Standardised approach to laparoscopic total mesorectal excision for rectal cancer: a prospective multi-centre analysis.

Purpose: Two non-inferiority randomised control trials have questioned the utility of laparoscopic surgery for rectal cancer by failing to prove that pathological markers of high-quality surgery are equivalent to those achieved by open technique. We present short- and long-term post-operative outcomes from the largest single surgeon series of consecutive patients undergoing laparoscopic TME for rectal cancer. We describe the standardised laparoscopic technique developed by the principal surgeon, and the short-term outcomes from three surgeons who were trained in and subsequently adopted the same approach.

Transglutaminase-2 Mediates the Biomechanical Properties of the Colorectal Cancer Tissue Microenvironment that Contribute to Disease Progression.

Colorectal cancer is the third most common cancer worldwide, and the fourth leading cause of malignancy-related mortality. This highlights the need to understand the processes driving this disease in order to develop new treatments and improve patient outcomes. A potential therapeutic target is the increased stiffness of the tumour microenvironment, which is linked to aggressive cancer cell behaviour by enhancing biomechanical signalling.

Novel biomarkers for patient stratification in colorectal cancer: A review of definitions, emerging concepts, and data.

Colorectal cancer (CRC) treatment has become more personalised, incorporating a combination of the individual patient risk assessment, gene testing, and chemotherapy with surgery for optimal care. The improvement of staging with high-resolution imaging has allowed more selective treatments, optimising survival outcomes. The next step is to identify biomarkers that can inform clinicians of expected prognosis and offer the most beneficial treatment, while reducing unnecessary morbidity for the patient.

Long non-coding RNAs within the tumour microenvironment and their role in tumour-stroma cross-talk.

Long non-coding RNAs (lncRNAs) are a diverse class of RNA transcripts which have limited protein coding potential. They perform a variety of cellular functions in health, but have also been implicated during malignant transformation. A further theme in recent years is the critical role of the tumour microenvironment and the dynamic interactions between cancer and stromal cells in promoting invasion and disease progression.

Exosomal microRNAs (exomiRs): Small molecules with a big role in cancer.

Exosomes are secreted vesicles which can transmit molecular cargo between cells. Exosomal microRNAs (exomiRs) have drawn much attention in recent years because there is increasing evidence to suggest that loading of microRNAs into exosomes is not a random process. Preclinical studies have identified functional roles for exomiRs in influencing many hallmarks of cancer.

Exosomal microRNAs derived from colorectal cancer-associated fibroblasts: role in driving cancer progression.

Colorectal cancer is a global disease with increasing incidence. Mortality is largely attributed to metastatic spread and therefore, a mechanistic dissection of the signals which influence tumor progression is needed. Cancer stroma plays a critical role in tumor proliferation, invasion and chemoresistance.

Targeting the Myofibroblastic Cancer-Associated Fibroblast Phenotype Through Inhibition of NOX4.

Background: Cancer-associated fibroblasts (CAFs) are tumor-promoting and correlate with poor survival in many cancers, which has led to their emergence as potential therapeutic targets. However, effective methods to manipulate these cells clinically have yet to be developed.

Methods: CAF accumulation and prognostic significance in head and neck cancer (oral, n = 260; oropharyngeal, n = 271), and colorectal cancer (n = 56) was analyzed using immunohistochemistry.

miR-196b-5p Regulates Colorectal Cancer Cell Migration and Metastases through Interaction with HOXB7 and GALNT5.

miR-196b-5p has been previously implicated in malignant transformation; however, its role in colorectal cancer has not been fully explored. In this study, we examine the clinical and biological relevance of miR-196b-5p, and the molecular pathways regulated by miR-196b-5p in colorectal cancer. miR-196b-5p expression was quantitated by qRT-PCR in 2 independent cohorts composed of 292 patients with colorectal cancer in total, to explore its biomarker potential.

Cellular and viral microRNAs in sepsis: mechanisms of action and clinical applications.

Regardless of its etiology, once septic shock is established, survival rates drop by 7.6% for every hour antibiotic therapy is delayed. The early identification of the cause of infection and prognostic stratification of patients with sepsis are therefore important clinical priorities.

A subset of myofibroblastic cancer-associated fibroblasts regulate collagen fiber elongation, which is prognostic in multiple cancers.

Collagen structure has been shown to influence tumor cell invasion, metastasis and clinical outcome in breast cancer. However, it remains unclear how it affects other solid cancers. Here we utilized multi-photon laser scanning microscopy and Second Harmonic Generation to identify alterations to collagen fiber structure within the tumor stroma of head & neck, esophageal and colorectal cancers.

The clinical significance of fibrinogen plasma levels in patients with diffuse large B cell lymphoma.

Background: Fibrinogen plays a crucial role in the pathophysiology of tumour cell growth, invasion and metastasis. The aim of this study was to evaluate the prognostic significance of pretreatment plasma fibrinogen levels in patients with diffuse large B cell lymphoma (DLBCL) METHODS: Data from 372 patients with DLBCL, diagnosed and treated between 2004 and 2013 at two Austrian centres, were evaluated retrospectively. The prognostic influences of plasma fibrinogen levels and other factors, including age, tumour stage and the National Comprehensive Cancer Network-International Prognostic Index, on 5-year overall survival (OS) and 5-year disease-free survival (DFS) were studied using Kaplan-Meier curves as well as univariate and multivariate Cox regression models.

MicroRNAs in Testicular Cancer Diagnosis and Prognosis.

Testicular cancer processes a unique and clear miRNA expression signature. This differentiates testicular cancer from most other cancer types, which are usually more ambiguous when assigning miRNA patterns. As such, testicular cancer may represent a unique cancer type in which miRNAs find their use as biomarkers for cancer diagnosis and prognosis, with a potential to surpass the current available markers usually with low sensitivity.

