In situ vaccination: cancer immunotherapy both personalized off-the-shelf
As cancer immunotherapy continues to benefit from novel approaches which cut immune 'brake pedals' (e.g. anti-PD1 and anti-CTLA4 antibodies) and push immune cell gas pedals (e.g. IL2, and IFNα) there will be increasing need to develop immune 'steering wheels' such as vaccines to guide the immune system specifically toward tumor associated antigens. Two primary hurdles in cancer vaccines have been: identification of universal antigens to be used in 'off-the-shelf' vaccines for common cancers, and 2) logistical hurdles of ex vivo production of individualized whole tumor cell vaccines. (Source: Molecular Oncology)
Source: Molecular Oncology - November 6, 2015 Category: Cancer & Oncology Authors: Linda Hammerich, Adam Binder, Joshua D. Brody Tags: Review Source Type: research
CREB-binding protein regulates lung cancer growth by targeting MAPK and CPSF4 signaling pathway
CBP (CREB-binding protein) is a transcriptional co-activator which possesses HAT (histone acetyltransferace) activity and participates in many biological processes, including embryonic development, growth control and homeostasis. However, its roles and the underlying mechanisms in the regulation of carcinogenesis and tumor development remain largely unknown. Here we investigated the molecular mechanisms and potential targets of CBP involved in tumor growth and survival in lung cancer cells. Elevated expression of CBP was detected in lung cancer cells and tumor tissues compared to the normal lung cells and tissues. (Source: Molecular Oncology)
Source: Molecular Oncology - November 5, 2015 Category: Cancer & Oncology Authors: Zhipeng Tang, Wendan Yu, Shilei Zhao, Yao Xiao, Zhenlong Yu, Canhui Yi, Ranran Tang, Yang Xuan, Wenjing Yang, Jiaojiao Hao, Tingting Xu, Qianyi Zhang, Wenlin Huang, Wuguo Deng, Wei Guo Source Type: research
Genome-wide DNA methylation analyses in lung adenocarcinomas: association with , and mutation status, gene expression and prognosis
DNA methylation alterations are early events in tumorigenesis and important in the regulation of gene expression in cancer cells. Lung cancer patients have in general a poor prognosis, and a deeper insight into the epigenetic landscape in lung adenocarcinoma tumors and its prognostic implications is needed. (Source: Molecular Oncology)
Source: Molecular Oncology - November 5, 2015 Category: Cancer & Oncology Authors: Maria Moksnes Bjaanæs, Thomas Fleischer, Ann Rita Halvorsen, Antoine Daunay, Florence Busato, Steinar Solberg, Lars Jørgensen, Elin Kurea, Hege Edvardsena, Anne-Lise Børresen-Dale, Odd Terje Brustugun, Jörg Tost, Vessela Kristensen, Åslaug Helland Source Type: research
Transcription factor activating protein 2 beta (TFAP2B) mediates noradrenergic neuronal differentiation in neuroblastoma
Neuroblastoma is an embryonal pediatric tumor that originates from the developing sympathetic nervous system and shows a broad range of clinical behavior, ranging from fatal progression to differentiation into benign ganglioneuroma. In experimental neuroblastoma systems, retinoic acid (RA) effectively induces neuronal differentiation, and RA treatment has been therefore integrated in current therapies. However, the molecular mechanisms underlying differentiation are still poorly understood. We here investigated the role of transcription factor activating protein 2 beta (TFAP2B), a key factor in sympathetic nervous system d...
