The Societal Influence of the NBA

Based on recent events, there has been a lot of discussion about the racial issues in America. Many professional athletes have been vocal about these issues, but NBA players seem to be at the forefront of many of the conversations regarding social injustice in this country. This article will examine different factors that have influenced the popularity of the National Basketball Association, such as product distribution, online engagement, global outreach, and the choice to allow players to use their platforms. The article will then argue how these factors have allowed the NBA and its players to be leaders in the fight for social justice. The acts of social activism carried out by the NBA will be analyzed through the lens of the ideology of Michelle Alexander and Ibram X. Kendi, who are both social activists and authors. The effectiveness of the NBA\u27s activism will also be discussed based on the reactions from the general public

Finite-Difference Modeling of the Batch Process Smoldering Combustion of Wastewater

A MATLAB model was developed for the smoldering combustion of wastewater in the context of a decentralized residential wastewater treatment appliance. Data from a batch process sewage smoldering experiment was simulated using implicit finite-difference approximations, assuming one-dimensional transient conductive heat transfer. The time-dependent temperature profiles within the column represented the main parameters of interest and were used to verify recoverable heat energy estimations. Given that the modeling method used for this thesis represents a unique approach, the assumptions and limitations of this model are thoroughly described in the context of reproducing results for other smoldering setups. A lack of convergence is seen in the model validation section of this report. Consequently, the practicality of this particular model contains significant limitations. Theoretical applications are also discussed and analyzed in terms of comparisons to modern alternatives and prototype feasibility

Gene therapy for lipid disorders

Lipid disorders are associated with atherosclerotic vascular disease, and therapy is associated with a substantial reduction in cardiovascular events. Current approaches to the treatment of lipid disorders are ineffective in a substantial number of patients. New therapies for refractory hypercholesterolemia, severe hypertriglyceridemia, and low levels of high-density lipoprotein cholesterol are needed: somatic gene therapy is one viable approach. The molecular etiology and pathophysiology of most of the candidate diseases are well understood. Animal models exist for the diseases and in many cases preclinical proof-of-principle studies have already been performed. There has been progress in the development of vectors that provide long-term gene expression. New clinical gene therapy trials for lipid disorders are likely to be initiated within the next few years

An orthotopic floor-of-mouth model for locoregional growth and spread of human squamous cell carcinoma

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74925/1/j.1600-0714.2007.00549.x.pd

Eribulin sensitizes oral squamous cell carcinoma cells to cetuximab via induction of mesenchymal-to-epithelial transition

Inhibition of epidermal growth factor receptor (EGFR) signalling has emerged as a new treatment strategy for oral squamous cell carcinoma (OSCC). Previously, we found that loss of EGFR expression in OSCC was associated with epithelial-mesenchymal transition (EMT), and may have functional implications with regard to resistance to cetuximab, a monoclonal anti-EGFR antibody. Eribulin (a microtubule inhibitor) reportedly renders breast cancer less aggressive, and less likely to metastasise, by triggering mesenchymal-to-epithelial (MET) transition. In the present study we evaluated whether eribulin-induced MET was associated with re-sensitization of resistant OSCC cell lines to cetuximab. In vitro antiproliferative activities were determined in three human OSCC lines (OSC-20, OSC-19 and HOC313) treated with eribulin. These three human OSCC represented different EMT/MET states. Interestingly, HOC313 cells (mesenchymal phenotype) were highly sensitive to eribulin in comparison with other cell lines, and significantly enhanced the anti-proliferative effect of cetuximab in response to the drug. Eribulin also underwent a MET-associated gene switch that resulted in morphological changes and high EGFR expression in HOC313 cells, and abrogated a TGF-β-induced EMT gene expression signature. Eribulin-dependent sensitization of OSCC to cetuximab is likely due to induction of MET. Combination therapies based on eribulin and cetuximab have potential as a novel treatment regimen in OSCC

Regulation of PD-L1 expression in a high-grade invasive human oral squamous cell carcinoma microenvironment

