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Steven L. Wood

Bio: Steven L. Wood is an academic researcher from University of Sheffield. The author has contributed to research in topics: Bone metastasis & Metastasis. The author has an hindex of 13, co-authored 29 publications receiving 871 citations. Previous affiliations of Steven L. Wood include University of Manchester & Manchester Academic Health Science Centre.

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TL;DR: The role of cell-cell interactions, ECM remodeling and autocrine/paracrine signaling interactions between tumor cells and the surrounding stroma is discussed, and the mechanistic basis of lung cancer metastasis to specific organs is also described.

322 citations

Journal ArticleDOI
TL;DR: An assessment of molecular profiling within lung cancer concerning molecular mechanisms, treatment options and disease-progression is provided and future challenges for lung cancer treatment addressed such as detection of micro-metastases and cancer stem cells.

144 citations

Journal ArticleDOI
TL;DR: The composite biomarker, macrophage-capping protein (CAPG and GIPC1 in primary breast tumors, predicted disease outcomes and benefit from zoledronate and may facilitate patient selection for adjuvant bisphosphonate treatment.
Abstract: Background: Bone is the predominant site of metastasis from breast cancer, and recent trials have demonstrated that adjuvant bisphosphonate therapy can reduce bone metastasis development and improve survival. There is an unmet need for prognostic and predictive biomarkers so that therapy can be appropriately targeted. Methods: Potential biomarkers for bone metastasis were identified using proteomic comparison of bone-metastatic, lungmetastatic, and nonmetastatic variants of human breast cancer MDA-MB-231 cells. Clinical validation was performed using immunohistochemical staining of tumor tissue microarrays from patients in a large randomized trial of adjuvant zoledronic acid (zoledronate) (AZURE-ISRCTN79831382). We used Cox proportional hazards regression, the Kaplan-Meier estimate of the survival function, and the log-rank test to investigate associations between protein expression, clinical variables, and time to distant recurrence events. All statistical tests were two-sided. Results: Two novel biomarker candidates, macrophage-capping protein (CAPG) and PDZ domain-containing protein GIPC1 (GIPC1), were identified for clinical validation. Cox regression analysis of AZURE training and validation sets showed that control patients (no zoledronate) were more likely to develop first distant recurrence in bone (hazard ratio [HR] = 4.5, 95% confidence interval [CI] = 2.1 to 9.8, P < .001) and die (HR for overall survival = 1.8, 95% CI = 1.01 to 3.24, P = .045) if both proteins were highly expressed in the primary tumor. In patients with high expression of both proteins, zoledronate had a substantial effect, leading to 10-fold hazard ratio reduction (compared with control) for first distant recurrence in bone (P = .008). Conclusions: The composite biomarker, CAPG and GIPC1 in primary breast tumors, predicted disease outcomes and benefit from zoledronate and may facilitate patient selection for adjuvant bisphosphonate treatment.

77 citations

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TL;DR: The development of robust, easy-to-use clinical tests based on novel biomarkers has the potential to impact upon diagnosis, prognosis and monitoring and could revolutionize the treatment and management of urological cancers.
Abstract: Urine is an ideal body fluid for the detection of protein markers produced by urological cancers as it can be sampled noninvasively and contains secreted and directly shed proteins from the prostate, bladder and kidney. Major challenges of working with urine include high inter-individual and intra-individual variability, low protein concentration, the presence of salts and the dynamic range of protein expression. Despite these challenges, significant progress is being made using modern proteomic methods to identify and characterize protein-based markers for urological cancers. The development of robust, easy-to-use clinical tests based on novel biomarkers has the potential to impact upon diagnosis, prognosis and monitoring and could revolutionize the treatment and management of these cancers.

