Editorial Board
(Source: Molecular Oncology)
Source: Molecular Oncology - October 23, 2015 Category: Cancer & Oncology Source Type: research
Allo-reactive T cells for the treatment of hematological malignancies
Several mechanisms can be responsible for control of hematological tumors by allo-reactive T cells. Following allogeneic stem cell transplantation (alloSCT) donor T cells recognizing genetic disparities presented on recipient cells and not on donor cells are main effectors of tumor control, but also of the detrimental graft versus host disease (GVHD). Since after transplantation normal hematopoiesis is of donor origin, any T cell response directed against polymorphic antigens expressed on hematopoietic recipient cells but not on donor cells will result in an anti-tumor response not affecting normal hematopoiesis. (Source: Molecular Oncology)
Source: Molecular Oncology - October 23, 2015 Category: Cancer & Oncology Authors: J.H.F. Falkenburg, I. Jedema Tags: Review Source Type: research
CAR T-cell immunotherapy: The path from the by-road to the freeway?
Chimeric antigen receptors are genetically encoded artificial fusion molecules that can re-program the specificity of peripheral blood polyclonal T-cells against a selected cell surface target. Unparallelled clinical efficacy has recently been demonstrated using this approach to treat patients with refractory B-cell malignancy. However, the approach is technically challenging and can elicit severe toxicity in patients. Moreover, solid tumours have largely proven refractory to this approach. In this review, we describe the important structural features of CARs and how this may influence function. (Source: Molecular Oncology)
Source: Molecular Oncology - October 22, 2015 Category: Cancer & Oncology Authors: Lynsey M. Whilding, John Maher Tags: Review Source Type: research
Cancer Immunotherapy: Strategies for Personalization and Combinatorial Approaches
The results of recent clinical trials using novel immunotherapy strategies such as immune checkpoint blockade and adoptive T-cell therapy approaches including CAR T-cell therapy have clearly established immunotherapy as an important modality for the treatment of cancer besides the traditional approaches of surgery, radiotherapy, and chemotherapy or targeted therapy. However, to date immunotherapy has been shown to induce durable clinical benefit in only a fraction of the patients. The use of combination strategies is likely to increase the number of patients that might benefit from immunotherapy. (Source: Molecular Oncology)
Source: Molecular Oncology - October 22, 2015 Category: Cancer & Oncology Authors: Vishwanath Sathyanarayanan, Sattva S. Neelapu Tags: Review Source Type: research
CAR T-cell immunotherapy: the path from the by-road to the freeway?
Chimeric antigen receptors are genetically encoded artificial fusion molecules that can re-program the specificity of peripheral blood polyclonal T-cells against a selected cell surface target. Unparalleled clinical efficacy has recently been demonstrated using this approach to treat patients with refractory B-cell malignancy. However, the approach is technically challenging and can elicit severe toxicity in patients. Moreover, solid tumours have largely proven refractory to this approach. In this review, we describe the important structural features of CARs and how this may influence function. (Source: Molecular Oncology)
Source: Molecular Oncology - October 22, 2015 Category: Cancer & Oncology Authors: Lynsey M. Whilding, John Maher Source Type: research
T-cell receptor gene therapy – Ready to go viral?
T lymphocytes can be redirected to recognize a tumor target and harnessed to combat cancer by genetic introduction of T-cell receptors of a defined specificity. This approach has recently mediated encouraging clinical responses in patients with cancers previously regarded as incurable. However, despite the great promise, T-cell receptor gene therapy still faces a multitude of obstacles. Identification of epitopes that enable effective targeting of all the cells in a heterogeneous tumor while sparing normal tissues remains perhaps the most demanding challenge. (Source: Molecular Oncology)
Source: Molecular Oncology - October 19, 2015 Category: Cancer & Oncology Authors: Terhi Karpanen, Johanna Olweus Tags: Review Source Type: research
The Canonical Wnt Pathway Regulates the Metastasis-Promoting Mucin MUC4 in Pancreatic Ductal Adenocarcinoma
Aberrant Wnt signaling frequently occurs in pancreatic cancer (PC) and contributes to disease progression/metastases. Likewise, the transmembrane-mucin MUC4 is expressed de novo in early pancreatic intraepithelial neoplasia (PanINs) and incrementally increases with PC progression, contributing to metastasis. To determine the mechanism of MUC4 upregulation in PC, we examined factors deregulated in early PC progression, such as Wnt/β-catenin signaling. MUC4 promoter analysis revealed the presence of three putative TCF/LEF-binding sites, leading us to hypothesize that MUC4 can be regulated by β-catenin. (Source: Molecular Oncology)
Source: Molecular Oncology - October 19, 2015 Category: Cancer & Oncology Authors: Priya Pai, Satyanarayana Rachagani, Imayavaramban Lakshmanan, Muzafar A. Macha, Yuri Sheinin, Lynette M. Smith, Moorthy P. Ponnusamy, Surinder K. Batra Source Type: research
T-cell receptor gene therapy - ready to go viral?
