Sanforddickens8621
Glioblastomas (GBM) are the most frequent and aggressive human brain tumors due to their high capacity to migrate, invade healthy brain tissue, and resist anticancer therapies. It has been reported that testosterone (T) levels are higher in patients with GBM than in healthy controls. It has also been demonstrated that T induces proliferation, migration, and invasion of human GBM cell lines. T is mainly metabolized to 5α-dihydrotestosterone (DHT) by the enzyme 5α-reductase (5αR), but the role of this metabolite in GBM cells is unknown.
The expression of 5αR isoenzymes and
in biopsies of GBMs was determined by the analysis of TCGA. U87 and U251 GBM cell lines were grown in supplemented DMEM. For evaluating the expression of
in U251 and U87 cells, a RT-qPCR was performed. The cells were treated with T, DHT, finasteride (FIN), dutasteride (D), and the combined treatments, FIN+T and D+T or vehicle. After treatments, the viability was quantified by the trypan blue exclusion assay, the proliferation was al structure of DHT, which increases its affinity for AR and decreases five times the rate of dissociation compared to T. Also, it is possible that DHT mediates the effects of T on cell human GBM cells motility by changing the expression of genes involved in tumor infiltration.
The development and metastasis of cancer cells are regulated by tumor-associated macrophages (TAMs) present in the surrounding tumor microenvironment. RIG-I is a key pathogen recognition receptor against RNA viruses that regulates innate immunity in cancer progression. Till now, the mechanism of RIG-I regulation of the polarization of TAMs in the progression of hepatocellular carcinoma (HCC) has not been understood.
Levels of RIG-I and the key proteins in the NF-κB pathway in HCC and paired paracancerous tissues were detected by Western blotting. The transfection efficiency of RIG-I was observed by fluorescence microscopy. The M1 and M2 markers were detected by real-time polymerase chain reaction and FACS assays. Apoptosis of RIG-I lentivirus-infected HCC cells was detected by flow cytometry assay. Death of Hepa1-6 and H22 cells was analyzed by lactate dehydrogenase releasing assay.
The level of RIG-I was decreased in HCC tissues as compared to that in the paired paracancerous tissues. Overexpression ofapy of HCC.
Our results demonstrate that overexpression of RIG-I promoted apoptosis and death of HCC cells. Moreover, RIG-I promoted the polarization of M1 through the RIG-I/MAVS/TRAF2/NF-κB pathway in mice peritoneal macrophages, suggesting that RIG-I may be a novel target in the immunotherapy of HCC.
Thomsen-Friedenreich antibody (TF-Ab) is a specific antibody against the Thomsen-Friedenreich antigen (TF-Ag). At present, studies on a number of other tumors have shown that TF-Ab can effectively inhibit metastasis and induce apoptosis in tumor cells. However, the role of TF-Ab in thyroid cancer (TC) remains unclear.
Normal subjects and patients with primary papillary TC with or without lymph node metastasis were tested for TF-Ab expression by enzyme-linked immunosorbent assays (ELISAs). Immunofluorescence was used to assess the expression of TF-Ag in thyroid papillary carcinoma with or without lymph node metastasis and undifferentiated cancer tissues. To evaluate the role of TF-Ab in TC, the effects of TF monoclonal antibody (mAb A78-G/A7) on cell biological function were investigated by MTT assays, flow cytometry, adhesion assays and transwell experiments.
Compared with normal individuals, TF-Ab levels in patients with TC were decreased, but no changes were observed with respect to lymph node metastasis. The expression of TF-Ag in TC tissues was relatively higher than that detected in adjacent tissues, but it was not affected by the presence or absence of lymph node metastasis. Upon treatment mAb A78-G/A7 treating, TC cell cycles were affected, meanwhile the abilities to adhere, invade and migrate were also significantly reduced.
The results of the present study showed that mAb A78-G/A7 could affect the invasion and migration of all assayed TC cell lines. The effects of mAb A78-G/A7 on the cell cycle, adhesion, invasion and migration of TC cells were more significant than those observed for proliferation and apoptosis.
The results of the present study showed that mAb A78-G/A7 could affect the invasion and migration of all assayed TC cell lines. The effects of mAb A78-G/A7 on the cell cycle, adhesion, invasion and migration of TC cells were more significant than those observed for proliferation and apoptosis.Generations of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) can significantly improve the outcome of EGFR-positive NSCLC patients. However, acquired TKIs-resistant mutations are inevitable. Except the common EGFR alterations, more and more rare mutations are revealed by next-generation sequencing (NGS), the clinical significance of which are still unclear. Here, we report an advanced lung adenocarcinoma patient who harbored two novel EGFR exon 19 deletions (750_758del and I759S) at the beginning and exhibited a short response to icotinib for 7.0 months. Then, secondary resistance EGFR T751_I759delinsS occurred. Chemotherapy combined with bevacizumab and erlotinib was administered in turn but failed. Standard-dose osimertinib (80 mg daily) obtained durable clinical remission for 16 months, and high-dose osimertinib (160 mg daily) further prolonged the survival of 9 months after leptomeningeal metastases (LM) occurring. This study presented the first case of intractable terminal NSCLC in a patient with EGFR 750_758del, I759S and T751_I759delinsS mutations, who responded positively to osimertinib and achieved a prolonged OS of 52 months, providing a potential therapeutic option for the patients harboring these particular EGFR mutations.
Acute myeloid leukemia (AML) is a group of malignant hematopoietic system diseases. Taurine-upregulated gene 1 (TUG1) is a long non-coding RNA that has been associated with human cancers, including AML. However, the role and molecular mechanisms of TUG1 in AML remains to be defined.
Expression of TUG1 and miR-185 was detected using RT-qPCR. EN450 Cell viability and apoptotic rate were measured by MTT assay and flow cytometry, respectively. Glycolysis was determined by commercial glucose and lactate assay kits and Western blot. The target binding between TUG1 and miR-185 was predicted on Starbase online database and confirmed by luciferase reporter assay and RNA immunoprecipitation.
TUG1 was upregulated and miR-185 was downregulated in the peripheral blood mononuclear cells of AML specimens and cells (HL-60, KG-1, MOLM-14, and MOLM-13). Both TUG1 knockdown and miR-185 overexpression via transfection could suppress cell viability, glucose consumption, lactate production, and hexokinase 2 expression, but promote apoptotic rate in HL-60 and KG-1 cells.
