<p>Supplemental table 2. Differential gene expression and pathway enrichment analysis in placebo responders (excel file) -uploading separately.</p>

Supplemental Figure 3. Validation of RNA seq results of responders by Nanostring nCounter gene expression assay

<p>Supplemental Figure 1. Validation of RNA seq results of responders by Nanostring nCounter gene expression assay.</p>

<p>Supplemental Figure 5. Ki67 Change was not associated with drug concentration in Tumor samples. Tumor samples were available for quantitation from 22 women.</p>

Supplemental table 1. Differential gene expression and pathway enrichment analysis in TPA responders (excel file) -uploading separately.

<p>Supplemental Figure 2. Ki67 Change relative to treatment duration. There was no significant correlation between change in Ki67 and treatment duration, in either TPA or placebo arms.</p>

Supplemental Figure 4. Plots showing changes in serum estradiol (left panel) and serum progesterone (right panel) in three subgroups: placebo, TPA-treated Ki67 responders and TPA-treated Ki67-nonresponders.

<p>Supplemental Figure 1. Validation of RNA seq results of responders by Nanostring nCounter gene expression assay.</p>

Immunoglobulin M (IgM) antibody to hepatitis C core antigen (anti-HCV-core) was tested by enzyme immunoassay against a synthetic peptide representing amino acids 1 to 62 of the core protein. Of 214 patients with different categories of histological activity, 193 (90%) showed positive results for IgM anti-HCV-core, and 207 (97%) had HCV RNA; most cases (186, 87%) had both markers detectable simultaneously. No differences in the frequency of IgM anti-HCV-core were observed with respect to epidemiological, biochemical, or histological parameters. In 175 interferon alfa (IFN-alpha) recipients, and in 39 untreated controls, pretreatment IgM anti-HCV-core frequencies were similar: 28 of 32 (88%) in sustained responders; 55 of 61 (90%) in responders with relapse; 72 of 82 (88%) in nonresponders; and 38 of 39 (97%) in untreated controls. After IFN-alpha therapy, IgM anti-HCV-core levels became undetectable with significantly greater frequency in sustained responders (P = .014); a similar trend was observed for HCV RNA (P < .0001). IgM anti-HCV-core levels decreased after therapy in responders (P < .001) but increased in nonresponders. Fifty-one cases were longitudinally tested in relation to long-term disease outcome. Both markers remained detectable in most nonresponders with persistent liver disease, in most responders before relapse, and in all but one case at the time of biochemical relapse. IgM anti-HCV-core and HCV RNA became undetectable in most sustained responders, but reappeared despite a long-lasting transaminase normalization, behaving as asymptomatic HCV carriers; the possibility that disease reactivation may take place years afterwards cannot be excluded.(ABSTRACT TRUNCATED AT 250 WORDS)

The HEROES study evaluated RPC4046 in adults with active eosinophilic esophagitis (EoE). In this exploratory substudy, we investigated whether RPC4046 modulates epithelial-mesenchymal transition (EMT). Esophageal biopsy sections were taken at baseline and week 16 from 69 patients receiving weekly subcutaneous RPC4046 360 mg (n=26), 180 mg (n=19), or placebo (n=24). Slides were stained by duplex immunofluorescence for e-cadherin and vimentin, counterstained nuclei with DAPI, and scanned at 20x via multispectral digital microscopy. A machine-learning algorithm mapped each slide's epithelial compartment. Nuclear, cytoplasmic, and membrane areas of each epithelial cell were defined and fluorescence intensity of each marker on a per-cell basis was recorded. Endpoints included change from baseline in percentage of vimentin-positive epithelial cells, change in total e-cadherin expression/cell, and change in vimentin:e-cadherin ratio/cell. Change from baseline in mean percentage of vimentin-positive cells was −4.24%, −2.75%, and −0.94% for RPC4046 360 mg, 180 mg, and placebo, respectively (P<0.05, 360 mg vs placebo). Change in mean e-cadherin expression per cell was 101.6, 102.4, and 18.3, respectively (P<0.05, each dose group vs placebo). Change in vimentin:e-cadherin ratio was significantly different from zero for 360 mg (−0.30) and 180 mg (−0.18) (P<0.05). Similar effects for all markers were observed in each esophageal sampled region. RPC4046 significantly improved esophageal tissue EMT markers in patients with EoE, with a greater effect observed with 360 mg. Results support the hypothesis that prevention of IL-13 binding to receptor subtypes IL-13Rα1 and IL-13Rα2 favorably impacts inflammatory and remodeling pathways and may reduce development of esophageal fibrostenosis in EoE.

