
wild-type metastatic colorectal cancer (mCRC) commonly involves cytotoxic regimens, such as FOLFOX and FOLFIRI, combined with ...epidermal growth factor receptor (EGFR) antibodies. When progression occurs following anti-EGFR antibody-combined chemotherapy, anti-angiogenic inhibitors can be used as second-line treatment. Although randomized controlled trials have shown that anti-angiogenic inhibitors bevacizumab, ramucirumab, and aflibercept (AFL) carry survival benefit when combined with FOLFIRI as second-line chemotherapy, such trials did not provide data on patients with mCRC refractory to anti-EGFR antibody-combined chemotherapy. Therefore, our group planned a multicenter, nonrandomized, single-arm, prospective, phase II study to investigate the safety and efficacy of FOLFIRI plus AFL as a second-line chemotherapy for patients with mCRC refractory to oxaliplatin-based chemotherapy combined with anti-EGFR antibodies.
Methods
FOLFIRI (irinotecan 180 mg/m
2
,
l
-leucovorin 200 mg/m
2
, bolus 5-FU 400 mg/m
2
, and infusional 5-FU 2400 mg/m
2
/46 h) and AFL (4 mg/kg) will be administered every 2 weeks until progression or unacceptable toxicities occur. The primary endpoint will be the 6-month progression-free survival (PFS) rate, whereas the secondary endpoints will include overall survival, PFS, response rate, disease control rate, adverse events, and relative dose intensity for each drug. A sample size of 41 participants will be required. This study will be sponsored by the Non-Profit Organization Hokkaido Gastrointestinal Cancer Study Group and will be supported by a grant from Sanofi.
Discussion
There is only an observational study reporting data on FOLFIRI plus AFL for patients with mCRC who previously received anti-EGFR antibodies; therefore, a prospective clinical trial is needed. This study will prospectively evaluate the efficacy and safety of FOLFIRI plus AFL in patients with mCRC who are resistant to anti-EGFR antibodies and have limited data. Moreover, this study will reveal predictive biomarkers for AFL-based chemotherapy.
Clinical trial registration
Japan Registry of Clinical Trials, jRCTs011190006. Registered 19 November, 2019,
https://jrct.niph.go.jp/latest-detail/jRCTs011190006
.
We examine whether the spectral energy distribution of optical continuum emission of active galactic nuclei (AGNs) changes during flux variation, based on accurate and frequent monitoring ...observations of 11 nearby Seyfert galaxies and QSOs carried out in the B, V, and I bands for seven years by the MAGNUM telescope. The multi-epoch flux data in any two different bands obtained on the same night show a very tight linear flux-to-flux relationship for all target AGNs. The flux of the host galaxy within the photometric aperture is carefully estimated by surface brightness fitting to available high-resolution Hubble Space Telescope images and MAGNUM images. The flux of narrow emission lines in the photometric bands is also estimated from available spectroscopic data. We find that the non-variable component of the host galaxy plus narrow emission lines for all target AGNs is located on the fainter extension of the linear regression line of multi-epoch flux data in the flux-to-flux diagram. This result strongly indicates that the spectral shape of AGN continuum emission in the optical region ({approx}4400-7900 A) does not systematically change during flux variation. The trend of spectral hardening that optical continuum emission becomes bluer as it becomes brighter, which has been reported by many studies, is therefore interpreted as the domination of the variable component of the nearly constant spectral shape of an AGN as it brightens over the non-variable component of the host galaxy plus narrow lines, which is usually redder than AGN continuum emission.
The Lick AGN Monitoring Project targeted 13 nearby Seyfert 1 galaxies with the intent of measuring the masses of their central black holes using reverberation mapping. The sample includes 12 galaxies ...selected to have black holes with masses roughly in the range 106-107 M, as well as the well-studied active galactic nucleus (AGN) NGC 5548. In conjunction with a spectroscopic monitoring campaign, we obtained broadband B and V images on most nights from 2008 February through 2008 May. The imaging observations were carried out by four telescopes: the 0.76 m Katzman Automatic Imaging Telescope, the 2 m Multicolor Active Galactic Nuclei Monitoring telescope, the Palomar 60 inch (1.5 m) telescope, and the 0.80 m Tenagra II telescope. Having well-sampled light curves over the course of a few months is useful for obtaining the broad-line reverberation lag and black hole mass, and also allows us to examine the characteristics of the continuum variability. In this paper, we discuss the observational methods and the photometric measurements, and present the AGN continuum light curves. We measure various variability characteristics of each of the light curves. We do not detect any evidence for a time lag between the B- and V-band variations, and we do not find significant color variations for the AGNs in our sample.
