Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-2599
A. G. Theakstone, Paul M. Brennan, M. Baker
This study focuses on investigating the link between brain tumor volume and the spectroscopic classification between patients with known gliomas and healthy controls. Discrimination of brain cancer vs. non-cancer patients using serum-based ATR-FTIR diagnostics was first developed by Hands et al. achieving sensitivity and specificity values of 92.8% and 91.5% respectively. Cameron et al. then went on to stratifying between specific brain tumor types and was successful in providing a sensitivity of 90.1% and a specificity of 86.3%. Expanding on these studies, it is vital to determine if the size of a tumor has a direct effect on the sensitivity and specificity and whether or not it was only the larger tumors that were being identified as cancerous. A cohort of 90 patients whose tumor volumes were calculated using their MRI images (either T1-weighted contrast enhanced, T2-weighted or FLAIR images), including patients with high-grade glioblastoma multiforme (GBM), and low-grade gliomas such as anaplastic astrocytoma, astrocytoma, oligoastrocytoma and oligodendroglioma, were used for investigation. Utilizing ATR-FTIR spectroscopy coupled with machine learning algorithms these tumor patients were stratified against 87 healthy controls and were classified as either cancer or non-cancer. From these initial findings9 sensitivities, specificities and balanced accuracies were greater than 88% and cancer patients with tumor volumes as small as 0.2 cubic cm were correctly identified, demonstrating that classifications are not affected by tumor volume. Both small and low-grade gliomas were identified which shows great promise for this technique to be used as a screening tool or in diagnostics for early detection of brain tumors. Citation Format: Ashton G. Theakstone, Paul M. Brennan, Matthew J. Baker. Does tumor volume effect the spectroscopic classification of brain cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2599.
本研究的重点是研究已知胶质瘤患者和健康对照者之间脑肿瘤体积和光谱分类之间的联系。使用基于血清的ATR-FTIR诊断方法区分脑癌与非脑癌患者是由Hands等人首先开发的，其灵敏度和特异性分别为92.8%和91.5%。Cameron等人随后继续在特定脑肿瘤类型之间进行分层，并成功地提供了90.1%的敏感性和86.3%的特异性。在这些研究的基础上，至关重要的是要确定肿瘤的大小是否对敏感性和特异性有直接影响，以及是否只有较大的肿瘤才被确定为癌症。通过MRI图像(t1加权增强，t2加权或FLAIR图像)计算肿瘤体积的90例患者，包括高级别多形性胶质母细胞瘤(GBM)和低级别胶质瘤(如间变性星形细胞瘤，星形细胞瘤，少星形细胞瘤和少突胶质细胞瘤)患者，用于研究。利用ATR-FTIR光谱结合机器学习算法，将这些肿瘤患者与87名健康对照者进行分层，并将其分类为癌症或非癌症。从这些初步发现来看，敏感性、特异性和平衡准确性均大于88%，并且肿瘤体积小至0.2立方厘米的癌症患者也能被正确识别，这表明分类不受肿瘤体积的影响。小胶质瘤和低级别胶质瘤都被发现，这显示了这项技术作为筛查工具或早期发现脑肿瘤的诊断的巨大希望。引用格式:Ashton G. Theakstone, Paul M. Brennan, Matthew J. Baker。肿瘤体积是否影响脑癌患者的光谱分类?见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志，2021;81(13 -增刊):2599。
{"title":"Abstract 2599: Does tumor volume effect the spectroscopic classification of brain cancer patients","authors":"A. G. Theakstone, Paul M. Brennan, M. Baker","doi":"10.1158/1538-7445.AM2021-2599","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2599","url":null,"abstract":"This study focuses on investigating the link between brain tumor volume and the spectroscopic classification between patients with known gliomas and healthy controls. Discrimination of brain cancer vs. non-cancer patients using serum-based ATR-FTIR diagnostics was first developed by Hands et al. achieving sensitivity and specificity values of 92.8% and 91.5% respectively. Cameron et al. then went on to stratifying between specific brain tumor types and was successful in providing a sensitivity of 90.1% and a specificity of 86.3%. Expanding on these studies, it is vital to determine if the size of a tumor has a direct effect on the sensitivity and specificity and whether or not it was only the larger tumors that were being identified as cancerous. A cohort of 90 patients whose tumor volumes were calculated using their MRI