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Cancer Cell & Microenvironment

Lifu Xiao, Zachary D Schultz
Membrane receptors play important roles in regulating cellular activities. Targeting membrane receptors in cancer cells and understanding their interactions with specific ligands are key for cancer prognosis and therapeutics. However, there is a need to develop new technologies to provide molecular insight into ligand-receptor binding chemistry in cell membrane. Integrin receptors are important membrane receptors that regulate cellular migration, invasion and proliferation in tumors. Integrins have a well-known affinity towards small peptide ligands containing arginine-glycine-aspartate (RGD) sequence and are therefore an attractive model system to study ligand-receptor interactions...
2016: Cancer Cell & Microenvironment
Assumpta C Nwaneri, Lucien McBeth, Terry D Hinds
The need for the development of new cancer therapies and push for the design of new targeting techniques is on the rise, and would be useful for cancers that are resistant to current drug treatments. The understanding of the genome has significantly advanced cancer therapy, as well as prevention and earlier detection. This research highlight discusses a potential new type of cancer-targeting molecule, Sweet-P, which is the first of its kind. Sweet-P specifically targets the microRNA-144 binding site in the 3' untranslated region (3' UTR) of the human glucocorticoid receptor β (GRβ), which has been demonstrated to increase expression...
2016: Cancer Cell & Microenvironment
Zhengqi Wang, Kevin D Bunting
A significant role of the microenvironment in leukemogenesis is beginning to emerge. The leukemia cell microenvironment consists of not only the stromal and endothelial cell components but also the normal hematopoietic cells. Signal transducer and activator of transcription 5 (STAT5) is a latent transcription factor that is normally transiently activated by phosphorylation in response to microenvironmental signals. In hematopoietic cells, persistently activated STAT5 via aberrant receptor signaling, Janus kinases (JAKs), or intracellular tyrosine kinases is a bona fide driver of leukemogenesis...
2016: Cancer Cell & Microenvironment
Juan P Cata, Cristina Gutierrez, Reza J Mehran, David Rice, Joseph Nates, Lei Feng, Andrea Rodriguez-Restrepo, Fernando Martinez, Gabriel Mena, Vijaya Gottumukkala
Perioperative and postoperative blood transfusions (BT), anemia and inflammation are associated with poor survivals in patients with non-small cell lung cancer (NSCLC). This study investigated the impact of perioperative BT on the survival of patients with NSCLC taking into account their preoperative inflammatory status and the presence of anemia. Demographic, perioperative, and survival data for 861 patients with stage I NSCLC was collected retrospectively. The primary endpoints of interest were recurrence-free (RFS) and overall survival (OS)...
2016: Cancer Cell & Microenvironment
Chery A Whipple
It was once believed that tumor growth, progression, and metastasis were intrinsically driven by the tumor. Instead, recent research has demonstrated that a solid tumor is surrounded by a complex matrix of cells, particularly fibroblasts, which support and even promote tumor progression. This matrix of stromal cells, also known as the tumor microenvironment (TME), plays a critical role in cancer and may represent a novel therapeutic target. As such, understanding the complex nature of how the tumor initiates and maintains communication, or a "conversation", with the TME is the focus of current investigations...
April 26, 2015: Cancer Cell & Microenvironment
Jessian L Munoz, Vivian Rodriguez-Cruz, Nykia D Walker, Steven J Greco, Pranela Rameshwar
Chemotherapy with Temozolomide (TMZ), radiation and surgery are the primary methods to treat Glioblastoma Multiforme (GBM), the most common adult intracranial tumor with dismal outcome. GBM resistance to therapy is the main reason of poor patient outcomes. Thus, methods to overcome the resistance are an area of extensive research. This highlight focuses on three recently published articles on the mechanism of resistance and possible therapeutic intervention, including RNA treatment with stem cells. We showed a crucial role of the developmental Sonic Hedgehog (SHH) pathway in the acquisition and maintenance of TMZ resistance...
