Radioenhancement with the Combination of Docetaxel and Ultrasound Microbubbles: In Vivo Prostate Cancer.

Using an in vitro prostate cancer model, we previously demonstrated the significant enhancement of radiotherapy (XRT) with the combined treatment of docetaxel (Taxotere; TXT) and ultrasound-microbubbles (USMB). Here, we extend these findings to an in vivo cancer model. Severe combined immune-deficient male mice were xenografted with the PC-3 prostate cancer cell line in the hind leg and treated with USMB, TXT, radiotherapy (XRT), and their combinations. The tumors were imaged with ultrasound pre-treatment and 24 h post-treatment, following which they were extracted for the histological analysis of the tumor-cell death (DN; H&E) and apoptosis (DA; TUNEL). The tumors' growths were assessed for up to ~6 weeks and analysed using the exponential Malthusian tumor-growth model. The tumors' doubling time (VT) was characterized as growth (positive) or shrinkage (negative). The cellular death and apoptosis increased ~5-fold with the TXT + USMB + XRT (Dn = 83% and Da = 71%) compared to the XRT alone (Dn = 16% and Da = 14%), and by ~2-3-fold with the TXT + XRT (Dn = 50% and Da = 38%) and USMB + XRT (Dn = 45% and Da = 27%) compared to the XRT. The USMB enhanced the cellular bioeffects of the TXT by ~2-5-fold with the TXT + USMB (Dn = 42% and Da = 50%), compared with the TXT alone (Dn = 19% and Da = 9%). The USMB alone caused cell death (Dn = 17% and Da = 10%) compared to the untreated control (Dn = 0.4% and Da = 0%). The histological cellular bioeffects were correlated with the changes in the ultrasound RF mid-band-fit data, which were associated with the cellular morphology. The linear regression analysis displayed a positive linear correlation between the mid-band fit and the overall cell death (R2 = 0.9164), as well as a positive linear correlation between the mid-band fit and the apoptosis (R2 = 0.8530). These results demonstrate a correlation between the histological and spectral measurements of the tissue microstructure and that cellular morphological changes can be detected by ultrasound scattering analysis. In addition, the tumor volumes from the triple-combination treatment were significantly smaller than those from the control, XRT, USMB + XRT, and TXT + XRT, from day 2 onward. The TXT + USMB + XRT-treated tumors shrank from day 2 and at each subsequent time-point measured (VT ~-6 days). The growth of the XRT-treated tumors was inhibited during the first 16 days, following which the tumors grew (VT ~9 days). The TXT + XRT and USMB + XRT groups displayed an initial decrease in tumor size (day 1-14; TXT + XRT VT ~-12 days; USMB + XRT VT ~-33 days), followed by a growth phase (day 15-37; TXT + XRT VT ~11 days; USMB + XRT VT ~22 days). The triple-combination therapy induced tumor shrinkage to a greater extent than any of the other treatments. This study demonstrates the in vivo radioenhancement potential of chemotherapy combined with therapeutic ultrasound-microbubble treatment in inducing cell death and apoptosis, as well as long-term tumor shrinkage.

Synergistic enhancement of cell death by triple combination therapy of docetaxel, ultrasound and microbubbles, and radiotherapy on PC3 a prostate cancer cell line.