images (either T1-weighted contrast enhanced, T2-weighted or FLAIR images), including patients with high-grade glioblastoma multiforme (GBM), and low-grade gliomas such as anaplastic astrocytoma, astrocytoma, oligoastrocytoma and oligodendroglioma, were used for investigation. Utilizing ATR-FTIR spectroscopy coupled with machine learning algorithms these tumor patients were stratified against 87 healthy controls and were classified as either cancer or non-cancer. From these initial findings9 sensitivities, specificities and balanced accuracies were greater than 88% and cancer patients with tumor volumes as small as 0.2 cubic cm were correctly identified, demonstrating that classifications are not affected by tumor volume. Both small and low-grade gliomas were identified which shows great promise for this technique to be used as a screening tool or in diagnostics for early detection of brain tumors. Citation Format: Ashton G. Theakstone, Paul M. Brennan, Matthew J. Baker. Does tumor volume effect the spectroscopic classification of brain cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2599.","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76359647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-2536
S. J. Rahman, Shilin Zhao, Shih-Kai Chu, Y. Zou, A. Hui, T. Stricker, Chen Heidi, M. Diehn, P. Massion
{"title":"Abstract 2536: Mutational landscape of the bronchial epithelium of individuals at high risk for lung cancer","authors":"S. J. Rahman, Shilin Zhao, Shih-Kai Chu, Y. Zou, A. Hui, T. Stricker, Chen Heidi, M. Diehn, P. Massion","doi":"10.1158/1538-7445.AM2021-2536","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2536","url":null,"abstract":"","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79871807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-LB224
A. Meirovitz, Daniela Nahmias, E. Hermano, O. Maimon, T. Peretz, M. Elkin
Obesity serves as a risk factor for estrogen-dependent postmenopausal breast cancer (BC). While the exact association occurring between these two disease states remains unknown, obesity-associated inflammation is thought to be the most likely contributing factor. In addition, obesity has been correlated to changes in gut microbiota composition and a subsequent chronic increase in bacterial endotoxin (lipopolysaccharide [LPS] - canonic ligand of toll-like receptor 4 [TLR4]) blood levels. It was recently shown that BC cells intrinsically express TLR4 and such expression has been associated with decreased patient survival as well as increased tumor growth. We hypothesized that obesity-associated endotoxemia may contribute to BC progression by utilizing TLR-dependent mechanisms and exerting cancer-promoting effects directly (on carcinoma cells) and indirectly (triggering abnormal activation of macrophages). Utilizing a chronic metabolic endotoxemia and breast cancer murine model as well as in vitro experimental systems, we found that continuous exposure to low concentrations of LPS not only promotes BC progression in vivo but stimulates BC cell growth in culture through the activation of key breast cancer-promoting signaling pathways (Stat3, Akt, ERK1/2). Obesity has reached epidemic proportions globally, where elucidation of the molecular mechanisms underlying breast tumor-promoting action of obesity has become of vital importance. Improving the understanding of such mechanisms has the potential to reveal improved efficacious therapy regimens and prevention strategies in a rapidly growing population of obese, breast cancer patients. Citation Format: Amichay Meirovitz, Daniela Nahmias, Esther Hermano, Ofra Maimon, Tamar Peretz, Michael Elkin. The potential effect of chronically increased endotoxin levels on breast carcinoma progression in obese patients. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB224.
