Journal of cancer sciences最新文献

{"title":"Transcription Independent Stimulation of Telomerase Enzymatic Activity by HTLV-I Tax Through Stimulation of IKK.","authors":"M Bellon,&nbsp;Y Yuan,&nbsp;C Nicot","doi":"10.13188/2377-9292.1000024","DOIUrl":"https://doi.org/10.13188/2377-9292.1000024","url":null,"abstract":"<p><p>The persistence and spreading of HTLV-I infected cells relies upon their clonal expansion through cellular replication. The development of adult T cell leukemia (ATLL) occurs decades following primary infection by HTLV-I. Moreover, identical provirus integration sites have been found in samples recovered several years apart from infected individuals. These observations suggest that infected cells persist in the host for an extended period of time. To endure long term proliferation, HTLV-I pre-leukemic cells must acquire critical oncogenic events, two of which are the bypassing of apoptosis and replicative senescence. In the early stages of disease, interleukin-2 (IL-2)/IL-2R signaling likely plays a major role in combination with activation of anti-apoptotic pathways. Avoidance of replicative senescence in HTLV-I infected cells is achieved through reactivation of human telomerase (hTERT). We have previously shown that HTLV-I viral Tax transcriptionally activates the hTERT promoter. In this study we demonstrate that Tax can stimulate hTERT enzymatic activity independently of its transcriptional effects. We further show that this occurs through Tax-mediated NF-KB activating functions. Our results suggest that in ATLL cells acquire Tax-transcriptional and post-transcriptional events to elevate telomerase activity.</p>","PeriodicalId":91308,"journal":{"name":"Journal of cancer sciences","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8691565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39611091","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}

{"title":"Markers of Radiogenic Cancer vs. Tumor Progression: an Overview of Chernobyl Studies","authors":"Sergei V. Jargin","doi":"10.13188/2377-9292.1000025","DOIUrl":"https://doi.org/10.13188/2377-9292.1000025","url":null,"abstract":"Differences in the histological grade of malignancies may reflect diagnostic quality, that is, averagely earlier or later tumor detection in a given country. Studies of Chernobyl-related renal-cell carcinoma with a control from Spain and Colombia are discussed here in comparison with thyroid cancer research. It is concluded that suppositions about averagely higher grade and enhanced aggressiveness of malignancies from the areas previously contaminated by the Chernobyl fallout are unfounded and can lead to overtreatment. Results of many studies of Chernobyl-related malignancies are valuable; but conclusions should be reassessed taking into account that some cases, classified as aggressive radiogenic cancers, were in fact late-stage neglected malignancies. Associations of various markers with the tumor progression can become a field for the future research and re-interpretation of data obtained in studies comparing malignancies from different countries. Some markers may reflect efficiency of healthcare services. Citation: Citation: Jargin SV. Markers of Radiogenic Cancer vs. Tumor Progression: an Overview of Chernobyl Studies. J Cancer Sci. 2021;8(1): 7 J Cancer Sci 8(1): 7 (2021) Page 02 ISSN: 2377-9292 but the statistical significance vanished if only doses <200 mSv were considered [19,20]. Doses <100 mGy at low rates may induce adaptive response against neoplastic transformation [21]. Annual average doses from natural radiation should be specified in papers where cohorts from different geographical regions are compared; otherwise doses among controls may turn out to be not significantly different from those in the “exposed” cohort e.g. in patients from Spain vs. those from Kiev [6,8]. The average annual individual dose from the background radiation in Spain is ~5 mSv [22,23]. According to an estimate, the mean whole-body individual dose to inhabitants of Kiev from all sources was ≤10 mSv in 1986, decreasing thereafter [24]. No dose estimates were given in the articles [4-10]; it is only written with a self-reference: “This observation also supports the prevailing suspicion [9] that in Ukraine the radiation contamination levels were similar within and beyond the officially-established 80-km extent of radiation contamination around Chernobyl [25]” [10]. The source [25], a Ministry report, has been unavailable. Radiation Effects vs. Late Detection The Chernobyl accident (CA) provides an example of considerable difference in diagnostic quality before and after the accident. There has been no convincing evidence of cause-effect relationships between radiation exposures from CA and the incidence increase of cancers in residents of contaminated territories other than TC in people exposed at a young age [18]. TC and probably also other cancers were underreported before CA. Mechanisms of the registered TC incidence increase included the screening and improved medical surveillance after CA [18]. According to the UNSCEAR, “the background rate of thyroid ca","PeriodicalId":91308,"journal":{"name":"Journal of cancer sciences","volume":"62 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66211714","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}

