Cationic Amphiphilic Drugs Boost the Lysosomal Escape of Small Nucleic Acid Therapeutics in a Nanocarrier-Dependent Manner.

Small nucleic acid (NA) therapeutics, such as small interfering RNA (siRNA), are generally formulated in nanoparticles (NPs) to overcome the multiple extra- and intracellular barriers upon administration. Interaction with target cells typically triggers endocytosis and sequesters the NPs in endosomes, thus hampering the pharmacological activity of the encapsulated siRNAs that occurs in the cytosol. Unfortunately, for most state-of-the-art NPs, endosomal escape is largely inefficient.

Obstetrical and epidemiological factors influence the severity of anal incontinence after obstetric anal sphincter injury.

Background: Obstetric anal sphincter injury (OASI) is one of the most severe obstetrical complications. Although risk factors for OASI have been identified, little is known about various parameters that can influence symptoms' severity. The aim of this study is to explore whether obstetrical and epidemiological factors can have an effect on the severity of symptoms after OASI.

Repurposing cationic amphiphilic drugs as adjuvants to induce lysosomal siRNA escape in nanogel transfected cells.

Cytosolic delivery remains a major bottleneck for siRNA therapeutics. To facilitate delivery, siRNAs are often enclosed in nanoparticles (NPs). However, upon endocytosis such NPs are mainly trafficked towards lysosomes.

Choose your cell model wisely: The in vitro nanoneurotoxicity of differentially coated iron oxide nanoparticles for neural cell labeling.

Unlabelled: Currently, there is a large interest in the labeling of neural stem cells (NSCs) with iron oxide nanoparticles (IONPs) to allow MRI-guided detection after transplantation in regenerative medicine. For such biomedical applications, excluding nanotoxicity is key. Nanosafety is primarily evaluated in vitro where an immortalized or cancer cell line of murine origin is often applied, which is not necessarily an ideal cell model.

Cytosolic Delivery of Nanolabels Prevents Their Asymmetric Inheritance and Enables Extended Quantitative in Vivo Cell Imaging.

Long-term in vivo imaging of cells is crucial for the understanding of cellular fate in biological processes in cancer research, immunology, or in cell-based therapies such as beta cell transplantation in type I diabetes or stem cell therapy. Traditionally, cell labeling with the desired contrast agent occurs ex vivo via spontaneous endocytosis, which is a variable and slow process that requires optimization for each particular label-cell type combination. Following endocytic uptake, the contrast agents mostly remain entrapped in the endolysosomal compartment, which leads to signal instability, cytotoxicity, and asymmetric inheritance of the labels upon cell division.

The impact of species and cell type on the nanosafety profile of iron oxide nanoparticles in neural cells.

Background: While nanotechnology is advancing rapidly, nanosafety tends to lag behind since general mechanistic insights into cell-nanoparticle (NP) interactions remain rare. To tackle this issue, standardization of nanosafety assessment is imperative. In this regard, we believe that the cell type selection should not be overlooked since the applicability of cell lines could be questioned given their altered phenotype.

Assessing nanoparticle toxicity in cell-based assays: influence of cell culture parameters and optimized models for bridging the in vitro-in vivo gap.

The number of newly engineered nanomaterials is vastly increasing along with their applications. Despite the fact that there is a lot of interest and effort is being put into the development of nano-based biomedical applications, the level of translational clinical output remains limited due to uncertainty in the toxicological profiles of the nanoparticles (NPs). As NPs used in biomedicines are likely to directly interact with cells and biomolecules, it is imperative to rule out any adverse effect before they can be safely applied.

Suspected gouty tophus in a woman's breast.

A postmenopausal woman treated with diuretics for hypertension and who underwent surgery for a previous fibroadenoma of the left breast presented, in December 2003, with a sudden bloody discharge of the left nipple with local swelling, redness, and pain. Radiologic investigations revealed a well-delimited tumor under the areola. Needle aspiration disclosed many histiocytes but no bacteria.

Molecular and clinical characteristics in 32 families affected with familial adenomatous polyposis.

Germ-line mutations in the 5' half of the Adenomatous Polyposis Coli (APC) gene are found in about 80% of the patients affected with familial adenomatous polyposis (FAP). The vast majority of these are nonsense or frameshift mutations which result in the loss of the carboxyl terminus of the APC protein. Using an in vivo assay in yeast, we have identified pathogenic germ-line mutations in 26 of 32 (81%) unrelated Swiss families affected with FAP.

Reproducibility of histopathologic diagnosis and classification of non-melanocytic skin cancer: a panel exercise in the framework of the multicenter southern European study HELIOS.

Aims And Background: The reproducibility of histologic diagnoses, and in particular of the distinction between basal and squamous cell forms, has been evaluated in the framework of a multicenter case-control study (in Italy, France, Spain and Switzerland) aimed to assess the causes of non-melanocytic skin cancers.