{"title":"Abstract LB224: The potential effect of chronically increased endotoxin levels on breast carcinoma progression in obese patients.","authors":"A. Meirovitz, Daniela Nahmias, E. Hermano, O. Maimon, T. Peretz, M. Elkin","doi":"10.1158/1538-7445.AM2021-LB224","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-LB224","url":null,"abstract":"Obesity serves as a risk factor for estrogen-dependent postmenopausal breast cancer (BC). While the exact association occurring between these two disease states remains unknown, obesity-associated inflammation is thought to be the most likely contributing factor. In addition, obesity has been correlated to changes in gut microbiota composition and a subsequent chronic increase in bacterial endotoxin (lipopolysaccharide [LPS] - canonic ligand of toll-like receptor 4 [TLR4]) blood levels. It was recently shown that BC cells intrinsically express TLR4 and such expression has been associated with decreased patient survival as well as increased tumor growth. We hypothesized that obesity-associated endotoxemia may contribute to BC progression by utilizing TLR-dependent mechanisms and exerting cancer-promoting effects directly (on carcinoma cells) and indirectly (triggering abnormal activation of macrophages). Utilizing a chronic metabolic endotoxemia and breast cancer murine model as well as in vitro experimental systems, we found that continuous exposure to low concentrations of LPS not only promotes BC progression in vivo but stimulates BC cell growth in culture through the activation of key breast cancer-promoting signaling pathways (Stat3, Akt, ERK1/2). Obesity has reached epidemic proportions globally, where elucidation of the molecular mechanisms underlying breast tumor-promoting action of obesity has become of vital importance. Improving the understanding of such mechanisms has the potential to reveal improved efficacious therapy regimens and prevention strategies in a rapidly growing population of obese, breast cancer patients. Citation Format: Amichay Meirovitz, Daniela Nahmias, Esther Hermano, Ofra Maimon, Tamar Peretz, Michael Elkin. The potential effect of chronically increased endotoxin levels on breast carcinoma progression in obese patients. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB224.","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78672855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-2560
Alexandra M. Vaiana, Román A. Fernández, J. Gelfond, T. Johnson-Pais, R. Leach, C. Ramamurthy, I. Thompson, D. Morilak
{"title":"Abstract 2560: Plasticity-related signaling pathways in the medial prefrontal cortex and hippocampus as potential targets of the antidepressant vortioxetine in reversing cognitive impairments after androgen deprivation therapy for prostate cancer","authors":"Alexandra M. Vaiana, Román A. Fernández, J. Gelfond, T. Johnson-Pais, R. Leach, C. Ramamurthy, I. Thompson, D. Morilak","doi":"10.1158/1538-7445.AM2021-2560","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2560","url":null,"abstract":"","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73250300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-2580
L. Fan, D. Yu, Xiangzhu Zhu, Xuehong Zhang, Xiang Huang, H. Murff, M. Azcarate-Peril, M. Shrubsole, Q. Dai
The obesity epidemic has dramatically increased the type 2 diabetes (T2D) prevalence in the US over the past two decades. Previous studies have relatively consistently found individuals with T2D are at increased risks of cancer, including liver and colorectal cancer in which insulin resistance may play an important role. However, the mechanism remains largely unknown. Metformin, the primary first-line medication for the treatment of T2D, has been shown to improve insulin resistance and be linked to a reduced risk of hepatocellular carcinoma (HCC) and colorectal cancer (CRC). Two recent Cell and Cell metabolism publications identified that imidazole propionate (ImP), a microbial metabolite of histidine, significantly increased in patients with T2D and causally induced insulin resistance in mice. Furthermore, the therapeutic effects of metformin on insulin resistance disappeared when ImP was elevated, indicating that ImP plays a key role in developing insulin resistance and