Thyroid carcinoma consists a group of phenotypically heterogeneous cancers. Recent advances in biological technologies have been advancing the delineation of genetic, epigenetic, and non-genetic ...factors that contribute to the heterogeneities of these cancers. In this review article, we discuss new findings that are greatly improving the understanding of thyroid cancer biology and facilitating the identification of novel targets for therapeutic intervention. We review the phenotypic features of different subtypes of thyroid cancers and their underlying biology. We discuss recent discoveries in thyroid cancer heterogeneities and the critical mechanisms contributing to the heterogeneity with emphases on genetic and epigenetic factors, cancer stemness traits, and tumor microenvironments. We also discuss the potential relevance of the intratumor heterogeneity in understanding therapeutic resistance and how new findings in tumor biology can facilitate designing novel targeting therapies for thyroid cancer.
Tumor recurrence following treatment remains a major clinical challenge in oral cavity cancer. Cancer stem cells (CSCs) have been isolated from human oral cancers and been considered as the driving ...force of tumor recurrence and metastasis. However, it still remains unclear whether targeting CSCs in oral cancer is a clinically relevant strategy to combat cancer recurrence and metastasis. Here, using clinical cancer specimens and patient-derived xenografts, we show that the self-renewal regulator BMI1 is highly expressed in CSCs of oral cavity squamous cell carcinoma. Inhibition of BMI1 decreases oral CSCs' self-renewal and tumor-initiating potential. Treatment of pre-established human oral cancer xenografts with a BMI1 inhibitor resulted in abrogation of tumor progression and reduced the frequency of CSCs in the xenografts. Remarkably, the BMI1 inhibitor has therapeutic effects in cisplatin-resistant tumors and can reduce metastases initiated by circulating CSCs. Mechanistically, BMI1-inhibition leads to oral CSC necroptotic cell death, which underlies the self-renewal impairment after inhibiting BMI1. Our data provide a pre-clinical proof-of-concept that targeting BMI1-related CSC self-renewal is a clinically relevant anti-cancer therapy in human oral cavity squamous cell carcinoma.
JS001, a humanized IgG
monoclonal antibody against the programmed death-1 (PD-1) receptor, blocks the interaction of PD-1 with its ligands and promotes T cell activation in preclinical studies. This ...phase I study is designed to evaluate the safety, tolerability, and clinical activity of JS001 in advanced melanoma or urologic cancer patients who are refractory to standard systemic therapy.
In the dose escalation cohorts, subjects initially received a single-dose, intravenous infusion of JS001, and were followed for 28 days followed by multi-dose infusions every 2 weeks. In the dose expansion cohorts, subjects received multi-dose infusions every 2 weeks. Clinical response was evaluated after each 8-week treatment cycle according to RECIST v1.1 criteria.
Thirty-six subjects diagnosed with advanced melanoma (n = 22), urothelial cancer (UC) (n = 8), or renal cell cancer (RCC) (n = 6) were enrolled. Melanoma subjects included 14 acral and 4 mucosal subtypes. JS001 was well tolerated, and no dose-limiting toxicity was observed. By the safety data cutoff date, 100% of subjects had treatment-related adverse events (TRAE) with most adverse events being grade 1 or 2, and ≥ grade 3 TRAEs occurred in 36%. Among all 36 subjects, 1 confirmed complete response (acral melanoma), 7 confirmed partial responses (2 acral melanoma, 1 mucosal melanoma, 2 UC, and 2 RCC), and 10 stable disease were observed, for an objective response rate of 22.2% (95% CI, 10.1 to 39.2), and a disease control rate of 50.0% (95% CI, 32.9 to 67.1). Clinical responses were correlated with PD-L1 expression on tumor cells, the presence of tumor infiltrating lymphocytes (TIL), baseline tumor volume, ECOG performance status, serum LDH levels, high percentage of activated CD8+ T cells and CD3- CD16+ CD54+ NK cells in the peripheral blood as well as tumor mutational burden (TMB).
JS001 was well tolerated and demonstrated promising anti-tumor activity in UC and RCC as well as in previously underexplored acral and mucosal melanoma subtypes. Subjects with an immune-active profile in the tumor microenvironment or in peripheral blood responded favorably to JS001 treatment. The completion of the current phase I study has led to the initiation of the first prospective anti-PD-1 registration trial in Asia focusing on acral and mucosal melanoma subtypes, representative of the regional disease epidemiology.