Methods: A panel composed of 10 pathologists from the collaborating centers was appointed. A total of 1,774 slides of routine diagnoses were blindly reviewed by a second panelist; discordant diagnoses underwent a third examination.

Surgical management of epithelial ovarian cancer at community hospitals: A population-based study.

Background And Objectives: Accurate surgical staging and maximal tumor reduction are the basic management principles of epithelial ovarian cancer (EOC). The purpose of our study is to report on staging practices and the primary surgery of EOC in a region that has no tertiary oncological referral center and no surgical gynecological oncologist.

Methods: Between 1 January 1989 and 30 December 1995, the Valais Cancer Registry had registered 157 patients with ovarian cancer stage I-IV.

How CA 125 is used in routine clinical practice.

The only role where the CA 125 test has proven utility is: (i) for monitoring ovarian cancer (OC); and (ii) for a preoperative test in patients with an ovarian mass. The aim of our study was to assess the clinical indications for CA 125 determinations in order to estimate the appropriateness of CA 125 use. During the period of 1 August 1993 through 31 December 1995 all CA 125 assays performed at the laboratory of the Institut Central des Hôpitaux Valaisans (ICHV) and the data of the patients receiving these tests were audited in order to identify the clinical indication for the test.

Risk of basal and squamous cell carcinomas of the skin in Sion, Switzerland: a case-control study.

Aims And Background: Non-melanocytic skin cancers are the most common cancers in white populations. Studies on populations of Anglo-Saxon and Mediterranean origins highlighted different patterns of risk of basal-cell carcinoma and squamous-cell carcinoma in relation to sunlight exposure, skin characteristics and phenotype susceptibility. In Sion, and in Switzerland as a whole, the high incidence suggests the possible presence of additional risk factors or of a different pattern of exposure to solar radiation as well as different composition of pigmentary traits and skin sensitivity to sun.

[Malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation and glandular component].

An exceptional case of malignant peripheral nerve sheath tumor with striated muscle differentiation and glandular component is reported, in a 52-year old man. This tumor measured 8 cm in diameter, and was localized in the chest wall, infiltrating the skeletal muscle. The mesenchymal portion of the tumor was composed mostly of spindle cells arranged in interlacing fascicles.

[Molecular pathology of colorectal cancer].

The identification of several types of familial colorectal cancer has led to the discovery of some of the genes involved in these diseases. It was subsequently shown that somatic mutations of these genes (APC, mismatch repair genes, TP53) also occur in sporadic colorectal cancer. Gradually, this molecular information is being incorporated into the standard histopathological analysis of colorectal cancer and can be used for the characterization of primary tumors.

[Pelvic hemangiopericytoma in pregnancy. Report of a case].

We report a case of pelvic retroperitoneal hemangiopericytoma (HPC) discovered early during pregnancy. Preoperative diagnosis was obtained by a transvaginal biopsy. Treatment consisted of therapeutic abortion, excision surgery and radiotherapy.

Excess of hMLH1 germline mutations in Swiss families with hereditary non-polyposis colorectal cancer.

Lynch syndrome, or hereditary non-polyposis colorectal cancer (HNPCC), is a consequence of a dominantly inherited susceptibility to accumulate somatic mutations. The disorder is manifested as a familial aggregation of colorectal cancers diagnosed at an early age and, to a lesser degree, of cancers of the endometrium, ovary, urinary tract, and organs of the gastrointestinal tract other than the colon. In more than half of the HNPCC families investigated, the cancer predisposition has been linked to germline mutations in one of the 2 genes hMLHI or hMSH2, involved in post-replicative DNA-mismatch repair.

Metastizing low-grade clear cell leiomyosarcoma of the uterus.

An unusual case of uterine clear cell tumor is reported in a 56-year-old woman. The neoplasm was identified as a peculiar low-grade leiomyosarcoma, composed mainly of watery, clear large cells with round, fairly regular nuclei. No appreciable pleomorphism or high mitotic activity was noted.

[Ovarian cancer: the symptoms and pathology. The cases of the Cantonal Cancer Registry (1989-1995)].

Background: Ovarian cancer is most frequently discovered at an advanced stage. The absence of symptoms in the early stages is thought to be the main reason for this late discovery. We tried to determine whether there are any specific signs or symptoms for early or late stages.

[From dysplastic nevus to malignant melanoma--a study of 4 anatomoclinical cases of dysplastic nevus syndrome].

Malignant melanoma (MM) is a skin neoplasm with an increasing incidence. Late discovery is often associated with lethal outcome. Among the possible precursor lesions of MM, the Dysplastic Naevus (DN) is a matter of controversy.

Systemic mastocytosis following a malignant ovarian germ cell tumour.

Cases of mediastinal germ cell tumours associated with haematological disorders (two cases of systemic mastocytosis included) have been reported previously. This combination is more frequent than would be expected by chance alone. We report the case of a 30-year-old woman, who presented with a systemic mastocytosis following a malignant ovarian germ cell tumour which was treated by chemo- and radiotherapy.