Introduction: Numerous epidemiological studies have established that a completed pregnancy is protective against breast cancer. However, the mechanisms through which pregnancy induces persistent changes in the breast, which translate into decreased cancer susceptibility, are poorly understood. One such change might be the reduction of ERα positive cells after pregnancy, supported by animal models and some evidence in the human breast. We recently reported that pregnancy causes a persistent downregulation of ERα expression at the mRNA level in the human breast that persists for up to 10 years; in addition, we reported a trend towards downregulation of Her2/neu (Asztalos et al. 2010). The purpose of the present study was to determine whether these mRNA findings were corroborated at the protein level by examining ERα and Her2/neu expression via immunohistochemistry (IHC) in the same set of human breast tissues. Patients and Methods: Women Results: We found a statistically significant lower Her2/neu intensity in the recent pregnancy group compared to the other two groups (average intensity RP=127 vs DP=138 and NP=138, p Conclusions: This is one of few studies to investigate the influence of pregnancy on the expression of two important breast cancer biomarkers, ERα and Her2/neu, in benign breast tissue. The study differentiated between recent and distant pregnancy and thus was able to look for persistent changes that might occur. Although we did not find the same differences at the protein level that we saw at the mRNA level, this could be attributed to the lower sensitivity of the IHC technique compared to real time PCR coupled with the small number of samples that were used. Given the strength of epidemiological data, further studies are warranted. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3737. doi:10.1158/1538-7445.AM2011-3737

We examined the association between self‐reported consumption of fruits and vegetables and prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Data on food consumption and complete follow‐up for cancer incidence were available for 130,544 men in 7 countries recruited into EPIC between 1993 and 1999. After an average of 4.8 years of follow‐up, there were 1,104 incident cases of prostate cancer. The associations of consumption of total fruits, total vegetables, cruciferous vegetables and combined total fruits and vegetables with prostate cancer risk were examined using Cox regression, stratified for recruitment center and adjusted for height, weight and energy intake. There was a wide range in consumption of fruits and vegetables: mean intakes (g/day) in the bottom and top fifths of the distribution, as estimated from 24‐hr recalls in a subsample of participants, were 53.2 and 410.7 for fruits, 97.1 and 242.1 for vegetables and 169.0 and 633.7 for fruits and vegetables combined. No significant associations between fruit and vegetable consumption and prostate cancer risk were observed. Relative risks (95% confidence intervals) in the top fifth of the distribution of consumption, compared to the bottom fifth, were 1.06 (0.84–1.34) for total fruits, 1.00 (0.81–1.22) for total vegetables and 1.00 (0.79–1.26) for total fruits and vegetables combined; intake of cruciferous vegetables was not associated with risk. These results suggest that total consumption of fruits and vegetables is not associated with the risk for prostate cancer. © 2003 Wiley‐Liss, Inc.

BACKGROUND:Overdiagnosis of clinically insignificant prostate cancer is considered a major potential drawback of prostate-specific antigen (PSA) screening. Quantitative estimates of the magnitude of this problem are, however, lacking. We estimated rates of prostate cancer overdiagnosis due to PSA testing that are consistent with the observed incidence of prostate cancer in the United States from 1988 through 1998. Overdiagnosis was defined as the detection of prostate cancer through PSA testing that otherwise would not have been diagnosed within the patient's lifetime.METHODS:We developed a computer simulation model of PSA testing and subsequent prostate cancer diagnosis and death from prostate cancer among a hypothetical cohort of two million men who were 60-84 years old in 1988. Given values for the expected lead time--that is, the time by which the test advanced diagnosis--and the expected incidence of prostate cancer in the absence of PSA testing, the model projected the increase in population incidence of prostate cancer associated with PSA testing. By comparing the model-projected incidence with the observed incidence derived from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registry data, we determined the lead times and corresponding overdiagnosis rates that were consistent with the observed data.RESULTS:SEER data on prostate cancer incidence from 1988 through 1998 were consistent with overdiagnosis rates of approximately 29% for whites and 44% for blacks among men with prostate cancers detected by PSA screening.CONCLUSIONS:Among men with prostate cancer that would be detected only at autopsy, these rates correspond to overdiagnosis rates of, at most, 15% in whites and 37% in blacks. The observed trends in prostate cancer incidence are consistent with considerable overdiagnosis among PSA-detected cases. However, the results suggest that the majority of screen-detected cancers diagnosed between 1988 and 1998 would have presented clinically and that only a minority of cases found at autopsy would have been detected by PSA testing.