Our goal is to test whether CS1 could be targeted by chimeric antigen receptor (CAR) T cells treat multiple myeloma (MM).We generated a retroviral construct of CS1-specific CAR and engineered primary human expressing the CAR. We then tested capacity CS1-CAR eradicate MM tumor in vitro, ex vivo, vivo using orthotopic xenograft mouse models.In compared with mock-transduced cells, upon recognizing CS1-positive CS1-CAR-transduced secreted more IFN-γ as well interleukin (IL)-2, expressed higher...

Histone ubiquitination plays a vital role in DNA damage response (DDR), which is important for maintaining genomic integrity eukaryotic cells. In DDR, of histone H2A and γH2AX by the concerted action ubiquitin (Ub) ligases, RNF168 RNF8, generates cascade signaling. However, little known about deubiquitinating enzymes (DUBs) that may catalyze removal Ub from these histones. This study demonstrated USP3, an apparent DUB mono-ubiquitinated H2A, indeed enzyme conjugates lysine sites, where...

Accessibility within chromatin is an important factor in the prompt removal of UV-induced DNA damage by nucleotide excision repair (NER). Chromatin remodeling SWI/SNF complex has been shown to play modulating role NER vitro and yeast vivo. Nevertheless, molecular basis cross-talk between mammalian cells not fully understood. Here, we show that knockdown Brg1, ATPase subunit SWI/SNF, negatively affects elimination cyclobutane pyrimidine dimers (CPD), but (6, 4)pyrimidone photoproducts (6-4PP)...

Abstract Oncolytic viruses, including oncolytic herpes simplex virus (oHSV), have produced provocative therapeutic responses in patients with glioblastoma, the most aggressive brain tumor. Paradoxically, innate immune mediated by natural killer (NK) cells and macrophages/microglia appear to limit oHSV efficacy. Therefore, we investigated whether pretreatment an immunosuppressive cytokine, TGFβ, might reverse these effects thereby potentiate TGFβ treatment of NK rendered them less cytolytic...

Rationale: The mitogen-activated protein kinase pathway (MAPK) is one of the major cancer-driving pathways found in non-small cell lung cancer (NSCLC) patients. ERK inhibitors (ERKi) have been shown to be effective NSCLC patients with MAPK mutations. However, like other inhibitors, ERKi rarely confers complete and durable responses. mechanism tumor relapse after treatment yet defined. Methods: To best study inhibitor patients, we treated various lines patient-derived xenograft (PDX)...

Cancer stem cells (CSCs) represent the root of many solid tumors including ovarian cancer. Eradication CSCs represents a novel cancer therapeutic strategy. Calcitriol, also known as 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], is an active metabolite vitamin D, functioning potent steroid hormone. Calcitriol has shown anti-tumor effects in various cancers by regulating multiple signaling pathways. It been reported that calcitriol can regulate properties normal and CSCs. However, effect on growth...

Autophagy is an intracellular catabolic system. It delivers cellular components to lysosomes for degradation and supplies nutrients that promote cell survival under stress conditions. Although much known regarding starvation-induced autophagy, the regulation of autophagy by energy level less clear. BRUCE ubiquitin conjugase ligase with multi-functionality. has been reported depletion inhibits blockage fusion step. Herein we report a new function in dual energy. Depletion alone (without...

The ovary is the main regulator of female fertility. Granulosa cell dysfunction may be involved in various reproductive endocrine disorders. Here we investigated effect insulin resistance on metabolism and function ovarian granulosa cells, dissected functional status mitogen-activated protein kinase signaling pathway these cells. Our data showed that dexamethasone-induced mouse cells reduced sensitivity, accompanied with an increase phosphorylation p44/42 kinase. Furthermore, up-regulation...

Fusion proteins have unique oncogenic properties and their identification can be useful either as diagnostic or therapeutic targets. Next generation sequencing data previously shown a fusion gene formed between Rad51C ATXN7 genes in the MCF7 breast cancer cell line. However, existence of this colorectal patient tumor tissues is largely still unknown. We evaluated for presence Rad51C-ATXN7 tumors cells by RT-PCR, PCR, Topo TA cloning, Real time immunoprecipitation immunoblotting techniques....

Understanding the mechanisms by which cancer stem cells (CSCs) survive chemotherapy is essential for development of new therapies. Recently, we demonstrated that ovarian CSCs cisplatin treatment through enhanced expression DNA polymerase η (Pol η). Identification micro RNA-93 (miR-93) as regulator Pol provides a novel target to improve outcome platinum-based therapy.

