High Grade
Recently Published Documents


(FIVE YEARS 11078)



2021 ◽  
Vol 3 (Supplement_4) ◽  
pp. iv1-iv1
Asher Marks ◽  
Ranjit Bindra

Abstract DESCRIPTION The lack of enrollment of AYA patients on clinical trials is well documented and multivariant. Here we present the basic science, examination of its relevance to the AYA population specifically, and the parallel deployment of two international clinical trials via a pediatric neuro-oncology and adult brain tumor consortium. DISCUSSION In February of 2017, the laboratory of Ranjit Bindra, MD, PhD, published a manuscript describing the finding that tumors with IDH1/2 mutations induce a BRCAness state leading to PARP inhibitor (PARPi) sensitivity and synergistic interactions with temozolomide chemotherapy [2]. Despite IDH1/2 mutations being rare in the pediatric high-grade glioma population, three independent groups confirmed that the incidence is significantly increased to ~30% in the adolescent and young adult (AYA) population. Upon discovery of a high blood-brain-barrier penetrant, high potency PARPi by BeiGene Pharmaceuticals, an international trial was launched through the Pacific Pediatric Neuro-Oncology Consortium (PNOC) [3] to test this drug in an AYA specific trial recruiting patients ages 13 to 25, with a concurrent trial being run for patients older than 25 years of age through the Adult Brain Tumor Consortium (ABTC) [4]. While most trials that enroll AYA patients are forced to assess them as a unique cohort in post-analysis, if at all, the PNOC trial mentioned above was designed from the ground up with the AYA population in mind. It has allowed us to base initial dosing, recruitment strategies, psychosocial assessments, and outcomes, specifically on the AYA population. Ultimately, we expect their distinctive biology to yield unique results when compared to the ABTC trial. We propose that this is a model that could potentially be replicated in other disease processes and early phase drugs with the buy-in of the pharmaceutical industry and early phase consortiums. Acknowledgements: BeiGene Pharmaceuticals, PNOC, ABTC, CureSearch, Gateway Foundation

Dorothee Cäcilia Spille ◽  
Alborz Adeli ◽  
Peter B. Sporns ◽  
Katharina Heß ◽  
Eileen Maria Susanne Streckert ◽  

2021 ◽  
Vol 8 ◽  
Xiaopei Chao ◽  
Lan Wang ◽  
Shu Wang ◽  
Jinghe Lang ◽  
Xianjie Tan ◽  

Vaginal microbiome may have a role in HPV infection and cervical neoplasm. To explore potential vaginal microbiome biomarkers for high-grade squamous intraepithelial lesion (HSIL), and to find the best scheme to facilitate the current cervical cancer screening strategy. This study enrolled 272 women, including 83 confirmed with HSIL, 86 with HPV infection but without cervical neoplasm, and 103 without HPV infection as controls. Vaginal microbiome composition was determined by sequencing of barcoded 16S rDNA gene fragments (V4) on Illumina HiSeq2500. The relative increasing abundance of Stenotrophomonas, Streptococcus, and Pseudomonas, and a concomitant paucity of Dialister, unidentified Prevotellaceae, Faecalibacterium, Bifidobacterium, and Bacteroides, were related with HSIL, which can be used to predict the development of HISL in high-risk HPV infected patients. The relative abundance of Stenotrophomonas being over 0.0090387%, or Faecalibacterium being under 0.01420015%, or Bifidobacterium being under 0.0116183% maybe a good predictor for HSIL for those infected with HPV 16 and/or 18. The relative abundance of Stenotrophomonas being over 0.01549105%, or Streptococcus being over 0.48409585%, or Bacteroides being under 0.0296912% maybe a good predictor for HSIL for those infected with the 12 other high-risk types of HPV with concurrent abnormal TCT results. This study revealed that potential vaginal microbiome biomarkers may relate to HSIL, and can facilitate the cervical cancer screening.