2015: Cancer Cell & Microenvironment
Xuetian Yue, Lihua Wu, Wenwei Hu
Leukemia inhibitory factor (LIF), a secreted cytokine, plays an important role in a wide array of biological processes including inducing differentiation of leukemia cell, inflammatory response, neuronal development, embryonic implantation, stem cell self-renewal and cancer progression, etc. LIF exerts its biological functions mainly through the activation and regulation of JAK/STAT3, AKT, EKR1/2 and mTOR signal pathways. The expression levels of LIF are regulated by many different factors under different conditions in different tissue/cell types...
2015: Cancer Cell & Microenvironment
Yihang Shen, Jun Zhang, Herbert Yu, Peiwen Fei
Fanconi anemia (FA) is a rare human genetic disease, resulting from dysfunction in any of 17 known complementation proteins: FANC-A, B, C, D1, D2, E, F, G, I, J, L, M, N, O, P, Q & S, and other unknowns. Besides the severe bone marrow failure, an extremely high incidence of cancer as well as many other clinic symptoms associated with FA patients, FA cells are known of insufficiency in homologous recombination, DNA mismatch repair, nucleotide excision repair, translesion DNA synthesis, and other molecular defects, leading to genome instability...
2015: Cancer Cell & Microenvironment
Huan Liu, Jin He, Jing Yang
Osteolytic bone destruction is a hallmark of bone-metastatic cancers. Current therapy is unable to completely cure or prevent this disease in patients. The p38 mitogen-activated protein kinase (MAPK) affects a diverse range of intracellular responses with well-known roles in development, cell-cycle and differentiation, inflammation, apoptosis, senescence, and tumorigenesis. This article is an overview of the contribution of tumor cell-expressed p38 MAPK to the regulation of osteoclastogenesis, osteoblastogenesis, and osteolyticbone lesions...
January 1, 2015: Cancer Cell & Microenvironment
Robin K Bishop, Cendy A Valle Oseguera, Juliet V Spencer
Breast cancer is the most common malignancy affecting women worldwide. While a small fraction of breast cancers have a hereditary component, environmental and behavioral factors also impact the development of cancer. Human cytomegalovirus (HCMV) is a member of the Herpesviridae family that is widespread in the general population and has been linked to several forms of cancer. While HCMV DNA has been found in some breast cancer tissue specimens, we wanted to investigate whether a secreted viral cytokine might have an effect on cancerous or even pre-cancerous cells...
2015: Cancer Cell & Microenvironment
Anna R Kwilas, Renee N Donahue, Kwong Y Tsang, James W Hodge
Combination therapy for the treatment of cancer is becoming increasingly essential as we gain improved understanding of the complexity of cancer progression and the mechanisms by which cancer cells become resistant to single-agent therapy. Recent studies, both clinical and preclinical, have suggested that immunotherapy is a promising approach to the treatment of cancer; however, strategies to improve its clinical efficacy are still needed. A number of recent studies have indicated that antiangiogenic tyrosine kinase inhibitors (TKIs) target multiple components of the tumor microenvironment and are an ideal class of agents for synergizing with cancer immunotherapy...
2015: Cancer Cell & Microenvironment
Siqi Chen, Yi Zhang, Timothy M Kuzel, Bin Zhang
Myeloid-derived suppressor cells (MDSCs) are one of the major cell components responsible for cancer immune evasion. Studying mechanisms associated with the regulation of MDSCs is becoming appreciated as another way to manipulate immune responses. MicroRNAs (miRNAs) have been recognized as substances which may interact with MDSCs, and eight miRNAs including miR-17-5p, miR-20a, miR-223, miR-21, miR-155, miR-494, miR-690 and miR-101 are of particular interest regarding MDSC accumulation and function. We have reviewed the data supporting this activity of these entities...
2015: Cancer Cell & Microenvironment
Song Yi Ko, Honami Naora
The lethality of ovarian cancer stems from its propensity to involve the peritoneal cavity. However, the mechanisms that enable ovarian cancer cells to readily adapt to the peritoneal environment are not well understood. Here, we describe our recent studies in which we identified the mechanisms by which the transcription factor encoded by the patterning gene HOXA9 promotes the aggressive behavior of ovarian cancer. Firstly, we identified that HOXA9 promotes ovarian tumor growth and angiogenesis by activating the gene encoding transforming growth factor-β2 (TGF-β2), which in turn stimulates peritoneal fibroblasts and mesenchymal stem cells to acquire features of cancer-associated fibroblasts...