resistance to metformin treatment. Our recent work together with a subsequent study from others demonstrated higher magnesium (Mg) intake is associated with a substantially reduced risk of HCC, HCC mortality and mortality from liver diseases. Accumulative evidence, including our prior work, has also linked higher Mg intake to a reduced risk of colorectal neoplasia. Previous studies found that the process of the histidine utilization (Hut) system to metabolize histidine in some bacterial taxa depends on concentrations of divalent metal ion Mg2+. We hypothesize that low availability of Mg2+ in gut microbiota could terminate the Hut system and increase the production of intermediate metabolites, including ImP, over other end products. This will lead to increased levels of ImP in the gut and, in turn, liver and circulation. We tested our hypothesis in the Personalized Prevention of Colorectal Cancer Trial (PPCCT) (registered at clinicaltrials.gov as NCT01105169), a precision-based randomized trial enrolling 240 participants at high risk of Mg deficiency. Among 68 participants (34 treatment/34 placebo), we found that compared to the placebo, Mg treatment significantly reduced ImP by 39.9% compared to a 6.0% increase in the placebo arm after adjustment for baseline ImP (P=0.02). However, we found Mg treatment did not significantly affect the levels of trans-urocanate, the precursor of ImP. Since Mg deficiency leads to insulin resistance and as high as 50% of patients with T2D have hypomagnesemia, Mg deficiency may lead to an increased risk of ImP and, in turn, resistance to metformin which subsequently increases risk of HCC and CRC. Thus, futures studies should evaluate whether the joint use of Mg supplementation and metformin synergistically maximizes the efficacy of metformin and minimizes the treatment resistance on insulin resistance and, subsequently, prevention of HCC and CRC. Citation Format: Lei Fan, Danxia Yu, Xiangzhu Zhu, Xuehong Zhang, Xiang Huang, Harvey J. Murff, M. Andr
在过去的二十年里，肥胖的流行极大地增加了美国2型糖尿病(T2D)的患病率。先前的研究相对一致地发现，患有T2D的个体患癌症的风险增加，包括肝癌和结直肠癌，其中胰岛素抵抗可能起重要作用。然而，其机制在很大程度上仍然未知。二甲双胍是治疗T2D的主要一线药物，已被证明可以改善胰岛素抵抗，并与降低肝细胞癌(HCC)和结直肠癌(CRC)的风险有关。最近的两篇Cell和Cell metabolism出版物发现，组氨酸的微生物代谢物咪唑丙酸酯(ImP)在T2D患者中显著增加，并在小鼠中引起胰岛素抵抗。此外，当ImP升高时，二甲双胍对胰岛素抵抗的治疗作用消失，表明ImP在胰岛素抵抗和二甲双胍治疗抵抗中起关键作用。我们最近的工作和其他人随后的研究表明，较高的镁(Mg)摄入量与HCC风险、HCC死亡率和肝脏疾病死亡率的显著降低相关。累积的证据，包括我们之前的工作，也将较高的镁摄入量与降低结直肠肿瘤的风险联系起来。以往的研究发现，在某些细菌类群中，组氨酸利用(Hut)系统代谢组氨酸的过程取决于二价金属离子Mg2+的浓度。我们假设，肠道微生物群中Mg2+的低利用率可能会终止Hut系统，并增加中间代谢物(包括ImP)的产生，而不是其他最终产物。这将导致肠道内ImP水平的增加，进而导致肝脏和血液循环的增加。我们在个体化预防结直肠癌试验(PPCCT)(在clinicaltrials.gov注册为NCT01105169)中验证了我们的假设，这是一项基于精确的随机试验，招募了240名镁缺乏症高风险参与者。在68名参与者中(34名治疗组/34名安慰剂组)，我们发现与安慰剂组相比，Mg治疗组在调整基线ImP后显着降低了39.9%，而安慰剂组则增加了6.0% (P=0.02)。然而，我们发现Mg治疗并没有显著影响ImP的前体反式尿毒酸的水平。由于Mg缺乏导致胰岛素抵抗，高达50%的T2D患者有低镁血症，Mg缺乏可能导致ImP的风险增加，进而导致对二甲双胍的抵抗，从而增加HCC和CRC的风险。因此，未来的研究应该评估Mg补充剂和二甲双胍联合使用是否能协同最大化二甲双胍的疗效，最小化对胰岛素抵抗的治疗抵抗，从而预防HCC和CRC。引用格式:范磊，于丹霞，朱祥珠，张雪红，黄翔，Harvey J. Murff, M. Andrea Azcarate-Peril, Martha J. Shrubsole，戴琦。镁与二甲双胍预防肝癌和结直肠癌的协同作用[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志，2021;81(13 -增刊):2580。
{"title":"Abstract 2580: Synergistic effect of magnesium with metformin for the prevention of liver and colorectal cancer","authors":"L. Fan, D. Yu, Xiangzhu Zhu, Xuehong Zhang, Xiang Huang, H. Murff, M. Azcarate-Peril, M. Shrubsole, Q. Dai","doi":"10.1158/1538-7445.AM2021-2580","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2580","url":null,"abstract":"The obesity epidemic has dramatically increased the type 2 diabetes (T2D) prevalence in the US over the past two decades. Previous studies have relatively consistently found individuals with T2D are at increased risks of cancer, including liver and colorectal cancer in which insulin resistance may play an important role. However, the mechanism remains largely unknown. Metformin, the primary first-line medication for the treatment of T2D, has been shown to improve insulin resistance and be linked to a reduced risk of hepatocellular carcinoma (HCC) and colorectal cancer (CRC). Two recent Cell and Cell metabolism publications identified that imidazole propionate (ImP), a microbial metabolite of histidine, significantly increased in patients with T2D and causally induced insulin