Source: Molecular Oncology - November 3, 2015 Category: Cancer & Oncology Authors: Fakhera Ikram, Sandra Ackermann, Yvonne Kahlert, Ruth Volland, Frederik Roels, Anne Engesser, Falk Hertwig, Hayriye Kocak, Barbara Hero, Daniel Dreidax, Kai-Oliver Henrich, Frank Berthold, Peter Nürnberg, Frank Westermann, Matthias Fischer Source Type: research
Differential expression of miRNAs in pancreatobiliary type of periampullary adenocarcinoma and its associated stroma
Periampullary adenocarcinomas can be of two histological subtypes, intestinal or pancreatobiliary. The latter is more frequent and aggressive, and characterized by a prominent desmoplastic stroma, which is tightly related to the biology of the cancer, including its poor response to chemotherapy. Whereas miRNAs are known to regulate various cellular processes and interactions between cells, their exact role in periampullary carcinoma remains to be characterized, especially with respect to the prominent stromal component of pancreatobiliary type cancers. (Source: Molecular Oncology)
Source: Molecular Oncology - November 2, 2015 Category: Cancer & Oncology Authors: V. Sandhu, IM Bowitz Lothe, K.J. Labori, M.L. Skrede, J. Hamfjord, A.M. Dalsgaard, T. Buanes, G. Dube, M.M. Kale, S. Sawant, U. Kulkarni-Kale, A.-L. Børresen-Dale, O.C. Lingjærde, E.H. Kure Source Type: research
The influence of Insulin-like Growth Factor-1-Receptor expression and endocrine treatment on clinical outcome of postmenopausal hormone receptor positive breast cancer patients: A Dutch TEAM substudy analysis
Signaling via the Insulin-like Growth Factor type 1 Receptor (IGF1R) plays a crucial role in cancer development. In breast cancer (BC), IGF1R and estrogen receptor expression are correlated. In this current study we explored the hypothesis that postmenopausal hormone receptor positive (HR+ve) BC patients with high IGF1R tumor expression still have estrogen driven IGF1R stimulated tumor growth when treated with tamoxifen, resulting in detrimental clinical outcome compared to patients treated with exemestane. (Source: Molecular Oncology)
Source: Molecular Oncology - October 31, 2015 Category: Cancer & Oncology Authors: Charla C. Engels, Nienke A. de Glas, Anita Sajet, Esther Bastiaannet, Vincent THBM. Smit, Peter JK. Kuppen, Caroline Seynaeve, Cornelis JH. van de Velde, Gerrit Jan Liefers Source Type: research
Cancer immunotherapy – converting immune failure to clinical response
In 2013, cancer immunotherapy was selected as breakthrough of the year by the journal Science. After decades of disappointment with therapeutic vaccines that were by and large ineffective (Klebanoff et al., 2011; Rosenberg et al., 2004), it is now clear that current immunotherapeutic strategies can cure patients, even when conventional therapy is insufficient. The tide has changed, but why and how? (Source: Molecular Oncology)
Source: Molecular Oncology - October 29, 2015 Category: Cancer & Oncology Authors: Johanna Olweus Tags: Editorial Source Type: research
Tumor-infiltrating lymphocytes for the treatment of metastatic cancer
Over the past few years melanoma incidence has been rising steadily, resulting in an increase in melanoma related mortality. Until recently, therapeutic options for metastatic melanoma were scarce. Chemotherapy and, in some countries, IL-2 were the only registered treatment modalities. In the last five years, treatment with immunotherapy (anti CTLA-4, anti PD-1, or the combination of these antibodies) has shown very promising results and was able to improve survival in patients with metastatic melanoma. (Source: Molecular Oncology)
Source: Molecular Oncology - October 29, 2015 Category: Cancer & Oncology Authors: M.H. Geukes Foppen, M. Donia, I.M. Svane, J.B.A.G. Haanen Source Type: research
Intracellular antigens as targets for antibody based immunotherapy of malignant diseases
This review discusses the potential use of intracellular tumor antigens as targets of antibody-based immunotherapy for the treatment of solid tumors. In addition, it describes the characteristics of the intracellular tumor antigens targeted with antibodies which have been described in the literature and have been identified in the authors’ laboratory. Finally, the mechanism underlying the trafficking of the intracellular tumor antigens to the plasma membrane of tumor cells are reviewed. (Source: Molecular Oncology)
Source: Molecular Oncology - October 29, 2015 Category: Cancer & Oncology Authors: Yangyang Wang, Xinhui Wang, Cristina R. Ferrone, Joseph H. Schwab, Soldano Ferrone Tags: Review Source Type: research
Development of a circulating miRNA assay to monitor tumor burden: From mouse to man
Circulating miRNA stability suggests potential utility of miRNA based biomarkers to monitor tumor burden and/or progression, particularly in cancer types where serial biopsy is impractical. Assessment of miRNA specificity and sensitivity is challenging within the clinical setting. To address this, circulating miRNAs were examined in mice bearing human SCLC tumor xenografts and SCLC patient derived circulating tumor cell explant models (CDX). We identified 49 miRNAs using human TaqMan Low Density Arrays readily detectable in 10 μl tail vein plasma from mice carrying H526 SCLC xenografts that were low or undetectable in no...