Clinical Trial ID: NCT02836795 , registered July 19, 2016, retrospectively registered.
Liver cancer is the second highest cause of cancer-related deaths worldwide. It is commonly treated with liver transplantation, where tacrolimus is typically used as an antirejection ...immunosuppressant. The purpose of this study was to evaluate the effect of tacrolimus time in therapeutic range (TTR) on liver cancer recurrence in liver transplant recipients and to compare the performance of TTRs calculated according to the target ranges recommended in published guidelines.
A total of 84 patients who underwent liver transplantation for liver cancer were retrospectively included. Tacrolimus TTR was calculated using linear interpolation from the date of transplantation until recurrence or the last follow-up according to target ranges recommended in the Chinese guideline and international expert consensus.
Twenty-four recipients developed liver cancer recurrence after liver transplantation. The CTTR (TTR calculated according to the Chinese guideline) for the recurrence group was significantly lower than that of the nonrecurrence group (26.39% vs. 50.27%, P < 0.001), whereas the ITTR (TTR calculated according to the international consensus) was not significantly different between the two groups (47.81% vs. 56.37%, P = 0.165). Multivariate survival analysis revealed that age, microvascular invasion, hepatocellular carcinoma, CTTR, and mean tacrolimus trough concentration were independent predictors of liver cancer recurrence after liver transplantation.
TTR predicts liver cancer recurrence in liver transplant recipients. The range of tacrolimus concentrations recommended in the Chinese guideline was more beneficial than that recommended in the international consensus for Chinese patients undergoing liver transplantation for liver cancer.
Abstract
Extending the benefits of tumor molecular profiling for all cancer patients requires a comprehensive analysis of tumor genomes across distinct patient populations worldwide. In this study, ...we perform deep next-generation DNA sequencing (NGS) from tumor tissues and matched blood specimens from over 10,000 patients in China by using a 450-gene comprehensive assay, developed and implemented under international clinical regulations. We perform a comprehensive comparison of somatically altered genes, the distribution of tumor mutational burden (TMB), gene fusion patterns, and the spectrum of various somatic alterations between Chinese and American patient populations. Here, we show 64% of cancers from Chinese patients in this study have clinically actionable genomic alterations, which may affect clinical decisions related to targeted therapy or immunotherapy. These findings describe the similarities and differences between tumors from Chinese and American patients, providing valuable information for personalized medicine.
To the more deeply understand the enhancement heat transfer mechanism and optimization design for wavy fin-and-flat tube heat exchangers, three-dimensional numerical simulations and experimental ...investigation of air flow and heat transfer characteristics over the wavy fin heat exchangers are presented in this study. The numerical simulation results compared with the wind tunnel test data, the results show that the numerical simulation results are in good with the test. The experimental results show that, in the range of
Re = 1000–5500, the standard
k-
ε mode (SST) is more suitable to predict the air flow and heat transfer of wavy fin. The waviness amplitude has the distinct effect on the heat transfer and pressure drop of wavy fin, while the wavy fin profile (Triangular, Sinusoidal and Triangular round corner) has little effect on the heat transfer performance. In additional, the enhancement heat transfer mechanism of wavy fin is explained in view of field synergy principle. Reduction the synergy angle between velocity and temperature gradient will induce to the heat transfer coefficients increase of wavy fin.
