Oncoscience最新文献_第4页

VTT-006, an anti-mitotic compound, binds to the Ndc80 complex and suppresses cancer cell growth in vitro. VTT-006是一种抗有丝分裂化合物，与Ndc80复合物结合并在体外抑制癌细胞生长。

Oncoscience Pub Date : 2021-12-10 eCollection Date: 2021-01-01 DOI: 10.18632/oncoscience.549

Leena J Laine, Jenni H E Mäki-Jouppila, Emma Kutvonen, Pekka Tiikkainen, Thomas K M Nyholm, Jerry F Tien, Neil T Umbreit, Ville Härmä, Lila Kallio, Trisha N Davis, Charles L Asbury, Antti Poso, Gary J Gorbsky, Marko J Kallio

{"title":"VTT-006, an anti-mitotic compound, binds to the Ndc80 complex and suppresses cancer cell growth in vitro.","authors":"Leena J Laine, Jenni H E Mäki-Jouppila, Emma Kutvonen, Pekka Tiikkainen, Thomas K M Nyholm, Jerry F Tien, Neil T Umbreit, Ville Härmä, Lila Kallio, Trisha N Davis, Charles L Asbury, Antti Poso, Gary J Gorbsky, Marko J Kallio","doi":"10.18632/oncoscience.549","DOIUrl":"https://doi.org/10.18632/oncoscience.549","url":null,"abstract":"Hec1 (Highly expressed in cancer 1) resides in the outer kinetochore where it works to facilitate proper kinetochore-microtubule interactions during mitosis. Hec1 is overexpressed in various cancers and its expression shows correlation with high tumour grade and poor patient prognosis. Chemical perturbation of Hec1 is anticipated to impair kinetochore-microtubule binding, activate the spindle assembly checkpoint (spindle checkpoint) and thereby suppress cell proliferation. In this study, we performed high-throughput screen to identify novel small molecules that target the Hec1 calponin homology domain (CHD), which is needed for normal microtubule attachments. 4 million compounds were first virtually fitted against the CHD, and the best hit molecules were evaluated in vitro. These approaches led to the identification of VTT-006, a 1,2-disubstituted-tetrahydro-beta-carboline derivative, which showed binding to recombinant Ndc80 complex and modulated Hec1 association with microtubules in vitro. VTT-006 treatment resulted in chromosome congression defects, reduced chromosome oscillations and induced loss of inter-kinetochore tension. Cells remained arrested in mitosis with an active spindle checkpoint for several hours before undergoing cell death. VTT-006 suppressed the growth of several cancer cell lines and enhanced the sensitivity of HeLa cells to Taxol. Our findings propose that VTT-006 is a potential anti-mitotic compound that disrupts M phase, impairs kinetochore-microtubule interactions, and activates the spindle checkpoint.","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8667816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39852982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Berry anthocyanidins inhibit intestinal polyps and colon tumors by modulation of Src, EGFR and the colon inflammatory environment. 浆果花青素通过调节Src、EGFR和结肠炎症环境抑制肠息肉和结肠肿瘤。

Oncoscience Pub Date : 2021-12-10 eCollection Date: 2021-01-01 DOI: 10.18632/oncoscience.548

Ashley M Mudd, Tao Gu, Radha Munagala, Jeyaprakash Jeyabalan, Mostafa Fraig, Nejat K Egilmez, Ramesh C Gupta

{"title":"Berry anthocyanidins inhibit intestinal polyps and colon tumors by modulation of Src, EGFR and the colon inflammatory environment.","authors":"Ashley M Mudd, Tao Gu, Radha Munagala, Jeyaprakash Jeyabalan, Mostafa Fraig, Nejat K Egilmez, Ramesh C Gupta","doi":"10.18632/oncoscience.548","DOIUrl":"https://doi.org/10.18632/oncoscience.548","url":null,"abstract":"Colorectal cancer is the third most common form of cancer diagnosed and the third leading class for cancer-related deaths. Given the prevalence of colon cancer worldwide, further insight into developing novel and effective prevention and treatment strategies are warranted. The family of plant pigments known as the anthocyanins has been identified with a variety of health benefits including chemopreventive and therapeutic effects. A limitation to current clinical applications of anthocyanins is the high doses that are required. In order to overcome this limitation, we tested the active moiety, anthocyanidins for chemopreventive and therapeutic effects against colorectal cancer in vivo and in vitro. Treatment with native anthocyanidin mixture (Anthos) from bilberry yielded significant antiproliferative activity against colon cancer cells. Anthos treatment led to significant reductions in polyp and tumor counts in vivo. Reduced Src and EGFR phosphorylation was observed with Anthos treatment, which correlated with downstream targets such as PD-L1 and modulation of the colon inflammatory environment. These results provide a promising outlook on the impact of berry Anthos for the treatment and prevention of familial adenomatous polyposis and colorectal cancer. Results from this study also provide novel mechanistic insight into the chemopreventive and therapeutic activities of Anthos.","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8664094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39852528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

