Diagnostic, Prognostic and Therapeutic Value of Gene Signatures

Gene expression studies have revealed diagnostic profiles and upregulation of specific pathways in many solid tumors. Some gene-expression signatures are already used as predictors of relapse in early breast cancer patients. The explosion of new information in gene expression profiling could potentially lead to the development of tailored treatments in many solid tumors. In addition, many studies are ongoing to validate these signatures also in predicting response to hormonal, chemotherapeutic, and targeted agents in breast cancer as well as in other tumors. This book has been carried out with the aim of providing readers a useful and comprehensive resource about the range of applications of microarray technology on oncological diseases. The book is principally addressed to resident and fellow physicians, medical oncologists, molecular biologists, biotechnologists, and those who study oncological diseases. The chapters have been written by leading international researchers on these topics who have prepared their manuscripts according to current literature and field experience with microarray technology

Patterns of injury and violence in Yaoundé Cameroon: an analysis of hospital data.

BackgroundInjuries are quickly becoming a leading cause of death globally, disproportionately affecting sub-Saharan Africa, where reports on the epidemiology of injuries are extremely limited. Reports on the patterns and frequency of injuries are available from Cameroon are also scarce. This study explores the patterns of trauma seen at the emergency ward of the busiest trauma center in Cameroon's capital city.Materials and methodsAdministrative records from January 1, 2007, through December 31, 2007, were retrospectively reviewed; information on age, gender, mechanism of injury, and outcome was abstracted for all trauma patients presenting to the emergency ward. Univariate analysis was performed to assess patterns of injuries in terms of mechanism, date, age, and gender. Bivariate analysis was used to explore potential relationships between demographic variables and mechanism of injury.ResultsA total of 6,234 injured people were seen at the Central Hospital of Yaoundé's emergency ward during the year 2007. Males comprised 71% of those injured, and the mean age of injured patients was 29 years (SD = 14.9). Nearly 60% of the injuries were due to road traffic accidents, 46% of which involved a pedestrian. Intentional injuries were the second most common mechanism of injury (22.5%), 55% of which involved unarmed assault. Patients injured in falls were more likely to be admitted to the hospital (p < 0.001), whereas patients suffering intentional injuries and bites were less likely to be hospitalized (p < 0.001). Males were significantly more likely to be admitted than females (p < 0.001)DiscussionPatterns in terms of age, gender, and mechanism of injury are similar to reports from other countries from the same geographic region, but the magnitude of cases reported is high for a single institution in an African city the size of Yaoundé. As the burden of disease is predicted to increase dramatically in sub-Saharan Africa, immediate efforts in prevention and treatment in Cameroon are strongly warranted

Inflammation- and Cancer-Associated Neurolymphatic Remodeling and Cachexia in Pancreatic Ductal Adenocarcinoma

This work addresses two understudied elements of inflammation and malignancy—namely, (1) neurolymphatic remodeling during transitions in microenvironmental inflammatory status and (2) the systemic paraneoplastic inflammatory syndrome cancer-associated cachexia in the context of pancreatic adenocarcinoma (PDAC). Lymphatic vessels undergo dramatic phenotypic changes in initial inflammation, wound recovery, and recurrent inflammation. We identified complementary novel neuroremodeling behaviors under these conditions and hypothesized that both nerve and lymphatic remodeling were directed by a tissue remodeling factor with overlapping functions. We found that nerve growth factor (NGF) influenced not only nerves but also lymphatics. NGF stimulated lymphangiogenesis, inhibited lymphatic vessel regression during wound recovery, and increased nociception. NGF induced VEGF-C protein expression, and ablation of VEGFR-2/3 signaling abrogated NGF-mediated lymphangiogenesis, supporting a hierarchical model of NGF-VEGF signaling with NGF functioning upstream of the VEGF family. We next studied neurolymphatic remodeling in the context of malignancy using a novel murine live imaging platform. Lyve1CreERT2tdT mice inducibly express tdTomato fluorescent protein in Lyve-1+ cells. We implanted fluorescently-labeled tumor cells into cornea and pinna and identified tumor-specific neurolymphatic architecture signatures that are distinct from those associated with nonmalignant inflammation, including disorganized hypersprouting nascent lymphatic vessels and a shift in nerve morphology to a phenotype previously associated only with wound recovery. We also found that manipulating the timing of establishment of inflammation affected tumor cell persistence in tissue. In the final portion of this work, we studied cancer-associated inflammation in a broader context—i.e. the paraneoplastic syndrome cancer-associated cachexia. We sought to address discrepancies in the literature regarding cachexia gene expression with a unique set of PDAC skeletal muscle samples harvested at rapid autopsy and stratified based on severity of cachexia. We found differential expression of a number of candidate targets in PDAC samples compared to cancer-free controls including FAP-α, CAMKIIβ, FBXO32, TIE-1, and TRIM63 and challenged some previous findings. In summary, we defined a novel role for NGF signaling in lymphatics, identified microenvironment-specific neurolymphatic architecture signatures, and highlighted the complexity of cancer-associated cachexia while providing new data about this syndrome in the context of PDAC