resistance in mice. Furthermore, the therapeutic effects of metformin on insulin resistance disappeared when ImP was elevated, indicating that ImP plays a key role in developing insulin resistance and resistance to metformin treatment. Our recent work together with a subsequent study from others demonstrated higher magnesium (Mg) intake is associated with a substantially reduced risk of HCC, HCC mortality and mortality from liver diseases. Accumulative evidence, including our prior work, has also linked higher Mg intake to a reduced risk of colorectal neoplasia. Previous studies found that the process of the histidine utilization (Hut) system to metabolize histidine in some bacterial taxa depends on concentrations of divalent metal ion Mg2+. We hypothesize that low availability of Mg2+ in gut microbiota could terminate the Hut system and increase the production of intermediate metabolites, including ImP, over other end products. This will lead to increased levels of ImP in the gut and, in turn, liver and circulation. We tested our hypothesis in the Personalized Prevention of Colorectal Cancer Trial (PPCCT) (registered at clinicaltrials.gov as NCT01105169), a precision-based randomized trial enrolling 240 participants at high risk of Mg deficiency. Among 68 participants (34 treatment/34 placebo), we found that compared to the placebo, Mg treatment significantly reduced ImP by 39.9% compared to a 6.0% increase in the placebo arm after adjustment for baseline ImP (P=0.02). However, we found Mg treatment did not significantly affect the levels of trans-urocanate, the precursor of ImP. Since Mg deficiency leads to insulin resistance and as high as 50% of patients with T2D have hypomagnesemia, Mg deficiency may lead to an increased risk of ImP and, in turn, resistance to metformin which subsequently increases risk of HCC and CRC. Thus, futures studies should evaluate whether the joint use of Mg supplementation and metformin synergistically maximizes the efficacy of metformin and minimizes the treatment resistance on insulin resistance and, subsequently, prevention of HCC and CRC. Citation Format: Lei Fan, Danxia Yu, Xiangzhu Zhu, Xuehong Zhang, Xiang Huang, Harvey J. Murff, M. Andr","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73836402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-2594
E. Shankar, Albert S Lee, Rajnee Kanwal, Sanjay Gupta
Loss of tumor suppressors leads to acquisition of metastatic capability during prostate cancer progression leading to higher mortality. Maspin (SERPINB5) is a unique member of the serpin (serine protease inhibitor) family shown to regulate cell motility, migration and invasiveness. Loss of maspin is frequently identified in clinical prostate cancer specimens and prostate cancer cell lines, therefore novel therapeutic approaches to restore its expression are needed. We recently demonstrated that knockdown of class I HDACs increase maspin expression in prostate cancer cells [Mol Carcinog. 59(8):955-966, 2020]. Apigenin (49, 5, 7-trihydroxyflavone), a plant flavone has shown to possess anticancer properties and alters pathways that regulate tumor cell invasion and metastasis, however, the molecular basis of these effects remains unclear. We investigated whether apigenin has ability to restore maspin expression and contribute to the inhibition of metastasis. Treatment of human prostate cancer LNCaP and 22Rv1 cells, both harboring wild type p53, with 1-40 µM apigenin for 72 h resulted in a dose- and time- dependent decrease in cell invasion and migration with concurrent increase in maspin expression in the nuclear compartment. Since, p53 activates maspin promoter by binding directly to p53 consensus-binding site, we studied the effect of apigenin in potentially restoring p53-mediated maspin levels. Exposure of LNCaP and 22Rv1 cells with 5-20 μM of apigenin resulted in dose-dependent increase in maspin expression and p53 activation through acetylation at the Lys305 residue. These effects were associated with the inhibition of class I HDAC levels. Furthermore, apigenin withdrawal resulted in the loss of maspin expression and p53 acetylation in LNCaP cells. The increased apigenin-mediated p53 acetylation enhanced its binding on maspin promoter, which