Evolving Patterns of Metastasis in Renal Cell Carcinoma: Do We Need to Perform Routine Bone Imaging?

Advance diagnostic and treatment modalities have improved outcomes for renal cell carcinoma (RCC) patients, but the prognosis for those with metastatic disease (mRCC) remains poor. As given metastatic distribution is critical in guiding treatment decisions for mRCC patients, we evaluated evolving metastatic patterns to assess if our current practice standards effectively address patient needs. A systematic literature review was performed to identify all publicly available prospective clinical trials in metastatic renal cell carcinoma (mRCC) from 1990 to 2018. A total of 16,899 mRCC patients from 127 qualified phase I–III clinical trials with metastatic site documentations were included for analysis for incidence of metastases to lung, liver, bone, and lymph nodes (LNs) over time. Studies were categorized into three treatment eras based on the timing of regulatory approval: Cytokine Era (1990-2004), vascular endothelial growth factor/tyrosine kinase inhibitor (TKI) Era (2005-2016), and immune checkpoint inhibitor/TKI Era (ICI-TKI, 2017-2018) and also classified as first-line only (FLO) or second-line and beyond (SLB). Overall, an increase in the incidence of bone and LNs metastases in FLO and SLB, and lung metastases in FLO, was seen over the three treatment eras. Generally, the burden of disease is higher in SLB when compared with FLO. Importantly, in the ICI-TKI era, the incidences of bone metastasis are 28% in FLO and 29% in SLB settings. The disease burden in patients with mRCC has increased steadily over the past three decades. Given the unexpectedly high rate of bone metastasis, routine dedicated bone imaging should be considered in all patients with mRCC

Multi-Segment Foam Flow Field in Ambient Pressure Polymer Exchange Membrane Fuel Cell

In order to produce low-cost flow field plates for polymer electrolyte membrane fuel cells, we used nickel foam in this study rather than conventional flow field. Nickel foam has high electron conductivity, thermal conductivity, and mechanical strength. Electrochemical impedance spectrum analysis is carried out to evidence the use on flow field plates of nickel foam. From the impedance fitting results, the nickel foam cases showed the lower contact resistance than the serpentine. However, such plates have poor performance at low temperatures and ambient pressure. In order to overcome this, a multi-segment foam flow field is designed in this study. This increased the performance of the polarization curve by 70% from 162 to 275.5 mw cm-2 than the original nickel foam design. Also, the mass transfer resistance was reduced, and the Warburg impedance value of the operation voltage decreased by 0.4 V. The numerical analysis results demonstrate that increased segment numbers can increase the performance of the multi-segment foam flow field

Static Magnetic Field Attenuates Lipopolysaccharide-Induced Inflammation in Pulp Cells by Affecting Cell Membrane Stability

One of the causes of dental pulpitis is lipopolysaccharide- (LPS-) induced inflammatory response. Following pulp tissue inflammation, odontoblasts, dental pulp cells (DPCs), and dental pulp stem cells (DPSCs) will activate and repair damaged tissue to maintain homeostasis. However, when LPS infection is too serious, dental repair is impossible and disease may progress to irreversible pulpitis. Therefore, the aim of this study was to examine whether static magnetic field (SMF) can attenuate inflammatory response of dental pulp cells challenged with LPS. In methodology, dental pulp cells were isolated from extracted teeth. The population of DPSCs in the cultured DPCs was identified by phenotypes and multilineage differentiation. The effects of 0.4 T SMF on DPCs were observed through MTT assay and fluorescent anisotropy assay. Our results showed that the SMF exposure had no effect on surface markers or multilineage differentiation capability. However, SMF exposure increases cell viability by 15%. In addition, SMF increased cell membrane rigidity which is directly related to higher fluorescent anisotropy. In the LPS-challenged condition, DPCs treated with SMF demonstrated a higher tolerance to LPS-induced inflammatory response when compared to untreated controls. According to these results, we suggest that 0.4 T SMF attenuates LPS-induced inflammatory response to DPCs by changing cell membrane stability

Randomized, Noncomparative, Phase II Trial of Early Switch From Docetaxel to Cabazitaxel or Vice Versa, With Integrated Biomarker Analysis, in Men With Chemotherapy-Naïve, Metastatic, Castration-Resistant Prostate Cancer

Purpose The TAXYNERGY trial ( ClinicalTrials.gov identifier: NCT01718353) evaluated clinical benefit from early taxane switch and circulating tumor cell (CTC) biomarkers to interrogate mechanisms of sensitivity or resistance to taxanes in men with chemotherapy-naïve, metastatic, castration-resistant prostate cancer. Patients and Methods Patients were randomly assigned 2:1 to docetaxel or cabazitaxel. Men who did not achieve ≥ 30% prostate-specific antigen (PSA) decline by cycle 4 (C4) switched taxane. The primary clinical endpoint was confirmed ≥ 50% PSA decline versus historical control (TAX327). The primary biomarker endpoint was analysis of post-treatment CTCs to confirm the hypothesis that clinical response was associated with taxane drug-target engagement, evidenced by decreased percent androgen receptor nuclear localization (%ARNL) and increased microtubule bundling. Results Sixty-three patients were randomly assigned to docetaxel (n = 41) or cabazitaxel (n = 22); 44.4% received prior potent androgen receptor-targeted therapy. Overall, 35 patients (55.6%) had confirmed ≥ 50% PSA responses, exceeding the historical control rate of 45.4% (TAX327). Of 61 treated patients, 33 (54.1%) had ≥ 30% PSA declines by C4 and did not switch taxane, 15 patients (24.6%) who did not achieve ≥ 30% PSA declines by C4 switched taxane, and 13 patients (21.3%) discontinued therapy before or at C4. Of patients switching taxane, 46.7% subsequently achieved ≥ 50% PSA decrease. In 26 CTC-evaluable patients, taxane-induced decrease in %ARNL (cycle 1 day 1 v cycle 1 day 8) was associated with a higher rate of ≥ 50% PSA decrease at C4 ( P = .009). Median composite progression-free survival was 9.1 months (95% CI, 4.9 to 11.7 months); median overall survival was not reached at 14 months. Common grade 3 or 4 adverse events included fatigue (13.1%) and febrile neutropenia (11.5%). Conclusion The early taxane switch strategy was associated with improved PSA response rates versus TAX327. Taxane-induced shifts in %ARNL may serve as an early biomarker of clinical benefit in patients treated with taxanes

