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PubMed2004

Chemical synthesis of normal and transformed PSA glycopeptides.

Chemical syntheses are reported for prostate specific antigen (PSA) N-linked glycopeptide fragments consisting of an uneicosapeptide (residues 27-47 of PSA) with di-, tri-, and tetrabranched N-acetyllactosamine-type glycans. The syntheses involve simultaneous, multiple glycosylations of the corresponding pentasaccharide acceptors prepared from a common trisaccharide precursor. Globally deprotected glycans are aminated and then aspartylated with a hexapeptide, which is then extended using native chemical ligation (NCL). The glycopeptides will be used for the generation of antibodies that may form the basis for a new prostate cancer diagnostic assay.

Amino Acid Sequence↗

PubMed2004

Time-of-flight optophoresis analysis of live whole cells in microfluidic channels.

Optophoresis is a non-invasive cell analysis technique that is based on the interaction of live whole cells with optical gradient fields, typically generated by a near-infrared laser. The magnitude of the interaction depends upon the intrinsic physical properties of the cells, such as their refractive index, composition, size, and morphology. Time-of-flight (TOF) optophoresis is an implementation of this technique in a microfluidic environment. It measures cell travel times through a fixed distance with and without irradiation from a laser beam. The magnitude of the optical force from the laser, and therefore the change in transit time introduced by the presence of the infrared laser provides a signature for the cell. By accumulating such measurements for a population of cells (typically 200-300 cells per population), different cell types, drug treatments, or biological states can be compared quantitatively without the need for external labels or markers. An integrated TOF system has been constructed and characterized. The system typically uses square capillaries with 50-100 microm internal diameter and uses a syringe-pump-based flow system that generates initial bulk flow velocities between 200 and 600 microm/sec. Using this TOF technique, we have been able to consistently detect significant differences between normal skin and melanoma cell lines, CCD-1037 and A375, respectively. We have also been able to measure consistent differences in a cell differentiation model (HL60 cell line with DMSO treatment). These early results indicate the potential biological sensitivity of the TOF measurement technique for cellular analysis and cancer diagnostic applications.

Cell Line, Tumor↗

PubMed2004

[PSA-screening for prostate cancer--yes or no?].

Prostate cancer is a mayor health care problem, especially in the industrialised countries of the Western world. At this time it is the second most common cancer reason for death (CH: 1500 men/year) which will even get more importance in the future by demographic developments. While there is no doubt that in individuals early detection of organ confined disease with localised treatment the prostate cancer can be eradicated and individual men be cured there are uncertainties whether mass screening a population will contribute to reducing prostate cancer related mortality. Its value has not been proved definitively by prospective randomised controlled studies. Most of Medical Societies recommend a "well informed" decision by family physicians, where the men between 50-70 years know about the benefits and harms including: risk of cancer, diagnostic procedures, therapeutic consequences and possible side effects. After agreement of early detection a biopsy has to be done directly above a PSA level of 4.0 ng/ml or a suspicious digital rectal examination. A PSA "grey zone" 4-10 ng/ml can not further be postulated. The ratio of free/total PSA gives no support to prolong biopsy in this moment, because an elevated benign prostate with a higher production of free PSA can mask the tumor in the peripheral zone. Results of the ERSPC and the PLCO trials are expected to give information about the benefits and harms of mass screening in 2006/8.

Aged↗

PubMedDate not supplied

Immunohistochemical detection of telomerase (hTERT) protein in human cancer tissues and a subset of cells in normal tissues.

We examined human telomerase reverse transcriptase (hTERT) protein distribution by immunohistochemistry in cultured cells and tissue sections. Cells with telomerase activity had nuclear positive signals whereas cells without telomerase activity did not. In most normal epithelial tissues, hTERT expression was prominent in the early proliferative descendent progenitors cells. In cancers with high telomerase activity, hTERT expression was detected in almost all neoplastic cells and correlated with telomerase activity levels, whereas cancers with low telomerase activity had fewer hTERT-positive cancer cells. In pediatric neuroblastomas with a favorable outcome, both the percentage of positive cells and the signal intensities of each hTERT-expressing cell decreased. These studies indicate that detection of telomerase at the cellular level is achievable and may have utility in cancer diagnostics.

