Profiling the heterogeneity of colorectal cancer consensus molecular subtypes using spatial transcriptomics.

The consensus molecular subtypes (CMS) of colorectal cancer (CRC) is the most widely-used gene expression-based classification and has contributed to a better understanding of disease heterogeneity and prognosis. Nevertheless, CMS intratumoral heterogeneity restricts its clinical application, stressing the necessity of further characterizing the composition and architecture of CRC. Here, we used Spatial Transcriptomics (ST) in combination with single-cell RNA sequencing (scRNA-seq) to decipher the spatially resolved cellular and molecular composition of CRC.

Characterization of Breast Cancer Preclinical Models Reveals a Specific Pattern of Macrophage Polarization.

Drug discovery efforts have focused on the tumor microenvironment in recent years. However, few studies have characterized the stroma component in patient-derived xenografts (PDXs) and genetically engineered mouse models (GEMs). In this study, we characterized the stroma in various models of breast cancer tumors in mice.

Predictive gene signature of response to the anti-TweakR mAb PDL192 in patient-derived breast cancer xenografts.

Purpose: (1) To determine TweakR expression in human breast cancers (BC), (2) evaluate the antitumor effect of the anti-TweakR antibody PDL192, used alone or after chemotherapy-induced complete remission (CR), on patient-derived BC xenografts (PDX) and (3) define predictive markers of response.

Experimental Design: TweakR expression was analyzed by IHC on patients and PDXs BC samples. In vivo antitumor effect of PDL192 was evaluated on eight TweakR-positive BC PDXs alone or after complete remission induced by a combination of doxorubicin and cyclophosphamide.

TTK/hMPS1 is an attractive therapeutic target for triple-negative breast cancer.

Triple-negative breast cancer (TNBC) represents a subgroup of breast cancers (BC) associated with the most aggressive clinical behavior. No targeted therapy is currently available for the treatment of patients with TNBC. In order to discover potential therapeutic targets, we searched for protein kinases that are overexpressed in human TNBC biopsies and whose silencing in TNBC cell lines causes cell death.

Polo-like kinase 1: a potential therapeutic option in combination with conventional chemotherapy for the management of patients with triple-negative breast cancer.

Breast cancers are composed of molecularly distinct subtypes with different clinical outcomes and responses to therapy. To discover potential therapeutic targets for the poor prognosis-associated triple-negative breast cancer (TNBC), gene expression profiling was carried out on a cohort of 130 breast cancer samples. Polo-like kinase 1 (PLK1) was found to be significantly overexpressed in TNBC compared with the other breast cancer subtypes.

Group acupuncture for knee pain: evaluation of a cost-saving initiative in the health service.

Background: Acupuncture has been provided in nurse-led group clinics in St Albans since 2008. It is funded by a commissioning group within the National Health Service, on a trial basis, for patients with knee osteoarthritis who would otherwise be referred to an orthopaedic surgeon.

Aim: To evaluate the patients seen in the service's first year of operation and their outcome up to the end of 2010.

The fibroblast growth factor receptor 1 (FGFR1), a marker of response to chemoradiotherapy in breast cancer?

The goal of the present study was to evaluate the role of the tyrosine kinase receptor fibroblast growth factor-1 (FGFR1) and its ligand, the fibroblast growth factor 2 (FGF2) in determining the response to chemoradiotherapy of breast cancers. S14 was a phase II neoadjuvant study carried out at the Institut Curie that recruited 59 patients between November 2001 and September 2003. This prospective study aimed to assess the pathological response after preoperative radiochemotherapy (5FU-Navelbine-radiotherapy) for large breast cancers.

Oxidative stress promotes myofibroblast differentiation and tumour spreading.

JunD regulates genes involved in antioxidant defence. We took advantage of the chronic oxidative stress resulting from junD deletion to examine the role of reactive oxygen species (ROS) in tumour development. In a model of mammary carcinogenesis, junD inactivation increased tumour incidence and revealed an associated reactive stroma.

Electric powered wheelchairs for those with muscular dystrophy: problems of posture, pain and deformity.

Purpose: To identify areas of difficulty encountered by a regional wheelchair service in providing Electric Powered Indoor/outdoor wheelchairs (EPIOCs) to those with muscular dystrophy (MD) in the early years of their provision--particularly posture, pain and deformity.

Method: Wheelchair service records of all users between April 1997 and March 2000 were reviewed retrospectively and issues relating to weakness, pain/discomfort, deformities, other medical issues, weight change, function, posture and driving were documented on a purpose-designed proforma. Adjustments and modifications were documented over the 2-year period following chair delivery.

Setting up an acupuncture knee clinic under Practice Based Commissioning.

This paper outlines the setting up of a new service in primary care offering acupuncture to patients with severe osteoarthritis of the knee. The high volume clinic is funded under the Practice Based Commissioning initiative and is the first of its type in the UK. It appears to offer a model for similar services elsewhere.

Hearing and balance. Part 1--the outer and middle ear.

This article is the first in a four-part series on hearing and balance, continuing our exploration of the senses. It discusses the outer and middle chambers of the ear, whose primary function is to transmit sound to the auditory receptors in the inner ear (Allan, 2005).

Sense of sight: part two. Seeing in colour, detail and depth.

This article is the second in a three-part series on the sense of sight. It forms part of a larger series on the special senses. The first article on sight examined the structures of the eye, the visual pathway and various disorders of the eye.

Exploring various methods for closing traumatic wounds.

This article describes the advantages and disadvantages of various methods used to close traumatic wounds.