No limit to maximal lifespan in humans: how to beat a 122-year-old record. 人类最长寿命没有限制:如何打破122岁的纪录。

Oncoscience Pub Date : 2021-12-01 eCollection Date: 2021-01-01 DOI: 10.18632/oncoscience.547

Mikhail V Blagosklonny

{"title":"No limit to maximal lifespan in humans: how to beat a 122-year-old record.","authors":"Mikhail V Blagosklonny","doi":"10.18632/oncoscience.547","DOIUrl":"https://doi.org/10.18632/oncoscience.547","url":null,"abstract":"Although average human life expectancy is rising, the maximum lifespan is not increasing. Leading demographers claim that human lifespan is fixed at a natural limit around 122 years. However, there is no fixed limit in animals. In animals, anti-aging interventions (dietary restrictions, rapamycin, genetic manipulations) postpone age-related diseases and thus automatically extend maximum lifespan. In humans, anti-aging interventions have not been yet implemented. Instead, by treating individual diseases, medical interventions allow a patient to live longer (despite morbidity), expanding morbidity span. In contrast, slowly aging individuals (centenarians) enter very old age in good health, but, when diseases finally develop, they do not receive thorough medical care and die fast. Although the oldest old die from age-related diseases, death certificates often list \"old age\", meaning that diseases were not even diagnosed and even less treated. The concept of absolute compression of morbidity is misleading in humans (in truth, there is no other way to compress morbidity as by denying thorough medical care) and false in animals (in truth, anti-aging interventions do not condense morbidity, they postpone it). Anti-aging interventions such as rapamycin may potentially extend both healthspan and maximal lifespan in humans. Combining anti-aging medicine with cutting-edge medical care, regardless of chronological age, will extend maximal lifespan further.","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8636159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39696828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Correction: Targeting focal adhesion kinase overcomes erlotinib resistance in smoke induced lung cancer by altering phosphorylation of epidermal growth factor receptor. 纠正:靶向黏附激酶通过改变表皮生长因子受体的磷酸化来克服烟雾诱导肺癌的厄洛替尼耐药性。

Oncoscience Pub Date : 2021-09-23 eCollection Date: 2021-01-01 DOI: 10.18632/oncoscience.546

Hitendra S Solanki, Remya Raja, Alex Zhavoronkov, Ivan V Ozerov, Artem V Artemov, Jayshree Advani, Aneesha Radhakrishnan, Niraj Babu, Vinuth N Puttamallesh, Nazia Syed, Vishalakshi Nanjappa, Tejaswini Subbannayya, Nandini A Sahasrabuddhe, Arun H Patil, T S Keshava Prasad, Daria Gaykalova, Xiaofei Chang, Rachana Sathyendran, Premendu Prakash Mathur, Annapoorni Rangarajan, David Sidransky, Akhilesh Pandey, Evgeny Izumchenko, Harsha Gowda, Aditi Chatterjee

引用次数: 1

The hyperfunction theory of aging: three common misconceptions. 衰老的超功能理论：三个常见误解。

Oncoscience Pub Date : 2021-09-17 eCollection Date: 2021-01-01 DOI: 10.18632/oncoscience.545

Mikhail V Blagosklonny

引用次数: 0

Taking action early to manage emergence of acquired resistance to osimertinib or other third generation EGFR inhibitors. 及早采取行动，控制对奥西替尼或其他第三代EGFR抑制剂获得性耐药的出现。

Oncoscience Pub Date : 2021-09-15 eCollection Date: 2021-01-01 DOI: 10.18632/oncoscience.544