was associated with decrease in cell invasion and migration. Apigenin treatment also caused accumulation of acetylated histone H3 in total cellular chromatin, increasing accessibility to bind with the promoter sequences of maspin, consistent with the effects elicited by HDAC inhibitor, Tricostatin A. Similar observations of inhibition of class I HDACs and increase in p53 transcriptional activity were noted after feeding apigenin at 20- and 50- µg/day to 22Rv1 tumor xenograft implanted in athymic nude mice. Our results demonstrate that apigenin-mediated increase in maspin expression together with downregulation of class I HDACs, increases p53 activation resulting in decreased invasiveness and migration capabilities in prostate cancer. Citation Format: Eswar Shankar, Albert Lee, Rajnee Kanwal, Sanjay Gupta. Reactivation of maspin by plant flavone apigenin through inhibition of class I HDACs and increase in p53 transcriptional activity in prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; C
{"title":"Abstract 2594: Reactivation of maspin by plant flavone apigenin through inhibition of class I HDACs and increase in p53 transcriptional activity in prostate cancer cells","authors":"E. Shankar, Albert S Lee, Rajnee Kanwal, Sanjay Gupta","doi":"10.1158/1538-7445.AM2021-2594","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2594","url":null,"abstract":"Loss of tumor suppressors leads to acquisition of metastatic capability during prostate cancer progression leading to higher mortality. Maspin (SERPINB5) is a unique member of the serpin (serine protease inhibitor) family shown to regulate cell motility, migration and invasiveness. Loss of maspin is frequently identified in clinical prostate cancer specimens and prostate cancer cell lines, therefore novel therapeutic approaches to restore its expression are needed. We recently demonstrated that knockdown of class I HDACs increase maspin expression in prostate cancer cells [Mol Carcinog. 59(8):955-966, 2020]. Apigenin (49, 5, 7-trihydroxyflavone), a plant flavone has shown to possess anticancer properties and alters pathways that regulate tumor cell invasion and metastasis, however, the molecular basis of these effects remains unclear. We investigated whether apigenin has ability to restore maspin expression and contribute to the inhibition of metastasis. Treatment of human prostate cancer LNCaP and 22Rv1 cells, both harboring wild type p53, with 1-40 µM apigenin for 72 h resulted in a dose- and time- dependent decrease in cell invasion and migration with concurrent increase in maspin expression in the nuclear compartment. Since, p53 activates maspin promoter by binding directly to p53 consensus-binding site, we studied the effect of apigenin in potentially restoring p53-mediated maspin levels. Exposure of LNCaP and 22Rv1 cells with 5-20 μM of apigenin resulted in dose-dependent increase in maspin expression and p53 activation through acetylation at the Lys305 residue. These effects were associated with the inhibition of class I HDAC levels. Furthermore, apigenin withdrawal resulted in the loss of maspin expression and p53 acetylation in LNCaP cells. The increased apigenin-mediated p53 acetylation enhanced its binding on maspin promoter, which was associated with decrease in cell invasion and migration. Apigenin treatment also caused accumulation of acetylated histone H3 in total cellular chromatin, increasing accessibility to bind with the promoter sequences of maspin, consistent with the effects elicited by HDAC inhibitor, Tricostatin A. Similar observations of inhibition of class I HDACs and increase in p53 transcriptional activity were noted after feeding apigenin at 20- and 50- µg/day to 22Rv1 tumor xenograft implanted in athymic nude mice. Our results demonstrate that apigenin-mediated increase in maspin expression together with downregulation of class I HDACs, increases p53 activation resulting in decreased invasiveness and migration capabilities in prostate cancer. Citation Format: Eswar Shankar, Albert Lee, Rajnee Kanwal, Sanjay Gupta. Reactivation of maspin by plant flavone apigenin through inhibition of class I HDACs and increase in p53 transcriptional activity in prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; C","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77305898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-2607