T lymphocytes can be redirected to recognize a tumor target and harnessed to combat cancer by genetic introduction of T-cell receptors of a defined specificity. This approach has recently mediated encouraging clinical responses in patients with cancers previously regarded as incurable. However, despite the great promise, T-cell receptor gene therapy still faces a multitude of obstacles. Identification of epitopes that enable effective targeting of all the cells in a heterogeneous tumor while sparing normal tissues remains perhaps the most demanding challenge. (Source: Molecular Oncology)
Source: Molecular Oncology - October 19, 2015 Category: Cancer & Oncology Authors: Terhi Karpanen, Johanna Olweus Tags: Review Source Type: research
Conversion to stem-cell state in response to microenvironmental cues is regulated by balance between epithelial and mesenchymal features in lung cancer cells
Cancer cells within a tumor are functionally heterogeneous and specific subpopulations, defined as cancer initiating cells (CICs), are endowed with higher tumor forming potential. The CIC state, however, is not hierarchically stable and conversion of non-CICs to CICs under microenvironment signals might represent a determinant of tumor aggressiveness. How plasticity is regulated at the cellular level is however poorly understood. To identify determinants of plasticity in lung cancer we exposed eight different cell lines to TGFβ1 to induce EMT and stimulate modulation of CD133+ CICs. (Source: Molecular Oncology)
Source: Molecular Oncology - October 12, 2015 Category: Cancer & Oncology Authors: Francesca Andriani, Giulia Bertolini, Federica Facchinetti, Erika Baldoli, Massimo Moro, Patrizia Casalini, Roberto Caserini, Massimo Milione, Giorgia Leone, Giuseppe Pelosi, Ugo Pastorino, Gabriella Sozzi, Luca Roz Source Type: research
Predicting prognosis and therapeutic response from interactions between lymphocytes and tumor cells
As epithelial tumors grow from single cells to a malignant mass of invasive tissue, they must exploit the innate inflammatory response, while evading the adaptive immune system. Prognosis of solid tumors has historically focused on macroscopic features such as size, grade, and mitotic index. It is now clear that prognosis assessment must also consider the stromal and immune cells that surround and infiltrate the tumor. Tumors promote growth, angiogenesis, and tissue remodeling by subverting the normal functions of macrophages and other cells of the innate immune system that inhabit their microenvironment. (Source: Molecular Oncology)
Source: Molecular Oncology - October 11, 2015 Category: Cancer & Oncology Authors: David A. Quigley, Vessela Kristensen Source Type: research
Harnessing Adaptive Natural Killer Cells in Cancer Immunotherapy
Natural killer (NK) cells are innate lymphocytes with a refined ability to recognize transformed cells through a broad array of activating receptors in combination with stochastically expressed inhibitory receptors that recognize MHC-class I. Recent advances in NK cell biology have revealed a high degree of functional plasticity that can be attributed to dynamic cell-to-cell interactions in concert with transcriptional and epigenetic reprogramming. Here, we discuss how new insights into the adaptive behavior of NK cells pave the way for next generation cell therapy based on guided differentiation and selective expansion of...
