Molecular Imaging of Tumor-Infiltrating Lymphocytes in Living Animals Using a Novel mCD3 Fibronectin Scaffold.

The interaction between cancer cells and immune cells in the tumor microenvironment (TME) plays a crucial role in determining tumor growth, metastasis, and response to treatment. Tumor-infiltrating lymphocytes (TILs) in TME could be a predictive marker for treatment response in various therapeutic interventions, including chemotherapy and immunotherapy. Thus, imaging the tumor immune microenvironment is important for selecting the optimal treatment strategies in cancer therapy.

A mutant fitness compendium in Bifidobacteria reveals molecular determinants of colonization and host-microbe interactions.

Bifidobacteria commonly represent a dominant constituent of human gut microbiomes during infancy, influencing nutrition, immune development, and resistance to infection. Despite interest as a probiotic therapy, predicting the nutritional requirements and health-promoting effects of Bifidobacteria is challenging due to major knowledge gaps. To overcome these deficiencies, we used large-scale genetics to create a compendium of mutant fitness in ().

The dialectics of cancer: A theory of the initiation and development of cancer through errors in RNAi.

The recent discoveries of the RNA-mediated interference system in cells could explain all of the known features of human carcinogenesis. A key, novel idea, proposed here, is that the cell has the ability to recognise a mutated protein and/or mRNA. Secondly, the cell can generate its own short interfering RNA (siRNA) using an RNA polymerase to destroy mutated mRNA, even when only a single base pair in the gene has mutated.

DNA methylation patterns in adenomas from FAP, multiple adenoma and sporadic colorectal carcinoma patients.

Colorectal adenomas have traditionally been regarded as homogeneous. The aim of our study was to identify molecular features that may differentiate sporadic adenomas from familial adenomas such as Familial Adenomatous Polyposis (FAP) and Multiple Adenoma patients. DNA methylation was tested at Methylated IN Tumor (MINT) loci (1,2,12,31) and the CpG promoter region of genes MLH1, HPP1, MGMT, p14ARF and p16INK4a in FAP-associated adenomas (33) from 5 patients with a known APC mutation (Group 1, FAP), adenomas (29) from 4 Multiple Adenoma patients (Group 2 Multiple), adenomas (14) from 3 patients with sporadic colorectal cancers showing high microsatellite instability (Group 3, MSI-H) and adenomas (16) from 7 patients, with sporadic colorectal cancers showing microsatellite stable or low level instability (Group 4, MSS/MSI-L).

Promoter hypermethylation frequency and BRAF mutations distinguish hereditary non-polyposis colon cancer from sporadic MSI-H colon cancer.

Background: Colorectal cancers resulting from defective DNA mismatch repair can occur in both hereditary non-polyposis colon cancer (HNPCC) and in the sporadic setting. They are characterised by a high level of microsatellite instability (MSI-H) and superficially resemble each other in that they are frequently located in the proximal colon and share features such as circumscribed tumour margins and tumour-infiltrating lymphocytes. However, significant differences can be demonstrated at the molecular level including widespread promoter hypermethylation and BRAF -activating mutations which occur significantly less often in HNPCC.

BRAF mutation is associated with DNA methylation in serrated polyps and cancers of the colorectum.

Background And Aims: Mutations in BRAF have been linked with colorectal cancers (CRC) showing high level microsatellite instability (MSI-H). However, the distribution of BRAF mutations in MSI-H cancers remains to be clarified with respect to precursor lesions and the CpG island methylator phenotype (CIMP).

Methods: Forty three hyperplastic polyps (HP), nine mixed polyps (MP), five serrated adenomas (SA), 28 conventional adenomas (AD), 18 hereditary non-polyposis colorectal cancers (HNPCC), and 127 sporadic CRC (46 MSI-H and 81 non-MSI-H) were collected from patients undergoing colectomy for either CRC or hyperplastic polyposis.

Role of inherited defects of MYH in the development of sporadic colorectal cancer.

Biallelic germ-line variants of the 8-hydroxyguanine repair gene MYH have been associated with multiple colorectal adenomas that display somatic G:C-->T:A transversions in APC. However, the effect of single germ-line variants has not been widely studied. To examine the relationship between monoallelic MYH variants and susceptibility to sporadic colorectal cancer (CRC), 92 cases of sporadic CRC, 19 cases of familial CRC not meeting the Bethesda guidelines, 17 cases with multiple adenomas, and 53 normal blood donors were screened for 8 potentially pathogenic germ-line MYH variants.

Methylation patterns define two types of hyperplastic polyp associated with colorectal cancer.