Monica Saravana Vela, J. Berei, Katrina Dovalovsky, S. Sreenivasappa, J. Ross, Luigi Moruzzi, S. Martell, W. Schulz, N. Puri
Background: Lung cancer is the leading cause of cancer-related deaths in the United States. In 2019, 23.5% of deaths from cancer in the United States were attributed to lung cancer, a greater proportion than those from breast, prostate, pancreatic, and ovarian cancers combined. Lung cancer9s high mortality rate is largely due to the fact that approximately 75% of new cases are diagnosed in late stages. On a local level, Winnebago County has 17% higher incidence and mortality rates due to lung cancer than the corresponding national rates. Low-dose computed tomography (LDCT) is a valuable lung screening technique that utilizes 90% less ionizing radiation than a conventional chest CT scan. Hypothesis/Aims: Increased awareness of LDCT in clinical and community settings will lead to increased detection of lung cancer in early stages and decreased mortality. Study Design: We spread information on the new U.S. Preventive Services Task Force guidelines to both smokers and physicians in Winnebago County. We evaluated the number of LDCT screenings in Winnebago County between June 2015-March 2019, and recorded the number and stage classifications of lung cancer cases detected after these screenings. We also surveyed physicians and smokers on their likelihood of recommending LDCT to others after our seminars. Lastly, we created a Facebook page (Northern Illinois Lung Cancer Screening Project) to continue promoting LDCT screening in a socially distanced manner. Results: 15 seminars and 37 public awareness booths targeting an estimated 300 physicians and 1,450 smokers were conducted to increase knowledge of LDCT. 2,076 patients underwent LDCT screening at local hospitals. 28 patients were diagnosed with lung cancer, with 17 cases being early stage. 1,000 additional individuals were found to have small lung nodules. According to our surveys, 100% of attendees felt motivated to tell others about LDCT screening after attending our seminars. These studies are also being extended to Boone, Ogle, and Stephenson Counties, which have high incidence of mortality rates attributed to lung cancer. In an alternative effort to promote lung cancer screening in Northern Illinois, we created a Facebook page where we publish posts weekly and have reached over 1109 people and garnered 142 engagements from users. Conclusions: 17 local community members were diagnosed with early stage lung cancer, thus improving their prognosis and increasing therapy options. These community-based studies are being expanded to surrounding areas to expand the reach and effectiveness of our studies. Citation Format: Monica Saravana Vela, Joseph Berei, Katrina Dovalovsky, Shylendra Sreenivasappa, Joseph Ross, Luigi Moruzzi, Sandra Martell, William Schulz, Neelu Puri. Promotion of low-dose computed tomography for early-stage lung cancer detection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cance
背景:肺癌是美国癌症相关死亡的主要原因。2019年，美国23.5%的癌症死亡归因于肺癌，这一比例高于乳腺癌、前列腺癌、胰腺癌和卵巢癌的总和。肺癌的高死亡率主要是由于大约75%的新病例是在晚期被诊断出来的。在地方一级，温尼贝戈县的肺癌发病率和死亡率比全国相应的发病率和死亡率高17%。低剂量计算机断层扫描(LDCT)是一种有价值的肺部筛查技术，比传统的胸部CT扫描使用的电离辐射少90%。假设/目的:在临床和社区环境中提高对LDCT的认识将导致肺癌早期检测的增加和死亡率的降低。研究设计:我们向Winnebago县的吸烟者和医生传播新的美国预防服务工作组指南的信息。我们评估了2015年6月至2019年3月期间温尼贝戈县LDCT筛查的数量，并记录了筛查后发现的肺癌病例的数量和分期分类。我们还调查了医生和吸烟者在研讨会结束后向他人推荐LDCT的可能性。最后，我们创建了一个Facebook页面(北伊利诺斯州肺癌筛查项目)，继续以社会隔离的方式推广LDCT筛查。结果:举办了15场研讨会和37个公众宣传摊位，目标是约300名医生和1,450名吸烟者，以提高LDCT的知识。2076名患者在当地医院接受了LDCT筛查。28例患者确诊为肺癌，其中早期17例。另有1000人被发现有小肺结节。根据我们的调查，100%的与会者在参加完我们的研讨会后都有动力告诉别人LDCT筛查。这些研究也被扩展到布恩、奥格尔和斯蒂芬森县，这些县的肺癌死亡率很高。为了在北伊利诺斯州推广肺癌筛查，我们创建了一个Facebook页面，每周发布帖子，已经有超过1109人参与，获得了142个用户的参与。结论:17名当地社区成员被诊断为早期肺癌，从而改善了他们的预后，增加了治疗选择。这些以社区为基础的研究正在扩大到周边地区，以扩大我们研究的范围和有效性。引文格式:Monica Saravana Vela, Joseph Berei, Katrina Dovalovsky, Shylendra Sreenivasappa, Joseph Ross, Luigi Moruzzi, Sandra Martell, William Schulz, Neelu Puri。低剂量ct在早期肺癌检测中的推广应用[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志，2021;81(13 -增刊):2607。