Blockade of the programmed-death 1 receptor (PD-1)/programmed-death ligand (PD-L1) pathway efficiently reduces tumour growth and improves survival. Durable tumour regression with blockade of the PD-1/PD-L1 checkpoint has been demonstrated in recent clinical studies. Oral squamous cell carcinoma (OSCC) is highly immunosuppressive, and PD-L1 expression has been proposed as a potential mechanism responsible for this phenotype. Despite the fact that anti-PD-1 treatment can produce durable responses, such therapy appears to benefit only a subset of patients. Thus, it is important to understand the mechanisms underlying regulation of PD-L1 expression in the OSCC microenvironment. In this study, we showed that PD-L1 expression in high-grade invasive OSCC cell lines was lower than that in a low-grade invasive OSCC line and found a close correlation between PD-L1 expression and the epithelial-mesenchymal transition (EMT). PD-L1 expression was upregulated in macrophages and dendritic cells (DCs) in high-grade invasive human OSCC tissues or co-cultured with mesenchymal-phenotype OSCC cells in vitro. TLR4-inhibitory peptide successfully suppressed PD-L1 upregulation on macrophages and DCs co-cultured with mesenchymal-phenotype OSCC cells, suggesting that some EMT-induced tumour antigen is critical for PD-L1 induction on tumour-associated macrophages and DCs. Further studies are necessary to explore the impact of EMT on the tumour immune microenvironment and to identify potential biomarkers for selecting patients who might preferentially benefit from PD-1/PD-L1 blockade or immunotherapies more broadly

口腔扁平上皮癌の化学療法剤による転移抑制効果に関する実験的研究

金沢大学医薬保健研究域医学系口腔扁平上皮癌の浸潤・転移に対する化学療法の効果を明らかにする目的で,高浸潤,高転移性質のヒト口腔扁平上皮癌細胞株であるOSC-19細胞をヌードマウスの口腔内に正所性に移植する浸潤・転移モデルを用いて実験的に検討した.第1実験としてOSC-19細胞を口底に移植した後に浸潤と転移が,一連に推移する状態において,シスプラチン(cisplatin,CDDP)または硫酸ペプロマイシン(peplomycin sulfate,PEP)を移植後7日目または14日目に腹腔内に単独投与し,各抗癌剤ならびに各投与時期の違いによる化学療法効果を比較検討した。その結果,対照群の口底腫瘍の増殖細胞核抗原(proliferating cell nuclear antigen,PCNA)陽性細胞率は33.7%であったのに対して,抗癌剤投与群では25.4-28.4%と有意に低下し(P<0.05),化学療法による増殖抑制効果が認められた.また,対照群の口底腫瘍は典型的な4C型の浸潤様式を呈していたが,抗癌剤投与群の残存腫瘍の浸潤様式は腫瘍胞巣の変性とともに3型にとどもまるものが72.7〜81.8%と多く抗癌剤投与によって浸潤様式の低下(down grading)といい得る所見が示された.さらに対象群の頚頭リンパ節転移形成率は90.9%であったのに対して抗癌剤の7日目投与群ではリンパ節転移形成率は45.5%と有意に低下し(p<0.05),また転移リンパ節内での腫瘍進展度も抑制されていた(p<0.01).第2実験ではOSC-19細胞を舌に移植し,その後に移植腫瘍を切除し転移のみが進行する状態において,移植腫瘍切除のみを施行するS単独群と術前化学療法を移植腫瘍切除に併用するC+S群の頚部リンパ節転移形成率の比較検討を行った.その結果,S単独群の頚リンパ節転移形成率は81.8%であったのに対して,C+S群の転移形成率は18.1%であり,腫瘍切除術に術前化学療法を併用することによって頚部リンパ節への転移が著しく抑制されていた(p<0.01)以上の結果より,移植腫瘍増殖初期で転移巣末形成期における化学療法が高浸潤,高転移性口腔扁平上波癌の浸潤・転移を抑制することが示された.研究課題/領域番号:09771749, 研究期間(年度):1997 – 1998出典：「口腔扁平上皮癌の化学療法剤による転移抑制効果に関する実験的研究」研究成果報告書　課題番号09771749（KAKEN：科学研究費助成事業データベース（国立情報学研究所））（https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-09771749/)を加工して作