Adult↗

PubMed2002

Expression profiling of primary non-small cell lung cancer for target identification.

Using a panel of cDNA microarrays comprising 47 650 transcript elements, we have carried out a dual-channel analysis of gene expression in 39 resected primary human non-small cell lung tumours versus normal lung tissue. Whilst approximately 11 000 elements were scored as differentially expressed at least twofold in at least one sample, 96 transcripts were scored as over-represented fourfold or more in at least seven out of 39 tumours and 30 sequences 16-fold in at least two out of 39 tumours, including 24 transcripts in common. Transcripts (178) were found under-represented fourfold in at least seven out of 39 tumours, 31 of which are under-represented 16-fold in at least two out of 39 lesions. The relative expression levels of representative genes from these lists were analysed by comparative multiplex RT-PCR and found to be broadly consistent with the microarray data. Two dramatically over-represented genes, previously designated as potential tumour suppressors in breast (maspin) and lung and breast (S100A2) cancers, were analysed more extensively and demonstrate the effectiveness of this approach in identifying potential lung cancer diagnostic or therapeutic targets. Whilst it has been reported that S100A2 is downregulated in NSCLC at an early stage, our microarray, cmRT-PCR, Western and immunohistochemistry data indicate that it is strongly expressed in the majority of tumours.

Adult↗

PubMed2005

[Prostate biopsy -- practical examination of the adequacy of Chen's virtual strategy].

INTRODUCTION: Prostate sextant biopsy is considered the gold standard of invasive prostate cancer diagnostics. However, numerous studies have shown that greater detection rates are achieved by increasing the number of biopsies. Chen et al. found ten "ideal" biopsy sites using a computer model. This study examines the clinical value of this variation of number and localisation of biopsies. MATERIAL AND METHOD: Ultrasound-guided ten-core prostate biopsies are performed in our department. Following the model of Chen, three prostate biopsies instead of on are taken from the middle plane. The two additional specimens are obtained in the paraurethral and ventral regions. RESULTS: Between July 2003 and February 2004, 191 patients scheduled for a 10-core prostate biopsy were included in the study. Assessable results were obtained in 176 cases. A carcinoma was detected in 61/176 (34.7 %) of the patients. The carcinoma was found only in the standard sextant localisations (27.8 %) in 17/61 patients and additionally in the paraurethral or ventral region in 35/61 (57.3 %). The carcinoma was located only paraurethrally in 1/62 (1.6 %) and only ventrally in 6/62 (9.7 %). Altogether, the prostate carcinoma was detected only by the additional biopsies in 6 patients (9.8 %). A clinically relevant disease was seen in 5/6 (83.3 %). A carcinoma was detected most frequently in the following biopsies: base right (17.1 %), central lat. right (17.5 %) and apex right (16.5 %) and most rarely paraurethral right (12 %) and ventral right (10.2 %). Statistically significant differences were found only between these groups. CONCLUSION: The modification and increase of biopsies from six to ten according to the model suggested by Chen et al. detected 9.8 % more carcinomas in our patients.

Aged↗

PubMed2001

Multiclass cancer diagnosis using tumor gene expression signatures.