{"title":"Abstract 2607: Promotion of low-dose computed tomography for early-stage lung cancer detection","authors":"Monica Saravana Vela, J. Berei, Katrina Dovalovsky, S. Sreenivasappa, J. Ross, Luigi Moruzzi, S. Martell, W. Schulz, N. Puri","doi":"10.1158/1538-7445.AM2021-2607","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2607","url":null,"abstract":"Background: Lung cancer is the leading cause of cancer-related deaths in the United States. In 2019, 23.5% of deaths from cancer in the United States were attributed to lung cancer, a greater proportion than those from breast, prostate, pancreatic, and ovarian cancers combined. Lung cancer9s high mortality rate is largely due to the fact that approximately 75% of new cases are diagnosed in late stages. On a local level, Winnebago County has 17% higher incidence and mortality rates due to lung cancer than the corresponding national rates. Low-dose computed tomography (LDCT) is a valuable lung screening technique that utilizes 90% less ionizing radiation than a conventional chest CT scan. Hypothesis/Aims: Increased awareness of LDCT in clinical and community settings will lead to increased detection of lung cancer in early stages and decreased mortality. Study Design: We spread information on the new U.S. Preventive Services Task Force guidelines to both smokers and physicians in Winnebago County. We evaluated the number of LDCT screenings in Winnebago County between June 2015-March 2019, and recorded the number and stage classifications of lung cancer cases detected after these screenings. We also surveyed physicians and smokers on their likelihood of recommending LDCT to others after our seminars. Lastly, we created a Facebook page (Northern Illinois Lung Cancer Screening Project) to continue promoting LDCT screening in a socially distanced manner. Results: 15 seminars and 37 public awareness booths targeting an estimated 300 physicians and 1,450 smokers were conducted to increase knowledge of LDCT. 2,076 patients underwent LDCT screening at local hospitals. 28 patients were diagnosed with lung cancer, with 17 cases being early stage. 1,000 additional individuals were found to have small lung nodules. According to our surveys, 100% of attendees felt motivated to tell others about LDCT screening after attending our seminars. These studies are also being extended to Boone, Ogle, and Stephenson Counties, which have high incidence of mortality rates attributed to lung cancer. In an alternative effort to promote lung cancer screening in Northern Illinois, we created a Facebook page where we publish posts weekly and have reached over 1109 people and garnered 142 engagements from users. Conclusions: 17 local community members were diagnosed with early stage lung cancer, thus improving their prognosis and increasing therapy options. These community-based studies are being expanded to surrounding areas to expand the reach and effectiveness of our studies. Citation Format: Monica Saravana Vela, Joseph Berei, Katrina Dovalovsky, Shylendra Sreenivasappa, Joseph Ross, Luigi Moruzzi, Sandra Martell, William Schulz, Neelu Puri. Promotion of low-dose computed tomography for early-stage lung cancer detection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cance","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77575534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-2525
D. J. Craig, E. Crawford, P. Massion, Thomas Morrison, J. Willey
{"title":"Abstract 2525: Low frequency TP53 mutations in airway epithelial cells serve as lung cancer risk biomarker","authors":"D. J. Craig, E. Crawford, P. Massion, Thomas Morrison, J. Willey","doi":"10.1158/1538-7445.AM2021-2525","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2525","url":null,"abstract":"","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72961864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-2540
Marjorie Petty
{"title":"Abstract 2540: Belief in research, religious coping, and willingness to participate in clinical trials among African Americans with hematologic malignancies: a pilot study","authors":"Marjorie Petty","doi":"10.1158/1538-7445.AM2021-2540","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2540","url":null,"abstract":"","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72993471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：