教学课程资源库 更多>>

关键词： Stem cell   Acid   Acidity   Pluripotency   Pluripotent   Zinc   SSEA-4   Oct4  

摘要： Environmental changes can stress and alter biology at the molecular and cellular level. For example, metal-protein interaction is a classic physic and biological property of nature, which is fundamentally influenced by acidity. Here, we report a unique cellular reprogramming phenomenon in that a brief strong acid treatment induced the expression of pluripotent stem cell (PSC) markers. We used strong acid to briefly challenge mix-cultured gastric cells, and then subcultured survived cells in a normal cell culture medium. We found that survival acid-treated cells expressed PSC markers detected by commonly used pluripotent antibodies such as SSEA-4 and Oct4. In addition, we observed that the survived cells from the acid challenge grew faster during the second and third weeks of subculture and had a relative short doubling time (DT) than the controls. PSC marker-labeled 'older' cells also presented immature cell-like morphology with some having marker Oct4 in the nucleus. Finally, the expression of the markers appeared to be sensitive to metal ion chelation. Removal of the metals during a brief acid treatment reduced pluripotent marker-positive cells, suggesting the dissociation of metals from metal-binding proteins may be a factor involved in the induction of stem cell markers. Our findings reveal that somatic cells appear to possess a plasticity feature to express pluripotent marker proteins or to select cell subpopulations that express pluripotent marker proteins when cells are transiently exposed to strong acid. It opens new directions for understanding conserved regulatory mechanisms involved in cellular survival under stressful stimulation.

关键词： Neuroendocrine neoplasm   Neuroendocrine carcinoma   Mixed neuroendocrine   non-neuroendocrine neoplasm   Urinary bladder  

摘要： Neuroendocrine carcinomas (NECs) of the urinary bladder are very rare and can be observed in the context of mixed neuroendocrine/non-neuroendocrine neoplasms (MiNENs), most frequently in association with urothelial carcinoma. Small cell NECs are far more common than large cell NECs (LCNECs), which are exceedingly rare. We describe a primary MiNEN of the urinary bladder, composed of a LCNEC and of an adenocarcinoma, in which the neuroendocrine component reached complete pathological regression after neoadjuvant M-VAC chemotherapy, whereas the non-neuroendocrine component of the tumor progressed to metastatic disease. Compared to mixed neuroendocrine/non-neuroendocrine neoplasms described in the literature until now, this appears to be a unique case that expands the spectrum of neuroendocrine neoplasia of the urinary bladder.

关键词： Laminated glass   Balcony balustrade   Fire spread   Empirical evidence   Fire safety engineering  

摘要： A qualitative assessment of fire hazard posed by laminated glass balcony balustrades was carried out through an in-depth analysis of empirical evidence from six (6) past balcony fires with glass balustrades to deduce the type of glass used and understand the mechanism for fire spread in these fire scenarios. Post-fire conditions of these balconies were studied based on their post-breakage integrity and presence of decolourisation/delamination in order to determine the type of glass used in these balconies. A visual observation of the overall fire spread during the fire and extent of damage post-fire was then carried out to determine whether there was a correlation between the type of glass used and the extent of fire spread. It was found that fire spread was mainly driven by combustible materials around the balcony construction as the fire damage on the balustrades was limited to the area in the vicinity of the combustible materials and the balustrade glass did not contribute to the fire. Given the current regulatory framework in England that limits the use of laminated glass in balcony balustrades from a fire safety perspective despite its architectural benefits and structural safety, this study shows that there is no evidence that the use of laminated glass would constitute a fire hazard when used as glazed balcony balustrading.

关键词： artificial antigen-presenting cells   cancer immunotherapy   intracellular hydrogelation   radical polymerization   T-cell expansion  

摘要： The growing enthusiasm for cancer immunotherapies and adoptive cell therapies has prompted increasing interest in biomaterials development mimicking natural antigen-presenting cells (APCs) for T-cell expansion. In contrast to conventional bottom-up approaches aimed at layering synthetic substrates with T-cell activation cues, transformation of live dendritic cells (DCs) into artificial APCs (aAPCs) is demonstrated herein using a facile and minimally disruptive hydrogelation technique. Through direct intracellular permeation of poly(ethylene glycol) diacrylate (PEG-DA) hydrogel monomer and UV-activated radical polymerization, intracellular hydrogelation is rapidly accomplished on DCs with minimal influence on cellular morphology and surface antigen display, yielding highly robust and modular cell-gel hybrid constructs amenable to peptide antigen exchange, storable by freezing and lyophilization, and functionalizable with cytokine-releasing carriers for T-cell modulation. The DC-derived aAPCs are shown to induce prolonged T-cell expansion and improve anticancer efficacy of adoptive T-cell therapy in mice compared to nonexpanded control T cells, and the gelation technique is further demonstrated to stabilize primary DCs derived from human donors. The work presents a versatile approach for generating a new class of cell-mimicking biomaterials and opens new venues for immunological interrogation and immunoengineering.