The novel coronavirus disease 2019 (COVID-19) pandemic has changed the medical education platform for students in the United States of America (USA). In that light, medical schools had to rapidly ...rearrange the dynamics of their educational curricula from the traditional platforms, to incorporate telemedicine. The telemedicine platform is supported in many specialties, allowing students various options to continue their education without interruption during the COVID-19 pandemic, and beyond. Telemedicine platforms are projected to grow exponentially due to the COVID-19 pandemic, allowing a segue for medical schools to modify their curricula by incorporating telemedicine programs. These distant-, e-learning (tele-education) programs align with the recommendations and guidelines for practicing social distancing. In this article, we surveyed fourth-year medical students to better understand their views on multiple aspects of e-learning, and its impact on their medical education during the COVID-19 pandemic. We assessed the medical students' experiences, satisfaction, insight and knowledge with e-learning, tele-education, telehealth, and their related modalities during COVID-19. We provide an organized overview and analysis of the main factors that influence medical education during the COVID-19 pandemic, while bringing forth the main challenges, limitations, and emerging approaches in the field of telemedicine and its application as it relates to medical education and e-learning across medical specialties. We outline the main themes and ideas that the medical students voiced, as to how their medical education is being impacted by the COVID-19 pandemic and how they will incorporate telemedicine and tele-education in their future career. A cross-sectional, mixed-method survey was developed and distributed via Google Surveys to 181 University at Buffalo, Jacobs School of Medicine and Biomedical Sciences, United States of America, 4th year medical students, in December 2020. Results were compiled and analyzed after a 6-day open period for responses to be submitted. The survey instrument consisted of questions that inquire about the students' perspectives as it relates to their rapid switch from their traditional method of learning to the on-line version of medical education during the COVID-19 pandemic. A total of 65 students responded to the survey, of which 63 completed the survey. More than half of the students (
= 63, 57%) indicated that both their specialty of interest, and (
= 21, 33%) their sub-internships were impacted by the temporary lockdown, due to the COVID-19 pandemic. Students also indicated that the top three specialties that were affected included surgery, internal medicine and obstetrics and gynecology. When the students were asked if they were satisfied with the use of aquifer for their health care e-learning, only 35% of the students were satisfied. The students expressed that the school's administration team did a good job in developing the new tele-education curriculum for those in clinical training. In addition, responses indicated that students were open to case-based video learning and readings, when combined with the abbreviated clinical exposure during the make-up "clinical immersions periods" allowed for adequate learning. Overall, the survey responses show that more than half, approximately 54% of the medical students utilized telemedicine platforms during their clerkships that were impacted by COVID-19. The 4th-year medical students did not find tele-education and e-learning to be as effective as traditional medical education that combines in-person didactic classroom instructions and in-person face-to-face in hospital clerkships. Students felt that the telemedicine program that was rapidly set up due to the COVID-19 'lockdown' was fragmented, since it was not a formal integration of a telemedicine E-learning program. Students would have preferred more 'real' cases to follow, instead of the ready-made, aquifer type of cases. Telemedicine has significant potential to address many of the challenges facing the medical education environment today. We believe now that people have become comfortable with this method of teaching, that even after the pandemic ends, we will continue to see tele-education used as a platform for medical education.
Background
The COVID-19 outbreak has tremendously impacted the world. The number of confirmed cases has continued to increase, causing damage to society and the economy worldwide. The public pays ...close attention to information on the pandemic and learns about the disease through various media outlets. The dissemination of comprehensive and accurate COVID-19 information that the public needs helps to educate people so they can take preventive measures.
Objective
This study aimed to examine the dissemination of COVID-19 information by analyzing the information released by the official WeChat account of the People’s Daily during the pandemic. The most-read COVID-19 information in China was summarized, and the factors that influence information dissemination were studied to understand the characteristics that affect its dissemination. Moreover, this was conducted in order to identify how to effectively disseminate COVID-19 information and to provide suggestions on how to manage public opinion and information governance during a pandemic.
Methods
This was a retrospective study based on a WeChat official account. We collected all COVID-19–related information, starting with the first report about COVID-19 from the People’s Daily and ending with the last piece of information about lifting the first-level emergency response in 34 Chinese provinces. A descriptive analysis was then conducted on this information, as well as on Qingbo Big Data’s dissemination index. Multiple linear regression was utilized to study the factors that affected information dissemination based on various characteristics and the dissemination index.
Results
From January 19 to May 2, 2020, the People’s Daily released 1984 pieces of information; 1621 were related to COVID-19, which mainly included headline news items, items with emotional content, and issues related to the pandemic’s development. By analyzing the dissemination index, seven information dissemination peaks were discerned. Among the three dimensions of COVID-19 information—media salience, content, and format—eight factors affected the spread of COVID-19 information.
Conclusions
Different types of pandemic-related information have varying dissemination power. To effectively disseminate information and prevent the spread of COVID-19, we should identify the factors that affect this dissemination. We should then disseminate the types of information the public is most concerned about, use information to educate people to improve their health literacy, and improve public opinion and information governance.
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