A.M. Celal Şengör ◽  
Nalan Lom ◽  
Ali Polat

To the memory of Nicholas John (Nick) Archibald (1951−2014), master of cratonic geology. Cratons, defined by their resistance to deformation, are guardians of crustal and lithospheric material over billion-year time scales. Archean and Proterozoic rocks can be found in many places on earth, but not all of them represent cratonic areas. Some of these old terrains, inappropriately termed “cratons” by some, have been parts of mobile belts and have experienced widespread deformations in response to mantle-plume-generated thermal weakening, uplift and consequent extension and/or various plate boundary deformations well into the Phanerozoic. It is a common misconception that cratons consist only of metamorphosed crystalline rocks at their surface, as shown by the indiscriminate designation of them by many as “shields.” Our compilation shows that this conviction is not completely true. Some recent models argue that craton formation results from crustal thickening caused by shortening and subsequent removal of the upper crust by erosion. This process would expose a high-grade metamorphic crust at the surface, but greenschist-grade metamorphic rocks and even unmetamorphosed supracrustal sedimentary rocks are widespread on some cratonic surfaces today, showing that craton formation does not require total removal of the upper crust. Instead, the granulitization of the roots of arcs may have been responsible for weighing down the collided and thickened pieces and keeping their top surfaces usually near sea level. In this study, we review the nature and origin of cratons on four well-studied examples. The Superior Province (the Canadian Shield), the Barberton Mountain (Kaapvaal province, South Africa), and the Yilgarn province (Western Australia) show the diversity of rocks with different origin and metamorphic degree at their surface. These fairly extensive examples are chosen because they are typical. It would have been impractical to review the entire extant cratonic surfaces on earth today. We chose the inappropriately named North China “Craton” to discuss the requirements to be classified as a craton.

2021 ◽  
Binxiang Zhu ◽  
Yinmin Dong ◽  
Hongyu Zhu ◽  
Zijian Dong ◽  
Feng Li

Abstract Background. As chondrosarcoma is the second highest primary malignant tumor of bone, it is necessary to find a way to predict the prognosis of chondrosarcoma. But the current model rarely involves the study of competing risk. This is a retrospective study with the aim of establishing a prognostic model and a nomogram based on competing risk to predict the probability of cancer-specific death (CSD) at 3 and 5 years. The Fine and Gray regression is a targeted statistical method, which makes the results more authentic and reliable.Methods. A total of 1674 chondrosarcoma patients were identified from the SEER database, and they were divided into training cohort and validation cohort by year of diagnosis. These two cohorts were used to develop and validate the prognostic model to predict the 3-year and 5-year probabilities of CSD, with non-CSD as the competing risk. Model accuracy made use of some verification functions, such as C-index, receiver operating characteristic curve (ROC), calibration plot, area under curve (AUC) and Brier score.Results. According to the outcomes of the model: older age (subdistribution hazards ratio(95%CI): 1.02 (1.01-1.03); P<0.001), dedifferentiated CHS (SHR(95%CI): 2.16 (1.30-3.59); P=0.003), high grade (SHR(95%CI): 2.60 (1.83-3.68); P<0.001), Regional involvement (SHR(95%CI): 3.15 (2.01-4.93); P<0.001), Distant metastasis (SHR(95%CI): 11.56 (6.82-19.59); P<0.001), tumor excision (SHR(95%CI): 0.47 (0.25-0.87); P=0.02) and Radical resection (SHR(95%CI): 0.54 (0.32-0.90); P=0.02) were significantly. They obviously promoted the increase of CSD.Conclusion. This prognostic model considered the competing risks of chondrosarcoma, and the nomogram can effectively predict the probability of CSD in patients with chondrosarcoma, which is suitable for clinical application.

2021 ◽  
Vol 8 ◽  
Jun Ding ◽  
Haiou Xu ◽  
Lihua Xia ◽  
Shanshan Cao ◽  
Qing Wu

Objectives: To compare the performance and outcomes of monopolar electrosurgical conization (MESC) or the loop electrosurgical excision procedure (LEEP) in the treatment of high-grade squamous intraepithelial lesion (HSIL).Methods: This retrospective study included 554 patients diagnosed with HSIL through biopsy. The study used either LEEP or MESC for cervical conization. Additionally, the medical records of these patients, including the basic information, status of the excision margin, cone depth, cone width, fragmentation, complication, and the results of a 6-month follow-up after conization, were reviewed.Results: Compared to MESC, LEEP had a significantly higher rate of positive endocervical margin (3.77 vs. 8.65%; p = 0.018), burn injury of the margin (4.90 vs. 10.38%; p = 0.016) and a lower rate of adequate cone depth (83.40 vs. 89.62%; p = 0.034). In addition, LEEP was significantly more likely to cause fragmentation (p = 0.000). There was, however, no significant difference in the rate of abnormal cervical cytology and positive high-risk HPV (hrHPV) between these two groups, 6 months after cervical conization.Conclusion: Both LEEP and MESC appeared to be equally effective in the clinical treatment of HSIL. Nonetheless, MESC resulted in a better pathological outcome with regard to the status of the margin, tissue fragmentation, and cone depth.