关键词： Acinic cell carcinoma   Mandible   Salivary gland tumor   Head and neck  

摘要： Introduction and importance: Acinic cell carcinoma (ACC) is a rare low-grade salivary gland malignancy that accounts for approximately 17% of all salivary gland malignancies. The most common site affected by ACC is the parotid gland followed by the submandibular glands, minor salivary glands, and sublingual glands. Also, it could hardly be observed in unusual sites such as the jaw bones. Case presentation: This case is an example of a central acinic cell carcinoma in a 73-year-old man who came up with a painless gradual swelling for 15 months. Based on clinico-radio-pathologic findings, the diagnosis of a solid variant Intraosseous Acinic Cell Carcinoma was established. Subsequently, the patient underwent hemimandibulectomy and modified radical neck dissection, followed by postoperative radiotherapy. Within a sixmonth follow-up period, no evidence of residual tumor was found. Clinical discussion: Central salivary gland carcinoma is a rare entity and intraosseous ACC is more scarcely observed. Based on our findings, a total of 17 cases of primary intraosseous ACC have been reported so far. Etiology and clinical presentations of this tumor are still vague due to its rarity. Conclusion: Dentists and oral surgeons must be aware of such a rare malignant lesion when encountering a radiolucent lesion within the jaws. The early diagnosis and a complete surgical excision to achieve tumor-free surgical margins and a long-term follow-up could result in significantly improved survival rates.

关键词： Brain tumors   Glioma   Glioblastoma   Store-operated Ca2+ entry   Purinergic signalling  

摘要： Brain tumors comprise a large series of tumor cancer from benign to highly malignant gliomas and metastases from primary tumors outside the brain. Intracellular Ca2+ homeostasis is involved in a large series of cell functions including cell proliferation, migration, and cell death. Store-operated Ca2+ entry (SOCE), the most important Ca2+ entry pathway in non-excitable cells, is involved in cell proliferation and migration and enhanced in tumor cells from breast cancer, colon cancer and cell lines derived from glioblastoma but there are almost no studies in human primary glioblastoma cells or other brain tumors. We have developed a single procedure to obtain primary cells from a large series (n = 49) of human brain tumors including schwannomas, meningiomas, oligodendrogliomas, astrocytomas, glioblastomas and brain metastases from ovary, breast and lung. Cells were characterized by immunofluorescence and subjected to Ca2+ imaging to investigate resting intracellular Ca2+ levels, Ca2+ responses to physiological agonists as well as voltage-operated Ca2+ entry and SOCE. We found significant differences in resting intracellular Ca2+ and Ca2+ responses to plasma membrane depolarization and ATP among the different tumor cells. Only malignant tumor cells, displayed Ca2+ responses to ATP. SOCE is significantly increased in malignant gliomas whereas voltage-gated Ca2+ entry is decreased. In addition, SOCE is significantly larger in high grade gliomas than in low grade gliomas suggesting that SOCE increases with glioma progression. These data may provide new insights on the role of intracellular Ca2+ and purinergic signalling in brain tumors.

关键词： Nelarabine   T cell acute lymphoblastic leukemia   Refractory disease   Allogeneic stem cell transplantation  

摘要： A significant proportion of T cell acute lymphoblastic leukemia (T-ALL) patients do not achieve complete remission after 4 weeks of induction chemotherapy or relapse early. Salvage chemotherapy for such patients usually results in poor outcome which can be up to 20-30% survival with allogeneic BMT. Nelarabine combined with chemotherapy, in COG AALL0434 study, showed 4-year disease-free survival of 54.8% in patients with primary refractory T ALL. An allogeneic BMT in such patients may further improve outcome. In this report, three patients with primary refractory T cell ALL including a case of ETP-ALL and near ETP-ALL were treated with Nelarabine combined with COG based regime and thereafter an allogeneic stem cell transplantation. All three patients achieved a complete remission with negative minimal residual disease status with one course of therapy, received allo SCT (MSD = 2, Haplo = 1) and are surviving in complete remission at 12 months, 14 months and 25 months of follow up. This report highlights that primary refractory T ALL patient can be successfully treated with Nelarabine in combination with chemotherapy and consolidation with allogeneic SCT to provide maximum chances of long-term survival and cure.