Aim: Hyperplastic polyps (HP) of the colorectum have traditionally been regarded as non-neoplastic lesions. Recent data implicate HP in the pathogenesis of colorectal cancers (CRC) characterised by extensive DNA methylation and microsatellite instability. The aim of this study was to identify morphological and molecular features that may characterise subtypes of HP with potential for neoplastic progression.

Morphological and molecular heterogeneity within nonmicrosatellite instability-high colorectal cancer.

Colorectal cancer (CRC) has traditionally been classified into two groups: microsatellite stable/low-level instability (MSS/MSI-L) and high-level MSI (MSI-H) groups on the basis of multiple molecular and clinicopathologic criteria. Using methylated in tumor (MINT) markers 1, 2, 12, and 31, we stratified 77 primary CRCs into three groups: MINT++ (>2), MINT+ (1-2), and MINT- (0 markers methylated). The MSS/MSI-L/MINT++ group was indistinguishable from the MSI-H/MINT++ group with respect to methylation of p16(INK4a), p14(ARF), and RIZ1, and multiple morphological features.

Features of colorectal cancers with high-level microsatellite instability occurring in familial and sporadic settings: parallel pathways of tumorigenesis.

High-level microsatellite instability (MSI-H) is demonstrated in 10 to 15% of sporadic colorectal cancers and in most cancers presenting in the inherited condition hereditary nonpolyposis colorectal cancer (HNPCC). Distinction between these categories of MSI-H cancer is of clinical importance and the aim of this study was to assess clinical, pathological, and molecular features that might be discriminatory. One hundred and twelve MSI-H colorectal cancers from families fulfilling the Bethesda criteria were compared with 57 sporadic MSI-H colorectal cancers.

Angiogenic factor VEGF is decreased in human colorectal neoplasms showing DNA microsatellite instability.

Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are two important determinants of angiogenesis in human cancers. Expression of VEGF and bFGF was examined by immunohistochemistry in 120 colorectal cancers. Neoplasms were classified according to the presence or absence of microsatellite instability determined at six microsatellite loci and labelled as a high microsatellite instability (MSI-H), low microsatellite instability (MSI-L) or microsatellite stable (MSS).

Morphology of sporadic colorectal cancer with DNA replication errors.

Background: Up to 15% of colorectal cancers are characterised by DNA microsatellite instability (MIN), shown by the presence of DNA replication errors (RERs).

Aims: To identify pathological features that are discriminating for colorectal cancer (CRC) showing extensive MIN.

Subjects: A prospective series of 303 patients with CRC and no family history of either familial adenomatous polyposis or hereditary non-polyposis colorectal cancer.

Endotoxin levels in donors and recipients during orthotopic liver transplantation.

Background: The hypothesis being tested in this paper is that endotoxin levels in donors and in recipients during liver transplantation influences postoperative outcome.

Methods: Endotoxin levels in systemic venous and portal venous blood were measured using in 46 adult donors and 44 adult recipients (47 liver transplants) during the period 1992-95. Endotoxin was measured using a modification of the Limulus amoebocyte lysate (LAL) assay.

A novel thermostable dextranase from a Thermoanaerobacter species cultured from the geothermal waters of the Great Artesian Basin of Australia.

A Gram-negative sporulating thermophilic anaerobe, designated AB11Ad, was isolated from the heated waters of the Great Artesian Basin of Australia. It grew on a variety of carbohydrates including glucose, starch, and dextran and produced a thermostable and thermoactive extracellular endo-dextranase. The enzyme was produced more actively under pH controlled continuous culture conditions than under batch conditions.

Cytomegalovirus associated with acalculous cholecystitis in a patient with acquired immune deficiency syndrome.

Cytomegalovirus (CMV) is an opportunistic organism known to cause significant gastrointestinal pathology in patients with the acquired immune deficiency syndrome (AIDS). Hepatobiliary involvement has previously been documented. In this report, we discuss the rare entity of acalculous cholecystitis associated with CMV intranuclear inclusion bodies in an AIDS patient.

The effect of convulsions induced by flurothyl on ribonucleic acid synthesis in rat cerebral cortex during the recovery phase.

The effect of convulsions, induced by flurothyl, on RNA synthesis in purified unfractionated nuclei and the cytoplasm of rat cerebral cortex was studied by using a double-label technique involving injection of [3H]- and [14C]-orotate intracisternally. 2. Intact RNA was extracted in 80% yield by an enzymic method by using a proteinase in the presence of sodium dodecyl sulphate followed by deoxyribonuclease.