Guangzhi Ma, Shi-Yong Sun

引用次数: 1

Tune the channel: TRPM8 targeting in prostate cancer. 调谐频道:前列腺癌中的TRPM8靶向。

Oncoscience Pub Date : 2021-09-10 eCollection Date: 2021-01-01 DOI: 10.18632/oncoscience.543

Alessandro Alaimo, Dario De Felice, Sacha Genovesi, Marco Lorenzoni, Andrea Lunardi

{"title":"Tune the channel: TRPM8 targeting in prostate cancer.","authors":"Alessandro Alaimo, Dario De Felice, Sacha Genovesi, Marco Lorenzoni, Andrea Lunardi","doi":"10.18632/oncoscience.543","DOIUrl":"https://doi.org/10.18632/oncoscience.543","url":null,"abstract":"The therapeutic landscape of cancer treatments is quickly evolving thanks to the advent of precision oncology. Discovery of novel druggable targets and more reliable biomarkers is a primary objective towards personalized strategies of cancer treatment. Highly expressed in the prostate epithelium within the human body, Transient Receptor Potential subfamily M member 8 (TRPM8) levels rise in primary and hormone naïve metastatic prostate cancer (PCa) lesions, which makes this channel an interesting prototype of molecular target. Recently, by combining a multidisciplinary approach to an in vitro genetic platform, we demonstrated that the combination of potent TRPM8 agonists with X-rays induces a massive apoptotic response in radioresistant pre-malignant and malignant models of primary prostate lesions. As well, TRPM8 activation enhances the efficacy of docetaxel or enzalutamide in eradicating hormone naïve metastatic PCa cells. Overall, our findings provide a solid rationale for pursuing the pre-clinical and clinical study of TRPM8 as a valuable target for future approaches of precise oncology in PCa.","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39412577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Determining the utility of a screening program to reduce the incidence of HPV driven oropharyngeal cancer. 确定筛查程序的效用，以减少HPV驱动口咽癌的发病率。

Oncoscience Pub Date : 2021-08-09 eCollection Date: 2021-01-01 DOI: 10.18632/oncoscience.541

Sarju Vasani, Ian Frazer, Chamindie Punyadeera

{"title":"Determining the utility of a screening program to reduce the incidence of HPV driven oropharyngeal cancer.","authors":"Sarju Vasani, Ian Frazer, Chamindie Punyadeera","doi":"10.18632/oncoscience.541","DOIUrl":"https://doi.org/10.18632/oncoscience.541","url":null,"abstract":"The last decade has seen a continued escalation in rates of human papillomavirus related oropharyngeal malignancy (HPV-OPC). This has occurred despite established national vaccination programs. In contrast, HPV associated cervical cancer incidence rates have declined, due in part to effective cervical cancer screening programs, many of which have moved towards the detection of high-risk HPV (hrHPV) as an early marker of malignant potential. This raises questions as to whether similar hrHPV screening methods could be used for early detection of HPV-OPC. Persistent oral hrHPV is a prerequisite for the development of HPV-OPC and can be accurately detected in saliva. Despite this, single point saliva testing for hrHPV lacks sufficient sensitivity and specificity to allow for effective population screening. Recent published literature suggests the use of serial saliva testing in targeted high-risk individuals, with an emphasis on biomarker persistence and intensity patterns, as a potential means of detecting even subclinical microscopic disease. When coupled with serological testing, this has the potential to provide an accurate test for screening at risk individuals. Despite these promising developments, several significant barriers to an effective targeted screening program remain.","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39306765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

New insight into the role of MDMX in MDM2-mediated p53 degradation and anti-cancer drug development. MDMX在mdm2介导的p53降解和抗癌药物开发中的作用的新见解。

Oncoscience Pub Date : 2021-08-09 eCollection Date: 2021-01-01 DOI: 10.18632/oncoscience.542

Jing Yang, Yanping Zhang

引用次数: 0

Advances in culture methods for acute myeloid leukemia research. 急性髓系白血病培养方法研究进展。

Oncoscience Pub Date : 2021-08-04 eCollection Date: 2021-01-01 DOI: 10.18632/oncoscience.540

Krishnapriya Syama, Eman M Hassan, Shan Zou

引用次数: 1