2021 ◽  
Vol 16 (1) ◽  
Sofia Liou ◽  
Neshat Nilforoushan ◽  
Yuna Kang ◽  
Neda A. Moatamed

Abstract Background The aim of this study was to determine how Stathmin-1 and Heat Shock Protein 27 (HSP27) can be used as adjunctive biomarkers to differentiate high-grade dysplasia from benign/reactive lesions in cervical tissues. In addition, we aimed to see if any of these markers can differentiate endometrial from endocervical adenocarcinomas. Methods Fifty cases including benign cervical tissue, low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), adenocarcinoma in situ of the endocervix, invasive endocervical adenocarcinoma, and endometrial adenocarcinoma were selected. Stathmin-1 and HSP27 immunohistochemistry (IHC) were performed for each case and the results were compared to the previously available p16 IHC stains. Results p16 stained positively in 100% of HSIL, endocervical adenocarcinoma in situ, and invasive endocervical cases. Stathmin-1 stained positively in 43% of HSIL and 90% of endocervical adenocarcinoma in situ and all invasive endocervical cases. Stathmin-1 and p16 were negative in all benign cervical samples. Stathmin-1, HSP27, and p16 stained 100% of LSIL cases. HSP27 stained indiscriminately, including 100% of benign cervical tissue. 87% of the endometrial adenocarcinomas stained positively for p16, Stathmin-1, and HSP27. Conclusion p16 remains superior to both Stathmin-1 and HSP27 in differentiating dysplasia from benign, reactive changes of the cervix.

2021 ◽  
Vol 12 (1) ◽  
John DeSisto ◽  
John T. Lucas ◽  
Ke Xu ◽  
Andrew Donson ◽  
Tong Lin ◽  

AbstractRadiation-induced high-grade gliomas (RIGs) are an incurable late complication of cranial radiation therapy. We performed DNA methylation profiling, RNA-seq, and DNA sequencing on 32 RIG tumors and an in vitro drug screen in two RIG cell lines. We report that based on DNA methylation, RIGs cluster primarily with the pediatric receptor tyrosine kinase I high-grade glioma subtype. Common copy-number alterations include Chromosome (Ch.) 1p loss/1q gain, and Ch. 13q and Ch. 14q loss; focal alterations include PDGFRA and CDK4 gain and CDKN2A and BCOR loss. Transcriptomically, RIGs comprise a stem-like subgroup with lesser mutation burden and Ch. 1p loss and a pro-inflammatory subgroup with greater mutation burden and depleted DNA repair gene expression. Chromothripsis in several RIG samples is associated with extrachromosomal circular DNA-mediated amplification of PDGFRA and CDK4. Drug screening suggests microtubule inhibitors/stabilizers, DNA-damaging agents, MEK inhibition, and, in the inflammatory subgroup, proteasome inhibitors, as potentially effective therapies.

2021 ◽  
Shahan Mamoor

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer (1). We performed discovery of genes associated with epithelial ovarian cancer and of the high-grade serous ovarian cancer (HGSC) subtype, using published and public microarray data (2, 3) to compare global gene expression profiles of normal ovary or fallopian tube with that of primary tumors from women diagnosed with epithelial ovarian cancer or HGSC. We identified the gene encoding RAS-like estrogen regulated growth inhibitor, RERG, as among the genes whose expression was most different in epithelial ovarian cancer as compared to the normal fallopian tube. RERG expression was significantly lower in high-grade serous ovarian tumors relative to normal fallopian tube. In a separate dataset, we discovered significant differential expression of a non-coding RNA transcribed from the RERG locus, RERG-AS1, in the tumors of patients with epithelial ovarian cancer when comparing tumors based on disease progression. RERG expression correlated with progression-free survival in patients with ovarian cancer. These data indicate that expression of RERG is perturbed in epithelial ovarian cancers broadly and in ovarian cancers of the HGSC subtype. RERG may be relevant to pathways underlying ovarian cancer initiation (transformation) or progression.

Sign in / Sign up

Export Citation Format

Share Document