{"title":"Molecular Profiling for Patients with Solid Tumors: A Single- Institution Experience","authors":"C. P. Ong","doi":"10.13188/2377-9292.1000023","DOIUrl":"https://doi.org/10.13188/2377-9292.1000023","url":null,"abstract":"Molecular Profiling (MP) of tumors is innovative progress that led to identifying targetable alterations that could be exploited to deliver personalized cancer treatment. Lack of data from the region about the clinical utility of has prompted this study. Tumor tissues from 100 consecutive adult patients with solid tumors were genomically profiled successfully using commercially available platforms. Outcomes for patients who received an MP-guided versus MP-unguided therapy were compared. Progression-Free Survival (PFS) was the primary endpoint, while Overall Survival (OS) was the secondary endpoint. Patients’ median age was 57 years, and female patients constituted 65% of the series. Thirty-one patients were newly diagnosed, and 69 patients had the MP performed upon disease recurrence or progression. Breast, lung, and colorectal cancers were the most frequent tumors. In 90 of the tested tumors, one or more aberrations were identified. In 61 patients, the MP results suggested at least one matched agent and guided therapy in 53 patients. Of all patients who received further therapy (83 patients), the median PFS was significantly longer in patients whose MP-guided versus those whose treatment was not guided (21.8 [95% CI; 14.5 - 29.1] vs. 10.9 [95% CI; 6.2 - 15.6] months, hazard ratio [HR] = 0.34 [95% CI; 0.17 - 0.69], P = 0.002). The benefit was largely shown in patients with recurrent or progressive disease (HR = 0.32 [95% CI; 0.14 - 1.20.75]; P = 0.006). While patients who received MP-guided therapy had numerically higher OS rates, that difference was not significant. This preliminary experience demonstrated MP’s feasibility for cancer patients with a significant improvement in PFS, albeit a lack of OS benefit. Further research is warranted to address the inherent challenges for the universal adoption of MP in daily practice.","PeriodicalId":91308,"journal":{"name":"Journal of cancer sciences","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42601262","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}

{"title":"Breast Cancer Classification: A CAD System for a Combined Use of Elastography and B-Mode Sonography","authors":"Fleury Efc, H. Schiabel","doi":"10.13188/2377-9292.1000022","DOIUrl":"https://doi.org/10.13188/2377-9292.1000022","url":null,"abstract":"Purpose: The aim of this study was to evaluate and compare the diagnostic performance of elastography, B-mode Ultrasound (US), and a combination of elastography and B-mode US for the differentiation between benign and malignant lesions. Methods: A prospective study was carried out from July to December 2015, which 87 patients with 83 lesions were examined with conventional B-mode ultrasound and strain elastography. All the lesions had been proven by biopsy, resulting in 31 malignant and 52 benign lesions. A radiologist with 16 years of experience classified visually these cases. We also used a CAD sys-tem to classify the lesions classified visually by the most experienced radiologist and using a CAD system. The data obtained were compared with the results provided by another radiologist and a resident with 2 years of experience. Sensitivity, specificity and AUC for the three observers using the CAD system were calculated. Results: The developed CADx system provided a diagnostic concordance in the classification of breast lesions from the different ways of contour determination (manual and automatic), allowing to reduce the diagnostic variability. In addition, the CADx system showed superior results to the visual analysis of the radiologist. When the radiologist associated both examinations (B-mode ultrasound and elastography), his visual analysis provided 87.1%, 55.8% and 0.714 of sensitivity, specificity and AUC, respectively. When we considered the result provided by the association between B-mode ultrasound and elastography images, the CADx system provided a comparative increase of about 7% of sensitivity and 17.2% of specificity, using the contour delimited by the most experienced radiologist. In addition, a positive influence was observed in the use of the computational tool by radiologists, since, on average, their sensitivity and specificity indexes also increased in relation to the conventional analysis, from 87.1% and 55.8% to 90.3% and 73.1%, respectively. Conclusion: Thus, it can be concluded that the developed CADx system performed well in distinguishing benign from malignant lesions for both B-mode ultrasound and elastography. The AUC obtained was higher than the radiologist’s visual analysis in most of the cases analyzed. Citation: Marcomini KD, Fleury EFC, Schiabela H. Breast Cancer Classification: A CAD System for a Combined Use of Elastography and B-Mode Sonography. J Cancer Sci. 2020;7(1): 6. J Cancer Sci 7(1): 6 (2020) Page 02 ISSN: 2377-9292","PeriodicalId":91308,"journal":{"name":"Journal of cancer sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45947173","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}