Source: Molecular Oncology - October 28, 2015 Category: Cancer & Oncology Authors: Alastair Greystoke, Mahmood Ayub, Dominic G. Rothwell, Dan Morris, Deborah Burt, Cassandra L. Hodgkinson, Christopher J. Morrow, Nigel Smith, Kwaw Aung, Juan Valle, Louise Carter, Fiona Blackhall, Caroline Dive, Ged Brady Source Type: research
An integrated genomic analysis of Tudor domain–containing proteins identifies PHD finger protein 20-like 1 (PHF20L1) as a candidate oncogene in breast cancer
Tudor domain–containing proteins (TDRDs), which recognize and bind to methyl-lysine/arginine residues on histones and non-histone proteins, play critical roles in regulating chromatin architecture, transcription, genomic stability, and RNA metabolism. Dysregulation of several TDRDs have been observed in various types of cancer. However, neither the genomic landscape nor clinical significance of TDRDs in breast cancer has been explored comprehensively. Here, we performed an integrated genomic and transcriptomic analysis of 41 TDRD genes in breast cancer (TCGA and METABRIC datasets) and identified associations among recurr...
Source: Molecular Oncology - October 28, 2015 Category: Cancer & Oncology Authors: Yuanyuan Jiang, Lanxin Liu, Wenqi Shan, Zeng-Quan Yang Source Type: research
Development of a Circulating miRNA Assay to Monitor Tumour Burden: from Mouse to Man
Circulating miRNA stability suggests potential utility of miRNA based biomarkers to monitor tumour burden and/or progression, particularly in cancer types where serial biopsy is impractical. Assessment of miRNA specificity and sensitivity is challenging within the clinical setting. To address this, circulating miRNAs were examined in mice bearing human SCLC tumour xenografts and SCLC patient derived circulating tumour cell explant models (CDX). We identified 49 miRNAs using human Taqman Low Density Arrays readily detectable in 10μl tail vein plasma from mice carrying H526 SCLC xenografts that were low or undetectable in n...
Source: Molecular Oncology - October 28, 2015 Category: Cancer & Oncology Authors: Alastair Greystoke, Mahmood Ayub, Dominic G. Rothwell, Dan Morris, Deborah Burt, Cassandra L. Hodgkinson, Christopher J. Morrow, Nigel Smith, Kwaw Aung, Juan Valle, Louise Carter, Fiona Blackhall, Caroline Dive, Ged Brady Source Type: research
Endothelial Robo4 suppresses breast cancer growth and metastasis through regulation of tumor angiogenesis
In this study, we used immune competent Robo4 knockout mouse model to show that endothelial Robo4 is important for suppressing breast cancer growth and metastasis. (Source: Molecular Oncology)
Source: Molecular Oncology - October 28, 2015 Category: Cancer & Oncology Authors: Helong Zhao, Dinesh K. Ahirwar, Steve Oghumu, Tasha Wilkie, Catherine A. Powell, Abhay R. Satoskar, Dean Y. Li, Ramesh K. Ganju Source Type: research
An integrated genomic analysis of Tudor domain-containing proteins identifies PHD finger protein 20-like 1 (PHF20L1) as a candidate oncogene in breast cancer
Tudor domain–containing proteins (TDRDs), which recognize and bind to methyl-lysine/arginine residues on histones and non-histone proteins, play critical roles in regulating chromatin architecture, transcription, genomic stability, and RNA metabolism. Dysregulation of several TDRDs have been observed in various types of cancer. However, neither the genomic landscape nor clinical significance of TDRDs in breast cancer has been explored comprehensively. Here, we performed an integrated genomic and transcriptomic analysis of 41 TDRD genes in breast cancer (TCGA and METABRIC datasets) and identified associations among recurr...
Source: Molecular Oncology - October 28, 2015 Category: Cancer & Oncology Authors: Yuanyuan Jiang, Lanxin Liu, Wenqi Shan, Zeng-Quan Yang Source Type: research
Negative immune checkpoints on T lymphocytes and their relevance to cancer immunotherapy
The term ‘inhibitory checkpoint’ refers to the broad spectrum of co-receptors expressed by T cells that negatively regulate T cell activation thus playing a crucial role in maintaining peripheral self-tolerance. Co-inhibitory receptor ligands are highly expressed by a variety of malignancies allowing evasion of anti-tumour immunity. Recent studies demonstrate that manipulation of these co-inhibitory pathways can remove the immunological brakes that impede endogenous immune responses against tumours. (Source: Molecular Oncology)
Source: Molecular Oncology - October 26, 2015 Category: Cancer & Oncology Authors: Anna Śledzińska, Laurie Menger, Katharina Bergerhoff, Karl S. Peggs, Sergio A. Quezada Tags: Review Source Type: research