口腔扁平上皮癌における抗癌剤および血管新生阻害剤の浸潤・転移に対する効果

口腔扁平上皮癌の浸潤と転移を臨床に近い状態で再現できる正所性移植モデルを用いて、特に日常の臨床で使用している抗癌剤に増殖のみならず、浸潤や転移に対する抑制効果があるのか否かを検討した。高浸潤高転移性のヒト口腔扁平上皮癌細胞株のOSC-19細胞をヌードマウスの口底もしくは舌に移植した後に、シスプラチンまたはペプロマイシンを移植後7日目または14日目に投与し、各抗癌剤ならびに各投与時期の違いによる腫瘍増殖に対する効果、浸潤に対する効果、転移に対する効果について検討した。増殖抑制効果では抗癌剤投与により平均38%の腫瘍縮小効果が認められ、PCNA陽性細胞率も有意に低下した。対照群の口底腫瘍は4C型の浸潤様式を呈していたが、抗癌剤投与群の浸潤様式は3型が72.7〜81.8%と多く、いわゆる浸潤様式の抗癌剤投与によるダウングレードが認められ、抗癌剤投与によって腫瘍の浸潤抑制効果が観察された。対照群の頚部リンパ節転移形成率は90.9%であったのに対して、抗癌剤の7日目投与群ではリンパ節転移形成率は45.5%と有意に低下し、また転移リンパ節内での腫瘍進展度も抑制されていた。すなわち抗癌剤投与により腫瘍の増殖のみならず浸潤や転移を抑制していた。また、血管新生阻害剤(TNP-470)を本モデルに同様に使用し、増殖、浸潤ならびに転移抑制効果の有無についても検討を行った。その結果では、増殖、浸潤、転移にそれぞれ一定以上の抑制効果が認められた。しかし、本剤においては特に局所腫瘍の増殖に対しての効果が大きく、それにつれて浸潤や転移の時期が遅くなっている印象であった。また、線維芽細胞増殖抑制剤(トラニラスト)を用いて同様の検討をした結果でも、増殖、浸潤、転移にそれぞれ抑制効果が認められた。Using an orthotopic Implantation model in which the invasion and metastasis of oral cancer can be reproduced, we investigated the inhibitory effects of anticancer agents on invasion and metastasis. A highly invasive and metastatic human oral squamous cell carcinoma cell line, OSC-19,was implanted into the oral floor of nude mice, and cisplatin or peplomycin was administered to the mice 7 or 14 days after the implantation. The effects of each anticancer drug and different administration timings on cancer invasion and metastasis were investigated. Tumor size and the ratio of proliferating cell nuclear antigen positive cells was significantly reduced. In the control group, the tumors showed grade 4C of mode of invasion, while in the groups treated with anticancer drugs, grade 3 was observed in 77.3% of the mice, with an inhibitory effect on tumor invasion being observed. The rate of metastasis in the cervical lymph node was significantly decreased in the groups treated with the cisplatin or peplomycin on day 7 after the implantation. The tumor stage progression in the metastatic lymph nodes was also inhibited. Chemotherapy is effective not only for tumor diminution, but also for inhibiting invasion and metastasis. The use of anticancer drugs considering these effects may be clinically very useful.研究課題/領域番号:16591989, 研究期間(年度):2004-2005出典：「口腔扁平上皮癌における抗癌剤および血管新生阻害剤の浸潤・転移に対する効果」研究成果報告書　課題番号16591989 (KAKEN：科学研究費助成事業データベース（国立情報学研究所）)　　　本文データは著者版報告書より作

L type Ca2+ channel blockers prevent oxaliplatin-induced cold hyperalgesia and TRPM8 overexpression in rats

<p>Abstract</p> <p>Background</p> <p>Oxaliplatin is an important drug used in the treatment of colorectal cancer. However, it frequently causes severe acute and chronic peripheral neuropathies. We recently reported that repeated administration of oxaliplatin induced cold hyperalgesia in the early phase and mechanical allodynia in the late phase in rats, and that oxalate derived from oxaliplatin is involved in the cold hyperalgesia. In the present study, we examined the effects of Ca²⁺channel blockers on oxaliplatin-induced cold hyperalgesia in rats.</p> <p>Methods</p> <p>Cold hyperalgesia was assessed by the acetone test. Oxaliplatin (4 mg/kg), sodium oxalate (1.3 mg/kg) or vehicle was injected i.p. on days 1 and 2. Ca²⁺(diltiazem, nifedipine and ethosuximide) and Na⁺(mexiletine) channel blockers were administered p.o. simultaneously with oxaliplatin or oxalate on days 1 and 2.</p> <p>Results</p> <p>Oxaliplatin (4 mg/kg) induced cold hyperalgesia and increased in the transient receptor potential melastatin 8 (TRPM8) mRNA levels in the dorsal root ganglia (DRG). Furthermore, oxalate (1.3 mg/kg) significantly induced the increase in TRPM8 protein in the DRG. Treatment with oxaliplatin and oxalate (500 μM for each) also increased the TRPM8 mRNA levels and induced Ca²⁺influx and nuclear factor of activated T-cell (NFAT) nuclear translocation in cultured DRG cells. These changes induced by oxalate were inhibited by nifedipine, diltiazem and mexiletine. Interestingly, co-administration with nifedipine, diltiazem or mexiletine prevented the oxaliplatin-induced cold hyperalgesia and increase in the TRPM8 mRNA levels in the DRG.</p> <p>Conclusions</p> <p>These data suggest that the L type Ca²⁺channels/NFAT/TRPM8 pathway is a downstream mediator for oxaliplatin-induced cold hyperalgesia, and that Ca²⁺channel blockers have prophylactic potential for acute neuropathy.</p