The aim of the present study was to investigate changes in emotional state and the relationship between emotional state and demographic/clinical factors and coping style among gynecologic patients ...undergoing surgery. Using the Japanese version of the Profile of Mood States (POMS), 90 patients (benign disease: 32, malignancy: 58) were examined on three occasions: before surgery, before discharge, and 3 months after discharge. They were also examined using the Coping Inventory for Stressful Situations (CISS) on one occasion before discharge. The scores for the subscales depression, anger, and confusion were the highest after discharge while those for anxiety were the highest before surgery. The average scores of the POMS subscales for all subjects were within the normal range. With regard to the relationship between these emotional states and other factors, multiple regressions showed that the principal determinants of anxiety before surgery were religious belief, psychological symptoms during hospitalization and emotion‐oriented (E) coping style; further, it was found that depression after discharge could be explained by chemotherapy, duration of hospitalization, and E coping style. The principal determinants of anger after discharge and vigor before surgery were length of education and E coping style, and severity of disease, chemotherapy, E coping style and task‐oriented coping style, respectively. Those of post‐discharge fatigue and confusion were length of education, psychological symptoms, and E coping style. In summary it is suggested that the following should be taken into account in patients undergoing gynecologic surgery: anxiety before surgery, depression, anger, and confusion after surgery, including coping styles.
Background: Previously we reported that immunohistochemical examination of p53, bcl-2, glutathione S-transferase-π (GST-π), thymidylate synthase (TS) and vascular endothelial growth factor (VEGF) in ...biopsy samples was a useful method for predicting clinical outcome of gastric cancer patients treated with 5-fluorouracil and cisplatin. Here, we investigated if these biological markers can predict chemoresponse and survival of unresectable gastric cancer patients treated with irinotecan and cisplatin. Methods: The subjects were 55 unresectable gastric cancer patients treated with irinotecan (70 mg/m2, Days 1 and 15) and cisplatin (80 mg/m2, Day 1). Expression of p53, bcl-2, VEGF was examined immunohistochemically in biopsy samples. Results: The overall response rate and the median survival time were 55% (30/55) and 321 days, respectively. Thirty patients with intestinal-type adenocarcinoma survived longer than 25 patients with diffuse-type (median survival time: 446, 259 days, P = 0.013). The favorable phenotypes for chemoresponse were p53-negative, bcl-2-negative and VEGF-positive, which were in accordance with previous findings. The response rate was significantly correlated with the total number of these favorable phenotypes (P = 0.043). The 39 patients having 2 or 3 favorable phenotypes (p53-negative, bcl-2-negative and VEGF-positive) survived longer than the remaining 16 patients (median survival time: 444, 259 days, P = 0.021). In the Cox model, the number of the favorable phenotypes showed a tendency to correlate with survival after adjustment for potentially prognostic factors such as histological type or performance status (P = 0.070). Conclusions: Immunohistochemical examination of biological markers may be useful in predicting the clinical outcome of unresectable gastric cancer patients treated with irinotecan and cisplatin.
Chemoradiotherapy is a useful treatment strategy in patients with locally advanced cancers. In particular, combination of 5-fluorouracil (5-FU) with X-ray irradiation is effective for the treatment ...of some types of gastrointestinal cancers. We investigated the antitumor effects of combination treatment with X-ray and S-1, a unique formulation of 5-FU, on human cancer xenografts in nude mice and compared the efficacy of this treatment to that of radiotherapy combined with cisplatin, UFT, another oral 5-FU prodrug, and intravenous 5-FU. Tumors implanted into the left hind legs of mice were treated with a dose of 2 or 5 Gy X-ray irradiation on days 1 and 8, and S-1, UFT and 5-FU were administered for 14 days. The efficacy of combined treatment with 8.3 mg/kg S-1 and 2 Gy X-ray irradiation in treating non-small cell lung cancer xenografts (Lu-99 and LC-11) was significantly higher than that of treatment with S-1 alone or 2 Gy X-ray irradiation alone, and the antitumor activity of combined treatment was similar to that of 5 Gy X-ray irradiation alone. Although 8.3 mg/kg S-1 and 17.5 mg/kg UFT had equivalent antitumor activity; the antitumor efficacy of combination treatment with S-1 and 2 Gy X-ray irradiation on LC-11 tumors was significantly higher than that of combination treatment with UFT and 2 Gy X-ray irradiation. Combination treatment with S-1 and X-ray irradiation was also more effective against pancreatic tumors than combination treatment with intravenous 5-FU and X-ray irradiation. To elucidate the reason for the increased antitumor efficacy of combination treatment with S-1 and X-ray irradiation, the antitumor effect of gimeracil, one of the components of S-1, was tested in combination with 2 Gy X-ray irradiation. These experiments demonstrated that gimeracil enhanced the efficacy of X-ray irradiation against lung as well as head and neck cancer xenografts in a dose-dependent manner. Furthermore, we observed decreased expression of γ-H2AX protein, a marker of DNA repair, in LC-11 tumors treated with X-ray irradiation and gimeracil compared to that observed in tumors treated with X-ray irradiation alone, suggesting that gimeracil may inhibit rapid repair of X-ray-induced DNA damage in tumors. The present study suggests that chemoradiotherapy using S-1 acts through a novel mechanism and may prove useful in treating patients with locally advanced cancers whose disease progression is difficult to control using chemotherapy alone.
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