关键词： database research   glycaemic control   insulin therapy   type 2 diabetes  

摘要： Aims To investigate the interrelations between glycaemic metrics of fasting plasma glucose (FPG), postprandial glucose (PPG), glycated haemoglobin (HbA1c), and percentage of time in target range 3.9 to 10.0 mmol/L (%TIR) in patients on insulin therapy. Materials and methods A pooled analysis was conducted using datasets extracted from an integrated database of insulin lispro clinical trials (Eli Lilly and Company). Studies in patients with type 2 diabetes on basal-bolus or basal-plus insulin therapy, and with >= 7-point self-monitored blood glucose profiles were included in the analysis. A multivariate regression model was used to quantify the contribution of FPG and PPG change to the change in HbA1c and %TIR. In addition, a linear regression model was used to describe the relationship between %TIR and HbA1c. Results Five studies encompassing 1572 patients met the criteria for inclusion. On average, a 1-mmol/L change in FPG was associated with 2.7 mmol/mol (0.25%) change in HbA1c (range 2.0 to 2.8 mmol/mol [0.18%-0.26%];all P <0.0001), and a 1-mmol/L change in PPG with 1.8 mmol/mol (0.16%) change in HbA1c (range 1.2 to 2.1 mmol/mol [0.11%-0.19%];all P <0.01). Furthermore, a 1-mmol/L reduction in FPG and PPG was associated with an increase in TIR of 6.5% (range 5.8%-9.2%) and 5.3% (range 4.1%-8.7%), respectively, all P <0.0001. A decrease in HbA1c of 10.9 mmol/mol (1%) corresponded with an increase in TIR of 8.3%, on average. Conclusions In patients with type 2 diabetes on basal-bolus or basal-plus insulin therapy, management of both FPG and PPG is important for achievement of HbA1c and TIR goals.

关键词： Hepatocellular carcinoma (HCC)   Mesenchymal circulating tumor cell (mCTC)   Postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE)   Recurrence-free survival (RFS)   Overall survival (OS)  

摘要： Background We demonstrated that postoperative mesenchymal circulating tumor cell (mCTC) in peripheral blood were independent risk factors for the recurrence of hepatocellular carcinoma (HCC) after radical resection. However, few studies have been conducted on the efficacy and survival benefit of postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) for patients with mCTC-positive HCC. We evaluated the effect of PA-TACE on the prognosis of mCTC-positive/mCTC-negative HCC patients. Methods A total of 261 HCC patients from February 2014 to December 2017 undergoing curative hepatectomy were included in this study. Recurrence-free survival (RFS) rates, overall survival (OS) rates, and prognostic factors were analyzed using the Kaplan-Meier method, log-rank test, and Cox proportional hazard model. Results The results showed that 57.8% (59/102) mCTC-positive and 43.4% (69/159) mCTC-negative patients underwent PA-TACE. Multivariate analyses demonstrated that PVTT (HR 2.370;95% CI, 1.535-3.660;P < 0.001), BCLC stage (B+C) (HR 3.871;95% CI, 2.544-5.892;P < 0.001), mCTC (HR 1.414;95% CI, 1.276-1.622;P < 0.001), and without PA-TACE (HR 1.724;95% CI, 1.152-2.580;P = 0.008) were independent risk factors for poor RFS. Meanwhile, PVTT (HR 1.744;95% CI, 1.261-2.412;P = 0.001), multinodularity (HR 1.416;95% CI, 1.069-1.876;P = 0.015), mCTC (HR 1.612;95% CI, 1.471-1.796;P < 0.001), and without PA-TACE (HR 1.311;95% CI, 1.010-1.701;P = 0.042) were independent risk factors for poor OS. Both RFS (P = 0.004) and OS (P = 0.045) in mCTC-positive patients who received PA-TACE were significantly improved relative to those who underwent hepatic resection alone. Among 102 mCTC-positive patients, the mCTC-positive rate was significantly lower in patients treated with PA-TACE than in those treated with liver resection alone (46.4% vs. 88.4%,P = 0.031). No differences were observed in DFS and OS among the mCTC-negative patients with or without PA-TACE. Early recurrence was more