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.Peer reviewe

Synthesis, Properties and Applications of Novel Bacteriochlorin Photo-sensitizers

[[abstract]]在這裡我們研究具有空氣穩定性及 meso 位取代的菌綠素 LS-17、LS-20　與 LS-21。使用 copper-free Sonogashira cross-coupling 的方法合成出這些菌綠素化合物，並且研究探討這些菌綠素的光譜學以及電化學性質。LS-17 與 LS-21的性質會和先前我們實驗室發表過的 LS-01 與 LS-11 進行比較。 在 LS-11 與 LS-17 的部分，LS-17 和 LS-11 具有相似的吸收光譜與螢光光譜，但是 LS-17 的螢光量子產率較小。 而在 LS-01 與 LS-21 的部分，兩支菌綠素染料吸附於二氧化鈦奈米粒子上，會產生分子堆疊的情形。經由紫外-可見光吸收光譜測量，可以觀察到 LS-21 菌綠素染料分子結構上增加立體障礙，可以有效抑制染料堆疊的現象發生。[[abstract]]In this study, we report the properties and the applications of air stable, meso-substituted bacteriochlorins, LS-17, LS-20 and LS-21. They are successfully synthesized by using copper-free Sonogashira cross-coupling method and their UV-Visible absorption and redox are studied. The properties of LS-17 and LS-21 are compared to the results of previous studies, LS-01 and LS-11. For LS-11 and LS-17, the UV-Visible absoption spectra and fluorescence spectra of LS-17 and LS-11 is similar but LS-17 have more lower quantum yield. For LS-01 and LS-21, the UV-Visible absoption spectra of LS-01 on TiO2 films show that the Soret bands shift is bathochromic and Q band shift slightly and broaden by J-type aggregation and H-type aggregation. In case of LS-21 have 3,5-di-tert-butyl-phenyl side groups on bacteriochlorin ring, it effectively lessons dye aggregation of the bacteriochlorins on TiO2 surfaces.[[note]]碩

The role of cabazitaxel in the treatment of metastatic castration-resistant prostate cancer

For decades, cytotoxic therapy was considered ineffective for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Earlier therapies such as estramustine and mitoxantrone received regulatory approval based upon improvement in palliative endpoints. In 2004, docetaxel became the first treatment to demonstrate a significant survival benefit in patients with mCRPC based on two randomized phase III studies, TAX327 and SWOG 99-16. Cabazitaxel, a third-generation taxane, was chosen for clinical development based on its decreased affinity for the drug efflux pump, p-glycoprotein, which is a frequent cause of drug resistance in docetaxel-resistant preclinical models. In 2010, cabazitaxel was approved by the US Food and Drug Administration as the first therapy to show a survival benefit for the treatment of patients with docetaxel-refractory mCRPC. This review summarizes the existing literature on the use of cabazitaxel, focusing on its efficacy and safety in combination with prednisone in the treatment of mCRPC, as well as its role in an era of new therapeutic options

Clinical Development of Cabazitaxel for the Treatment of Castration-Resistant Prostate Cancer

Castration resistant prostate cancer has historically been considered chemotherapy insensitive. However, the approval of estramustine phosphate, mitoxantrone, and docetaxel, over the past few decades, has challenged this notion. Despite these advances, until recently, only docetaxel had been shown to improve survival in patients with castration-resistant disease, and there has been no standard treatment options available for men with disease progression on docetaxel. In the last year, cabazitaxel, a novel taxane with decreased affinity for ATP-dependent drug efflux pump P-glycoprotein, became the first cytotoxic agent to demonstrate an improvement in survival in men with docetaxel-refractory disease, and has received regulatory approval for treatment in this setting. In this review, we examine the clinical development of cabazitaxel for the treatment of castration-resistant prostate cancer, as well as rationale and direction of future therapeutic investigation

Moving beyond vascular endothelial growth factor-targeted therapy in renal cell cancer: latest evidence and therapeutic implications

Renal cell cancer (RCC) continues to be among the most lethal malignancies in the USA. Introduction of anti-vascular epidermal growth factor receptor tyrosine kinase inhibitors over a decade ago resulted in improvement in disease outcomes, but further development of new therapies largely stagnated for many years. More recently, a better understanding of disease biology and treatment-resistance patterns has led to a second renaissance in drug development, with the anti-programmed cell death protein 1 immune checkpoint inhibitor, nivolumab, paving the way for additional therapies entering clinical trial testing in the treatment of RCC