76 citations

Journal ArticleDOI
TL;DR: The results illustrate the potential of immunodepletion followed by 1‐D nano‐LC‐LTQ Orbitrap Velos analysis in a moderate through‐put biomarker discovery process.
Abstract: Immunodepletion of clinical fluids to overcome the dominance by a few very abundant proteins has been explored but studies are few, commonly examining only limited aspects with one analytical platform. We have systematically compared immunodepletion of 6, 14, or 20 proteins using serum from renal transplant patients, analysing reproducibility, depth of coverage, efficiency, and specificity using 2-D DIGE (‘top-down’) and LC-MS/MS (‘bottom-up’). A progressive increase in protein number (≥2 unique peptides) was found from 159 in unfractionated serum to 301 following 20 protein depletion using a relatively high-throughput 1-D-LC-MS/MS approach, including known biomarkers and moderate–lower abundance proteins such as NGAL and cytokine/growth factor receptors. On the contrary, readout by 2-D DIGE demonstrated good reproducibility of immunodepletion, but additional proteins seen tended to be isoforms of existing proteins. Depletion of 14 or 20 proteins followed by LC-MS/MS showed excellent reproducibility of proteins detected and a significant overlap between columns. Using label-free analysis, greater run-to-run variability was seen with the Prot20 column compared with the MARS14 column (median %CVs of 30.9 versus 18.2%, respectively) and a corresponding wider precision profile for the Prot20. These results illustrate the potential of immunodepletion followed by 1-D nano-LC-LTQ Orbitrap Velos analysis in a moderate through-put biomarker discovery process.

68 citations


Cited by
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Journal ArticleDOI
TL;DR: PSA is more sensitive than PAP in the detection of prostatic cancer and will probably be more useful in monitoring responses and recurrence after therapy, however, since both PSA and PAP may be elevated in benign prostatic hyperplasia, neither marker is specific.

722 citations

Journal ArticleDOI
TL;DR: The biochemical events and parameters involved in the metastatic process and tumor microenvironment have been targeted or can be potential targets for metastasis prevention and inhibition and this review provides an overview of them.

640 citations

Journal ArticleDOI
TL;DR: Assessment of metastatic spread in colon and rectal cancers using a population based approach revealed Thoracic metastases are almost as common as liver metastases in rectal cancer patients with a low stage at diagnosis and should help clinicians to identify patients in need for extra surveillance.
Abstract: Investigating epidemiology of metastatic colon and rectal cancer is challenging, because cancer registries seldom record metastatic sites. We used a population based approach to assess metastatic spread in colon and rectal cancers. 49,096 patients with colorectal cancer were identified from the nationwide Swedish Cancer Registry. Metastatic sites were identified from the National Patient Register and Cause of Death Register. Rectal cancer more frequently metastasized into thoracic organs (OR = 2.4) and the nervous system (1.5) and less frequently within the peritoneum (0.3). Mucinous and signet ring adenocarcinomas more frequently metastasized within the peritoneum compared with generic adenocarcinoma (3.8 [colon]/3.2 [rectum]), and less frequently into the liver (0.5/0.6). Lung metastases occurred frequently together with nervous system metastases, whereas peritoneal metastases were often listed with ovarian and pleural metastases. Thoracic metastases are almost as common as liver metastases in rectal cancer patients with a low stage at diagnosis. In colorectal cancer patients with solitary metastases the survival differed between 5 and 19 months depending on T or N stage. Metastatic patterns differ notably between colon and rectal cancers. This knowledge should help clinicians to identify patients in need for extra surveillance and gives insight to further studies on the mechanisms of metastasis.

587 citations

Journal ArticleDOI
TL;DR: How the tumour-reprogrammed lung microenvironment can contribute to primary lung tumour progression as well as lung metastasis from extrapulmonary neoplasms by promoting inflammation, angiogenesis, immune modulation and therapeutic responses is discussed.
Abstract: Lung cancer is a major global health problem, as it is the leading cause of cancer-related deaths worldwide. Major advances in the identification of key mutational alterations have led to the development of molecularly targeted therapies, whose efficacy has been limited by emergence of resistance mechanisms. US Food and Drug Administration (FDA)-approved therapies targeting angiogenesis and more recently immune checkpoints have reinvigorated enthusiasm in elucidating the prognostic and pathophysiological roles of the tumour microenvironment in lung cancer. In this Review, we highlight recent advances and emerging concepts for how the tumour-reprogrammed lung microenvironment promotes both primary lung tumours and lung metastasis from extrapulmonary neoplasms by contributing to inflammation, angiogenesis, immune modulation and response to therapies. We also discuss the potential of understanding tumour microenvironmental processes to identify biomarkers of clinical utility and to develop novel targeted therapies against lung cancer.

552 citations