Intrauterine growth restriction (IUGR) can increase the risk of hypertension and kidney disease at adulthood due to fetal programming. In our previous study, we found that supplementation with low concentration ouabain during pregnancy could restore glomerulus numbers birth, rescuing development. However, metabolic pattern in IUGR offspring effect have not been evaluated.In this based on GC-MS LC-MS platforms, used protein rat model explore molecular mechanisms damage induced by protective...

Abstract The Fanconi Anemia (FA) pathway is essential for human cells to maintain genomic integrity following DNA damage. This involved in repairing damaged through homologous recombination. Cancers with a defective FA are expected be more sensitive cross-link based therapy or PARP inhibitors. To evaluate downstream effectors of the pathway, we studied expression 734 different micro RNAs (miRNA) using NanoString nCounter miRNA array two lung cancer and matched control cells, along tumors...

Abstract Ovarian cancer is considered a hormone sensitive tumor. A healthy ovary expresses both Estrogen Receptors alpha (ERα) and beta (ERβ). However, although expression of ERα fairly remains constant, the ERβ gradually decreases as cells undergo malignant transformation furthers with progression cancer. thought to promote genes associated cell survival proliferation enhancing tumor growth. In contrast, ability suppress orthotropic ovarian xenograft development supported role ‘tumor...

Abstract Elevated expression of the anti-apoptotic factor Bcl-2 is believed to be one contributing factors an increased relapse rate associated with multiple cisplatin-resistant cancers. DNA damage-binding protein 2 (DDB2) has recently been revealed play important role in sensitizing human ovarian cancer cells cisplatin-induced apoptosis through down-regulation Bcl-2, but underlying molecular mechanism remains poorly defined. Here, we report that DDB2 functions as a transcriptional repressor...

Abstract Xeroderma pigmentosum group C (XPC) is a DNA repair factor mainly involved in nucleotide excision but also has functions beyond its role repair. More than 60% lung adenocarcinoma patients exhibit XPC copy number deletions, and among these patients, low expression correlated with poor outcome, indicating that may play critical preventing cancer progression. Here, we revealed an inverse relationship between the abundance of stem cell (CSC) subpopulation non-small (NSCLC). We...

Abstract Interferons (IFNs) and Janus Kinase/Signal Transducer Activator of Transcription (JAK/STAT) signaling are best known for their roles in immunity. However, recent work has suggested that both IFNs the JAK/STAT pathways associated with tumor growth progression, as well maintenance cancer stem cell (CSC) populations. To better understand regulation CSC population by IFN/JAK/STAT pathway, we enriched CSCs from a panel non-small lung (NSCLC) lines using spheroid culture determined...

Abstract Cancer stem cells (CSCs), representing the root of many solid tumors including ovarian cancer, have been implicated in disease recurrence, metastasis, and therapeutic resistance. Our previous study has demonstrated that DNA damage-binding protein 2 (DDB2) is able to reduce abundance CSCs bulk cancer cells, providing a novel mechanism explain DDB2-mediated suppression tumorigenicity also suggesting low expression DDB2 required for maintenance CSCs. However, underlying mechanisms...

Abstract Cancer stem cells (CSCs) are considered to play a central role in the cancer progression, metastasis and development of drug resistance. MicroRNAs (miRNAs) have important roles regulating CSC properties be potential therapeutic targets. Diverse aberrantly expressed miRNAs been reported ovarian cells. However, there few reports about that were associated with stemness progression cancer. In this study, miRNA Nanostring profiling analysis was performed screen crucial characteristics...

Abstract Cancer stem cells (CSCs), representing the root of many solid tumors including ovarian cancer, have been implicated in disease recurrence, metastasis, and therapeutic resistance. Our previous study has demonstrated that DNA damage-binding protein 2 (DDB2) is able to reduce abundance CSCs bulk cancer cells, providing a novel mechanism explain DDB2-mediated suppression tumorigenicity also suggesting low expression DDB2 required for maintenance CSCs. However, underlying mechanisms...

Abstract Lung cancer remains a leading cause of cancer-related deaths in the United States with unfavorable prognosis mainly due to tumor relapse and metastasis, which are recently believed be caused by specific population cells within termed “cancer stem (CSCs)”. These share common characteristic self-renewal differentiation as normal cell, but also show resistance chemotherapy radiation therapy. Thus, targeting CSC populations lung tumors is critical prevention metastasis. Xeroderma...

Abstract Many studies have demonstrated the causativeness of cancer stem cells (CSCs), which are able to self-renew, metastasize, differentiate, and resist chemotherapy. Although multiple cell surface markers been used identify isolate cells, their uncertainty makes these unreliable in identifying heterogeneous cells. Some transcription factors shown be overexpressed CSCs residing types cancers, some pathways found regulate CSC populations. However, since do not express all identified genes,...