Key biological processes driving metastatic spread of pancreatic cancer as identified by multi-omics studies.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy, characterized by a high metastatic burden, already at the time of diagnosis. The metastatic potential of PDAC is one of the main reasons for the poor outcome next to lack of significant improvement in effective treatments in the last decade. Key mutated driver genes, such as activating KRAS mutations, are concordantly expressed in primary and metastatic tumors. However, the biology behind the metastatic potential of PDAC is not fully understood. Recently, large-scale omic approaches have revealed new mechanisms by which PDAC cells gain their metastatic potency. In particular, genomic studies have shown that multiple heterogeneous subclones reside in the primary tumor with different metastatic potential. The development of metastases may be correlated to a more mesenchymal transcriptomic subtype. However, for cancer cells to survive in a distant organ, metastatic sites need to be modulated into pre-metastatic niches. Proteomic studies identified the influence of exosomes on the Kuppfer cells in the liver, which could function to prepare this tissue for metastatic colonization. Phosphoproteomics adds an extra layer to the established omic techniques by unravelling key functional signaling. Future studies integrating results from these large-scale omic approaches will hopefully improve PDAC prognosis through identification of new therapeutic targets and patient selection tools. In this article, we will review the current knowledge on the biology of PDAC metastasis unravelled by large scale multi-omic approaches

Radiomics applications in gastrointestinal oncology: the colorectal cancer model

Colorectal cancer (CRC) represents the third most common diagnosis of cancer in the worldwide, accounting for around 10% of all new cancer cases globally. Prognosis of patients affected by CRC is strongly dependent on the stage at diagnosis. Besides epidemiologic data, CRC is a complex and heterogeneous disease with different molecular, genetic and epi-genetic sub-types that led to different scenario in the disease course. As a consequence of heterogeneity, tissue sampling biopsy at diagnosis cannot be considered fully representative of tumor behavior and molecular profile. In this context a complete risk stratification to set the best personalized treatment is very important to reduce the risk of recurrence and improve survival. Medical imaging plays a pivotal role in all aspects of personalized medicine: prediction, diagnosis and especially treatment planning, in the choice of the best treatment for the specific patient at the right time. Among the most promising imaging techniques with the potential to improve cancer treatment and outcome, one cannot but include Radiomics. Radiomics is a methodology of advanced quantitative image analysis which uses mathematical algorithms to extract characteristic features from clinical imaging data. Prior studies have evaluated the use of radiomics analysis in CT imaging for adding information about cancer aggressiveness as well as for predicting treatment response. In the colon cancer staging, CT represent the main clinical imaging method to stage the tumor and manage the therapy choices. The major goal of CT is to determine by visual assessment if there is direct invasion of adjacent organs, presence of pathologic lymph nodes and, evidence of distant metastases. Radiomics in colon cancer is proposed to potentially improve characterization and prognosis, mostly using Computed Tomography (CT). The aim of the present thesis is to assess the role of CT imaging-based Radiomics in the colon cancer evaluation at staging to improve disease risk stratification in terms of tumor aggressiveness and lymph node metastasis to manage the best therapeutic approach tailored for the patient at clinical staging

A systematic review of prostate cancer heterogeneity: understanding the clonal ancestry of multifocal disease

Context Studies characterising genomic changes in prostate cancer (PCa) during natural progression have greatly increased our understanding of the disease. A better understanding of the evolutionary history of PCa would allow advances in diagnostics, prognostication, and novel therapies that together will improve patient outcomes. Objective To review the molecular heterogeneity of PCa and assess recent efforts to profile intratumoural heterogeneity and clonal evolution. Evidence acquisition We screened a total of 1313 abstracts from PubMed published between 2009 and 2020, of which we reviewed 84 full-text articles. We excluded 49, resulting in 35 studies for qualitative analysis. Evidence synthesis In studies of primary disease (16 studies, 4793 specimens), there is a lack of consensus regarding the monoclonal or polyclonal origin of primary PCa. There is no consistent mutation giving rise to primary PCa. Detailed clonal analysis of primary PCa has been limited by current techniques. By contrast, clonal relationships between PCa metastases and a potentiating clone have been consistently identified (19 studies, 732 specimens). Metastatic specimens demonstrate consistent truncal genomic aberrations that suggest monoclonal metastatic progenitors. Conclusions The relationship between the clonal dynamics of PCa and clinical outcomes needs further investigation. It is likely that this will provide a biological rationale for whether radical treatment of the primary tumour benefits patients with oligometastatic PCa. Future studies on the mutational burden in primary disease at single-cell resolution should permit the identification of clonal patterns underpinning the origin of lethal PCa. Patient summary Prostate cancers arise in different parts of the prostate because of DNA mutations that occur by chance at different times. These cancer cells and their origin can be tracked by DNA mapping. In this review we summarise the state of the art and outline what further science is needed to provide the missing answers