{"title":"NOTCH1 Activation Depletes the Pool of Side Population Stem Cells in ATL.","authors":"Xue Tao Bai,&nbsp;Chien-Hung Yeh,&nbsp;Christophe Nicot","doi":"10.13188/2377-9292.1000013","DOIUrl":"https://doi.org/10.13188/2377-9292.1000013","url":null,"abstract":"<p><strong>Background: </strong>HTLV-I infection is associated with the development of adult T-cell leukemia (ATL), a malignancy characterized by a high rate of disease relapse and poor survival. Previous studies reported the existence of side population (SP) cells in HTLV-I Tax transgenic mouse models. These studies showed that these ATL-like derived SP cells have both self-renewal and leukemia renewal capacity and represent Cancer Stem Cells (CSC)/Leukemia-Initiating Cells (LIC). Since CSC/LIC are resistant to conventional therapies, a better characterization is needed.</p><p><strong>Methods: </strong>We isolated, sorted and characterized SP cells from uncultured PBMCs from ATL patients and from ATL patient-derived cell lines. We then identified several specific signaling pathways activated or suppressed in these cells. Expression of viral gene HBZ and Tax transcriptional activity was also investigated. Using gamma-secretase inhibitor (GSI, Calbiochem) and stably transduced ATL cell lines expressing TET-inducible NOTCH 1 intracellular domain (NICD), we characterized the role of activated NOTCH 1 in the maintenance of the SP cells in ATL.</p><p><strong>Results: </strong>Our studies confirm the existence of SP cells in ATL samples. These cells demonstrate lower activation of NOTCH1 and Tax, and reduced expression of STAT3, β-catenin/Wnt3 and viral HBZ. We further show that PI3K and the NOTCH1 signaling pathway have opposite functions, and constitutive activation of NOTCH1 signaling depletes the pool of SP cells in ATL-derived cell lines.</p><p><strong>Conclusions: </strong>Our results suggest that in ATL, a balance between activation of the NOTCH1 and PI3K signaling pathway is the key in the control of SP cells maintenance and may offer therapeutic opportunities.</p>","PeriodicalId":91308,"journal":{"name":"Journal of cancer sciences","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5596512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35521243","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}

{"title":"HTLV-I Tax-Mediated Inactivation of Cell Cycle Checkpoints and DNA Repair Pathways Contribute to Cellular Transformation: \"A Random Mutagenesis Model\".","authors":"C. Nicot","doi":"10.13188/2377-9292.1000009","DOIUrl":"https://doi.org/10.13188/2377-9292.1000009","url":null,"abstract":"To achieve cellular transformation, most oncogenic retroviruses use transduction by proto-oncogene capture or insertional mutagenesis, whereby provirus integration disrupts expression of tumor suppressors or proto-oncogenes. In contrast, the Human T-cell leukemia virus type 1 (HTLV-I) has been classified in a separate class referred to as \"transactivating retroviruses\". Current views suggest that the viral encoded Tax protein transactivates expression of cellular genes leading to deregulated growth and transformation. However, if Tax-mediated transactivation was indeed sufficient for cellular transformation, a fairly high frequency of infected cells would eventually become transformed. In contrast, the frequency of transformation by HTLV-I is very low, likely less than 5%. This review will discuss the current understanding and recent discoveries highlighting critical functions of Tax in cellular transformation. HTLV-I Tax carries out essential functions in order to override cell cycle checkpoints and deregulate cellular division. In addition, Tax expression is associated with increased DNA damage and genome instability. Since Tax can inhibit multiple DNA repair pathways and stimulate unfaithful DNA repair or bypass checkpoints, these processes allow accumulation of genetic mutations in the host genome. Given this, a \"Random Mutagenesis\" transformation model seems more suitable to characterize the oncogenic activities of HTLV-I.","PeriodicalId":91308,"journal":{"name":"Journal of cancer sciences","volume":"2 2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66211605","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}