November 13, 2014: Cancer Cell & Microenvironment
Xin Chen, Xianping Shi, Xuejun Wang, Jinbao Liu
Patients with chronic myeloid leukemia (CML) are commonly treated with a specific inhibitor of BCR-ABL tyrosine kinase, imatinib mesylate (IM). Unfortunately, CML patients develop IM-resistance, which has emerged as a significant clinical problem. Somatic mutations, especially T315I mutation, in BCR-ABL kinase domain represent the most common mechanism underlying drug resistance to tyrosine kinase inhibitors (TKI), including imatinib. Thus, it is urgent to develop novel therapeutic strategies to overcome TKI-resistance...
November 1, 2014: Cancer Cell & Microenvironment
Marc Deheeger, Maciej S Lesniak, Atique U Ahmed
The cancer stem cell (CSC) theory is an emerging concept that proposes a hierarchical nature of carcinogenesis, where a small number of tumor cells are capable of driving tumor growth. Despite many unanswered questions surrounding the cancer stem cell model, the hypothesis has rejuvenated hopes for formulating a novel therapeutic strategy for targeting the roots of cancer. This model predicts that cancer stem cells have the capacity to resist conventional radio- and chemotherapy and initiate disease recurrence...
2014: Cancer Cell & Microenvironment
Frank Eckerdt, Stewart Goldman, Leonidas C Platanias
mRNA translation and protein synthesis is an important determinant for cell metabolism and cell homeostasis. Perturbations in cellular homeostasis often result in activation of negative feedback loops as compensatory mechanisms. Although, these mechanisms are important for mammalian cells to adjust to environmental changes, they also pose a major challenge for targeted cancer therapy as they provide escape mechanisms for cancer cells. The mammalian target of rapamycin (mTOR) is a crucial regulator of mRNA translation, protein synthesis and metabolism and represents an attractive target for anticancer therapy...
2014: Cancer Cell & Microenvironment
Pingyu Zhang, Raphael E Pollock
Soft tissue sarcoma is a malignancy that develops from human soft tissues such as muscle, nerve, fat, and blood vessels. The World Health Organization classification comprises about 50 different histologic types of soft tissue sarcoma. Soft tissue sarcoma is treated most often with surgery. Chemotherapy and radiotherapy have shown only minor effects on patient survival in this disease. The overall 5-year survival rate of soft tissue sarcoma is 50%; it has not changed for the past several decades. A new class of therapeutic targets for soft tissue sarcoma was identified recently...
2014: Cancer Cell & Microenvironment
Yajun Liu, Grzegorz Sowa
In addition to cancer cells, primary tumors are composed of a multitude of stromal cell types. Among others, the stromal cell types involved in tumor growth and progression include endothelial cells, fibroblasts, pericytes, stem cells and various cell types of immune origin. While the role of oncogenes or tumor suppressor proteins expressed in cancer cells has been extensively studied, far less is known about potential involvement of proteins expressed in stromal cell types present within the tumor microenvironment...
2014: Cancer Cell & Microenvironment
Jun Wang, Qing Ye, Qing-Bai She
Remarkable progress has been made highlighting the importance of cap-dependent mRNA translation in cancer progression. 4E-BP1 is a translation initiation repressor by sequestering the mRNA cap-binding protein eIF4E and consequently inhibiting the translation of certain key oncogenic mRNAs encoding proteins for cell proliferation, survival, angiogenesis and malignancy. In most tumors, however, the repressive function of 4E-BP1 is compromised by reduction of its expression or phosphorylation mediated by oncogenic signaling pathways...
2014: Cancer Cell & Microenvironment
Tanya Stoyanova, Andrew S Goldstein
The cells that initiate and propagate cancer are important therapeutic targets. However, the progression from cells of origin to tumor-propagating cells is poorly defined for most human cancers. Mouse models indicate that both basal and luminal cells can initiate prostate cancer, while studies with human prostate tissue have demonstrated a role for basal cells in transformation. Our recent study provides evidence that a common cell of origin can produce alternative variants of human epithelial cancer. Our findings also reveal that the cell of origin that initiates cancer is not continuously required to maintain and propagate the disease...
2014: Cancer Cell & Microenvironment
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