The application of ultrasound and microbubbles (USMB) has been shown to enhance both chemotherapy and radiotherapy. This study investigated the potential of triple combination therapy comprised of USMB, docetaxel (Taxotere: TXT) chemotherapy and XRT to enhance treatment efficacy. Prostate cancer (PC3) cells in suspension were treated with various combinations of USMB, chemotherapy and radiotherapy. Cells were treated with ultrasound and microbubbles (500 kHz pulse center frequency, 580 kPa peak negative pressure, 10 µs pulse duration, 60 s insonation time and 2% Definity microbubbles (v/v)), XRT (2 Gy), and Taxotere (TXT) at concentrations ranging from 0.001 to 0.1 nM for 5- and 120-minutes duration. Following treatment, cell viability was assessed using a clonogenic assay. Therapeutic efficiency of the combined treatments depended on chemotherapy and microbubble exposure conditions. Under the exposure conditions of the study, the triple combination therapy synergistically enhanced clonogenic cell death compared to single and double combination therapy. Cell viability of ∼2% was achieved with the triple combination therapy corresponding to ∼29, ∼37, and ∼38 folds decrease compared to XRT (57%), USMB (74%) and TXT (76%) alone conditions, respectively. In addition, the triple combination therapy decreased cell viability by ∼29, ∼19- and ∼11 folds compared to TXT2hr + USMB (58%), TXT2hr + XRT (37%), and USMB + XRT (22%), respectively. The in vivo PC3 tumours showed that USMB significantly enhanced cell death through detection of apoptosis (TUNEL) with both TXT and TXT + XRT. The study demonstrated that the triple combination therapy can significantly enhance cell death in prostate cancer cells both in vitro and in vivo under relatively low chemotherapy and ionizing radiation doses.

Correction: Measuring attitudes towards biology major and non-major: Effect of students' gender, group composition, and learning environment.

[This corrects the article DOI: 10.1371/journal.pone.0251453.].

Simulations to Teach Science Subjects: Connections Among Students' Engagement, Self-Confidence, Satisfaction, and Learning Styles.

With the increasing technology integration practices in education, the adoption of computer simulations to teach conceptual understanding of science concepts is widely accepted by educators across the globe. To understand the connections between learners' engagement and satisfaction with simulations for science learning and their learning styles, the present study analyzed 1034 university students' perceptions and experiences of using simulations for learning physics, chemistry, and biology subjects. The study took place in a large public university in a gulf country. Precisely, this study provides an empirically driven exploration of the connection between tertiary students' engagement and satisfaction with simulation-based learning and their learning styles. The findings of this study showed that the participants showed a very high level of engagement and satisfaction with the use of simulations for learning science concepts in the subjects of physics, chemistry, and biology. Their self-confidence and VAK learning styles, particularly the kinesthetic style, were significant predictors of their engagement and satisfaction with the learning process. The findings from this study have implications for the benefit of researchers and practitioners interested in the effective adoption of computer simulations as a pedagogical approach in science education.

Measuring attitudes towards biology major and non-major: Effect of students' gender, group composition, and learning environment.

This study examined the effect of collaborative learning (CL) versus traditional lecture-based learning (TL) pedagogies and gender group composition in effecting positive or negative attitudes of biology major and nonmajor men and women students. The experimental research method was administered in experimental and control groups to test the hypotheses. Students' attitudes refer to their positive or negative feelings and inclinations to learn biology. A nine-factor attitude scale was administered in (1) single-gender nonmajor biology, (2) mixed-gender nonmajor biology, (3) single-gender major biology, and (4) mixed-gender biology major groups. Men (221) and women (219) were randomly assigned into single and mixed-gender classes without groups and single-gender groups (4M) or (4W) and mix-gender (2M+2W) groups. In CL nonmajor and major single-gender groups, women demonstrated significantly higher positive attitudes than men. In contrast, men's attitudes were significantly improved in mixed-gender CL groups for major and nonmajor sections, and the effect size was larger in mix-gender classes. Women feel less anxious in single-gender groups but more anxious in mixed-gender groups. In mixed-gender groups, men's self-efficacy, general interest, and motivation enhanced significantly; overall, men experienced greater satisfaction and triggered their desire to collaborate better, affecting all nine attitudinal factors. There was an interaction effect demonstrating the teaching pedagogy's impact on improving students' attitudes toward biology; students' gender and gender-specific group composition have been the most influential factor for nonmajor students. These findings suggest that there is a need for developing gender-specific and context-specific learning pedagogies, and instructors carefully select gender grouping in teaching undergraduate science subjects.