Predictive value of apoptosis, proliferation, HER-2, and topoisomerase IIalpha for anthracycline chemotherapy in locally advanced breast cancer

Purpose. Laboratory evidence indicates that tumor growth depends on the balance between cell proliferation and cell death, and many anticancer agents may exert their therapeutic effect by decreasing proliferation and increasing apoptosis. Additionally, clinical observations indicate that overexpression of HER-2 or topoisomerase II alpha ( topo II alpha) may be predictors of better response to anthracyclines in breast cancer. The objective of this study was to determine if proliferation ( Ki-67), apoptosis ( TUNEL), and expression of HER-2 and topo II alpha are affected by anthracycline treatment, and if these molecular markers predict anthracycline responsiveness. Experimental design. Thirty-three women with primary breast tumors >= 3 cm received either doxorubicin ( 75 mg/ m(2)) or epirubicin ( 120 mg/ m(2)) for 4 cycles before surgery. Clinical response was evaluated after 4 cycles of treatment. Changes in molecular markers were assessed from core needle biopsy taken before treatment (D0), at 24 - 48 h (Dl) and on day 7 (D7) while on treatment, and from the surgical specimen excised on day 84 (D84) after the fourth cycle of chemotherapy. Results. The overall clinical response rate was 51% (17 of 33 patients), with a 12% complete clinical response rate ( 4 of 33 patients). There were trends for tumors with higher apoptosis and topo IIa at baseline ( D0) to be more responsive to anthracyclines, p = 0.1 and p = 0.08, respectively. Median apoptosis increased from D0 to Dl ( p = 0.06) while median Ki-67 decreased ( p = 0.07). Overall, expression of HER-2 remained stable throughout the chemotherapy administration. By Day 84, topo II alpha had significantly decreased from baseline in responders, while it increased in non-responders, p = 0.03. Conclusions. In human primary breast cancer, anthracycline treatment causes an early increase in apoptosis and a decrease in proliferation. In this pilot study, higher apoptosis and topo II alpha a levels in primary tumors were associated with greater responsiveness to anthracyclines, and topo II alpha levels declined in responsive tumors

Nucleotide variation, haplotype structure, and association with end-stage renal disease of the human interleukin-1 gene cluster

A dense gene-based SNP map was constructed across a 360-kb region containing the interleukin-1 gene cluster (IL1A, IL1B, and IL1RN), focusing on IL1RN. In total, 95 polymorphisms were confirmed or identified primarily by direct sequencing. Polymorphisms were precisely mapped to completed BAC and genomic sequences spanning this region. The polymorphisms were typed in 443 case-control subjects from Caucasian and African American groups. Consecutive pair-wise marker linkage disequilibrium was not strictly correlated with distance and ranged from D′ = 0.0079 to 1.000 and D′ = 0.0521 to 1.0000 in Caucasians and African Americans, respectively. Single markers and haplotypes in IL1 cluster genes were evaluated for association with end-stage renal disease (ESRD). Eleven SNPs show some evidence of association with ESRD, with the strongest associations in two IL1A variants, one SNP, rs1516792-3, in intron 5 (p = 0.0015) and a 4-bp insertion/deletion within the 3′UTR, rs16347-2 (p = 0.0024), among African Americans with non-T2DM-associated ESRD

The Psychological Science Accelerator’s COVID-19 rapid-response dataset

In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data

The Psychological Science Accelerator’s COVID-19 rapid-response dataset

In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data

AMORPHOUS SILICON IN PHOTOTHERMAL CONVERSION

Efficient conversion of solar energy into heat requires a spectrally selective surface to function as a one-way valve between the incident radiation and heat transfer system. The tandem action of a solar absorber overlying an infrared reflector gives this action, provided the absorber is transparent in the thermal infrared /l/. Our group has fabricated such tandem stacks, durable at high temperatures, by depositing both absorber and reflector layers by Chemical Vapor Deposition (CVD), a method of economic promise for large-scale production /2, 3/. Although the initial work used polycrystalline silicon as the solar absorber, it was realized that amorphous silicon could raise the solar absorptance of the CVD tandem stacks /4/. However, there existed a major obstacle to its use : amorphous silicon deposited by the two most widely used methods of physical vapor deposition, evaporation and sputtering, crystallized near 550 °C /5/. This temperature is too low for photothermal energy converter operation. It is also so low that the pyrolytic decomposition of silane, the basic reaction for producing silicon CVD, proceeds at an infinitesimal rate. In an attempt to pass through the amorphous-to-crystalline transition temperature of 550 °C without reducing the deposition rate too drastically, we learned that silicon fabricated by CVD is amorphous for substrate temperatures, Ts, of up to 670 °C. The improved thermal stability of the amorphous phase may be credited to the presence of hydrogen, incorporated into the film in amounts to less than 1 at. % depending upon Ts, due to the incomplete breakup of the silane molecule /6/. Although far below the hydrogen content characteristic for material deposited in an RF flow discharge, this fraction of 1 at. % of hydrogen effectively terminates dangling bonds. Electron spin resonance indicates spin densities in the order of 1019cm-3 in the CVD material /7/. The considerable thermal stability of CVD amorphous silicon promises satisfactory operation of the absorber over extended periods of time at 450 °C. Specific density, absorption coefficient, and refractive index were determined, the optical data confirming the superiority of amorphous over polycrystalline silicon as a solar absorber. Anneal at temperatures below the crystallization temperature Tc of 670 °C proved that CVD amorphous silicon, unlike material deposited by other methods, is anneal-stable /8/. The hypothesis that the retardation of the crystallization is caused by the presence of hydrogen stimulated a search for an even better stabilizer. Among the various elements introduced from the vapor phase into the growing film the most promise is shown by carbon /9/. Codeposition of 18 at. % carbon from acetylene gives a material that retains the solar absorptance of the non-intentionally doped amorphous silicon, but retards crystallization to 950 °C. Extrapolation on the basis of the crystallization kinetics predicts structural stability of this solar absorber over hundreds of years at 700 °C operating temperature

Differentially expressed genes regulating the progression of ductal carcinoma in situ to invasive breast cancer

Contains fulltext : 110917pub.pdf (publisher's version ) (Closed access)Molecular mechanisms mediating the progression of ductal carcinoma in situ (DCIS) to invasive breast cancer remain largely unknown. We used gene expression profiling of human DCIS (n = 53) and invasive breast cancer (n = 51) to discover uniquely expressed genes that may also regulate progression. There were 470 total differentially expressed genes (>/=2-fold; P /=2 studies (average 3.6 studies/gene; range 2-8 studies). Using hierarchical clustering, the 74-gene profile correctly categorized 96% of samples in this study and 94% of samples from 3 similar independent studies. To study the progression of DCIS to invasive breast cancer in vivo, we introduced human DCIS cell lines engineered to express specific genes into a "mammary intraductal DCIS" xenograft model. Progression of xenografts to invasive breast cancer was dramatically increased by suppressing four genes that were usually elevated in clinical samples of DCIS, including a protease inhibitor (CSTA) and genes involved in cell adhesion and signaling (FAT1, DST, and TMEM45A), strongly suggesting that they normally function to suppress progression. In summary, we have identified unique gene expression profiles of human DCIS and invasive breast cancer, which include novel genes regulating tumor progression. Targeting some of these genes may improve the detection, diagnosis, and therapy of DCIS