Long Non-Coding RNAs in Endometrial Carcinoma.

Endometrial carcinoma (EC), the second most common form of gynaecological malignancy, can be divided into two distinct sub-types: Type I tumours arise from hyperplastic endometrium and typically effect women around the time of menopause, whereas type II tumours arise in postmenopausal women from atrophic endometrium. Long non-coding RNAs (lncRNAs) are a novel class of non-protein coding molecules that have recently been implicated in the pathogenesis of many types of cancer including gynaecological tumours. Although they play critical physiological roles in cellular metabolism, their expression and function are deregulated in EC compared with paired normal tissue, indicating that they may also participate in tumour initiation and progression.

The Clinical Relevance of Long Non-Coding RNAs in Cancer.

Non-coding RNAs have long been associated with cancer development and progression, and since their earliest discovery, their clinical potential in identifying and characterizing the disease has been pursued. Long non-coding (lncRNAs), a diverse class of RNA transcripts >200 nucleotides in length with limited protein coding potential, has been only modestly studied relative to other categories of non-coding RNAs. However, recent data suggests they too may be important players in cancer.

Molecular Targeted Therapies in Hepatocellular Carcinoma: Past, Present and Future.

Hepatocellular carcinoma (HCC) is an aggressive tumor and the sixth most common form of cancer worldwide. Surgery is the gold-standard treatment for local disease and often complemented by radiofrequency ablation or transarterial chemoembolization. In advanced disease, therapy options are limited and relapse and metastasis are common.

A top-down view of the tumor microenvironment: structure, cells and signaling.

It is well established that the tumor microenvironment (TME) contributes to cancer progression. Stromal cells can be divided into mesenchymal, vascular, and immune. Signaling molecules secreted by the tumor corrupts these cells to create "activated" stroma.

Exosomal Non-Coding RNAs: Diagnostic, Prognostic and Therapeutic Applications in Cancer.

Non-coding RNAs, such as microRNAs and long non-coding RNAs, are important regulatory molecules which are corrupted in cancer, often in a tissue and stage specific manner. Accumulated data suggests that these promising biomarkers, may also form the basis of novel targeted therapeutic strategies. The role of exosomes in cancer development and metastasis pathways is also increasingly well described.

The clinical and biological significance of MIR-224 expression in colorectal cancer metastasis.

Objective: MicroRNA (miRNA) expression profile can be used as prognostic marker for human cancers. We aim to explore the significance of miRNAs in colorectal cancer (CRC) metastasis.

Design: We performed miRNA microarrays using primary CRC tissues from patients with and without metastasis, and validated selected candidates in 85 CRC samples by quantitative real-time PCR (qRT-PCR).

Stratifying risk of recurrence in stage II colorectal cancer using deregulated stromal and epithelial microRNAs.

MicroRNAs (miRNAs) enable colonic epithelial cells to acquire malignant characteristics and metastatic capabilities. Recently, cancer relevant miRNAs deregulated during disease progression have also been identified in tumor-associated stroma.By combining laser-microdissection (LMD) with high-throughput screening and high-sensitivity quantitation techniques, miRNA expression in colorectal cancer (CRC) specimens and paired normal colonic tissue was independently characterized in stromal and epithelial tissue compartments.

The significance of pretreatment anemia in the era of R-IPI and NCCN-IPI prognostic risk assessment tools: a dual-center study in diffuse large B-cell lymphoma patients.

Background: Anemia is frequently identified at the time of diagnosis in patients with diffuse large B-cell lymphoma (DLBCL); however, studies addressing the prognostic significance of this important clinical parameter are lacking.

Methods: In this dual-center study of patients with DLBCL (n = 556) treated with rituximab-containing regimens, we evaluated the prognostic relevance of anemia at diagnosis in a training set (n = 211) and validated our findings in a second independent patient cohort (n = 345). Using Kaplan-Meier curves as well as univariate and multivariate Cox regression models, we analyzed the impact of anemia on 5-year overall survival (OS) and 5-year disease-free survival (DFS) alongside established prognostic indicators including age, tumor stage, the revised International Prognostic Index (R-IPI), and the recently published NCCN-IPI.

Molecular profiling of the invasive tumor microenvironment in a 3-dimensional model of colorectal cancer cells and ex vivo fibroblasts.

Invading colorectal cancer (CRC) cells have acquired the capacity to break free from their sister cells, infiltrate the stroma, and remodel the extracellular matrix (ECM). Characterizing the biology of this phenotypically distinct group of cells could substantially improve our understanding of early events during the metastatic cascade. Tumor invasion is a dynamic process facilitated by bidirectional interactions between malignant epithelium and the cancer associated stroma.

miR-153 supports colorectal cancer progression via pleiotropic effects that enhance invasion and chemotherapeutic resistance.

Although microRNAs (miRNA) have been broadly studied in cancer, comparatively less is understood about their role in progression. Here we report that miR-153 has a dual role during progression of colorectal cancer by enhancing cellular invasiveness and platinum-based chemotherapy resistance. miRNA profiling revealed that miR-153 was highly expressed in a cellular model of advanced stage colorectal cancer.

MicroRNAs: critical regulators of epithelial to mesenchymal (EMT) and mesenchymal to epithelial transition (MET) in cancer progression.

MicroRNAs (miRNAs) are a class of small highly conserved RNAs that provide widespread expressional control through the translational repression of mRNA. MiRNAs have fundamental roles in the regulation of intracellular processes, and their importance during malignant transformation and metastasis is becoming increasingly well recognized. An important event in the metastatic cascade is epithelial to mesenchymal transition (EMT), a reversible phenotypic switch over, which endows malignant epithelial cells with the capacity to break free from one another and invade the surrounding stroma.