Source: Molecular Oncology - October 10, 2015 Category: Cancer & Oncology Authors: Lisa L. Liu, Aline Pfefferle, Vincent Oei Yi Sheng, Andreas Björklund, Vivien Béziat, Jodie Goodridge, Karl-Johan Malmberg Tags: Review Source Type: research
expression is inversely correlated with amplification or expression and associated with poor survival in non--amplified neuroblastoma
Neuroblastoma (NB) is the most common extra cranial solid tumor in childhood and the most frequently diagnosed neoplasm during infancy. A striking feature of this tumor is its clinical heterogeneity. Several tumor progression markers have been delineated so far, among which MYCN amplification, which occurs in about 25% of total NB cases, with the percentage increasing to 30% in advanced stage NB. Although MYCN amplification is strongly correlated with NB of poor outcome, the MYCN status cannot alone predict all cases of poor survival in NB. (Source: Molecular Oncology)
Source: Molecular Oncology - October 7, 2015 Category: Cancer & Oncology Authors: Caroline Masserot, Qing-Yuan Liu, Eric Nguyen, Charles-Henry Gattolliat, Dominique Valteau-Couanet, Jean Bénard, Catherine Huber, Evelyne Ségal-Bendirdjian Source Type: research
Chk1 phosphorylated at serine is a predictor of early local recurrence and radio-resistance in breast cancer
Radiation-induced DNA damage activates the DNA damage response (DDR). DDR up-regulation may predict radio-resistance and increase the risk of early local recurrence despite radiotherapy in early stage breast cancers. In 1755 early stage breast cancers, DDR signalling [ATM, ATR, total Ckh1, Chk1 phosphorylated at serine345 (pChk1), Chk2, p53], base excision repair [PARP1, POLβ, XRCC1, FEN1, SMUG1], non-homologous end joining (Ku70/Ku80, DNA-PKcs) and homologous recombination [RAD51, BRCA1, γH2AX, BLM, WRN, RECQL5, PTEN] protein expression was correlated to time to early local recurrence. (Source: Molecular Oncology)
Source: Molecular Oncology - October 2, 2015 Category: Cancer & Oncology Authors: Nouf Alsubhi, Fiona Middleton, Tarek M.A. Abdel-Fatah, Peter Stephens, Rachel Doherty, Arvind Arora, Paul M. Moseley, Stephen Y.T. Chan, Mohammed A. Aleskandarany, Andrew R. Green, Emad A. Rakha, Ian O. Ellis, Stewart G. Martin, Nicola J. Curtin, Srinivas Source Type: research
Chk1 phosphorylated at serine is a predictor of early local recurrence and radio-resistance in breast cancer
Radiation-induced DNA damage activates the DNA damage response (DDR). DDR up-regulation may predict radio-resistance and increase the risk of early local recurrence despite radiotherapy in early stage breast cancers. In 1755 early stage breast cancers, DDR signalling [ATM, ATR, total Ckh1, Chk1 phosphorylated at serine 345 (pChk1), Chk2, p53], base excision repair [PARP1, POLβ, XRCC1, FEN1, SMUG1], non-homologous end joining (Ku70/Ku80, DNA-PKcs) and homologous recombination [RAD51, BRCA1, γH2AX, BLM, WRN, RECQL5, PTEN] protein expression was correlated to time to early local recurrence. (Source: Molecular Oncology)
Source: Molecular Oncology - October 2, 2015 Category: Cancer & Oncology Authors: Nouf Alsubhi, Fiona Middleton, Tarek MA. Abdel-Fatah, Peter Stephens, Rachel Doherty, Arvind Arora, Paul M. Moseley, Stephen YT. Chan, Mohammed A. Aleskandarany, Andrew R. Green, Emad A. Rakha, Ian O. Ellis, Stewart G. Martin, Nicola J. Curtin, Srinivasan Source Type: research
5-Hydroxytryptamine promotes hepatocellular carcinoma proliferation by influencing β-catenin
5-Hydroxytryptamine (5-HT), a neurotransmitter and vasoactive factor, has been reported to promote proliferation of serum-deprived hepatocellular carcinoma (HCC) cells but the detailed intracellular mechanism is unknown. As Wnt/β-catenin signalling is highly dysregulated in a majority of HCC, this study explored the regulation of Wnt/β-catenin signalling by 5-HT. The expression of various 5-HT receptors was studied by quantitative real-time polymerase chain reaction (qPCR) in HCC cell lines as well as in 33 pairs of HCC tumour and corresponding adjacent non-tumour tissues. (Source: Molecular Oncology)
Source: Molecular Oncology - September 29, 2015 Category: Cancer & Oncology Authors: Sarwat Fatima, Xiaoki Shi, Zesi Lin, Guo-qing Chen, Xiao-hua Pan, Justin Che–Yuen Wu, John W. Ho, Nikki P. Lee, Hengjun Gao, Ge Zhang, Aiping Lu, Zhao Xiang Bian Source Type: research