The optimal treatment of patients with cancer depends on establishing accurate diagnoses by using a complex combination of clinical and histopathological data. In some instances, this task is difficult or impossible because of atypical clinical presentation or histopathology. To determine whether the diagnosis of multiple common adult malignancies could be achieved purely by molecular classification, we subjected 218 tumor samples, spanning 14 common tumor types, and 90 normal tissue samples to oligonucleotide microarray gene expression analysis. The expression levels of 16,063 genes and expressed sequence tags were used to evaluate the accuracy of a multiclass classifier based on a support vector machine algorithm. Overall classification accuracy was 78%, far exceeding the accuracy of random classification (9%). Poorly differentiated cancers resulted in low-confidence predictions and could not be accurately classified according to their tissue of origin, indicating that they are molecularly distinct entities with dramatically different gene expression patterns compared with their well differentiated counterparts. Taken together, these results demonstrate the feasibility of accurate, multiclass molecular cancer classification and suggest a strategy for future clinical implementation of molecular cancer diagnostics.

Biomarkers, Tumor↗

PubMed1988

Thermostable DNA polymerase chain amplification of t(14;18) chromosome breakpoints and detection of minimal residual disease.

Achieving the capacity to detect minimal numbers of neoplastic cells is a major cancer diagnostic challenge. Chromosomal translocations such as the t(14;18)(q32;q21) found in follicular and some nonfollicular lymphomas provide a tumor-specific molecular marker. The 14;18 breakpoints are focused at one of six immunoglobulin heavy chain joining (JH) regions on chromosome 14 and a small major breakpoint region (MBR) of the BCL2 gene on chromosome 18. We utilized universal oligonucleotide primers of a region 5' to the BCL2 MBR and at the 3' end of JH segments to initiate a DNA polymerase chain reaction that amplified these BCL2-JH junctures. Use of thermostable DNA polymerase enabled annealing and synthesis steps at temperatures approaching the melting point of the primers, providing a sensitive and specific assay capable of detecting 1 lymphoma cell in 10(6) normal cells. This technique identified the subclinical presence of leukemic cells in all seven patients examined, including two in clinical remission. It also assessed the effectiveness of protocols designed to purge malignant cells from marrow. Moreover, this approach enabled the rapid DNA sequencing of chromosomal breakpoints without their molecular cloning. This assay markedly refines the capacity to detect minimal residual disease and should improve the ability to determine the stage of disease, stratify treatment, and evaluate therapy.

Bacterial Proteins↗

PubMed2003

Classification of breast masses in ultrasonic B scans using Nakagami and K distributions.

Classification of breast masses in greyscale ultrasound images is undertaken using a multiparameter approach. Five parameters reflecting the non-Rayleigh nature of the backscattered echo were used. These parameters, based mostly on the Nakagami and K distributions, were extracted from the envelope of the echoes at the site, boundary, spiculated region and shadow of the mass. They were combined to create a linear discriminant. The performance of this discriminant for the classification of breast masses was studied using a data set consisting of 70 benign and 29 malignant cases. The Az value for the discriminant was 0.96 +/- 0.02, showing great promise in the classification of masses into benign and malignant ones. The discriminant was combined with the level of suspicion values of the radiologist leading to an Az value of 0.97 +/- 0.014. The parameters used here can be calculated with minimal clinical intervention, so the method proposed here may therefore be easily implemented in an automated fashion. These results also support the recent reports suggesting that ultrasound may help as an adjunct to mammography in breast cancer diagnostics to enhance the classification of breast masses.

Adult↗

PubMed2025

Neighborhood enrichment for the identification of antigen-specific T-cell receptors.

Understanding T-cell receptor (TCR) specificity is not only essential for fundamental research, but could open up novel avenues for diagnostics, cancer immunotherapy, and the targeted treatment of autoimmune diseases. The immune system responds to challenges through groups of T-cells with similar TCR sequences. In recent years, searching for TCRs with an enrichment of similar sequences - neighbors - in a TCR repertoire has become a standard procedure for antigen-specific TCR identification. This study provides a systematic comparison of computational algorithms-ALICE, TCRNET, GLIPH2, and tcrdist3-that leverage neighborhood enrichment for antigen-specific TCR identification. Using published murine datasets from Lymphocytic choriomeningitis virus (LCMV) infection and novel datasets from Sputnik V vaccination and Mycobacterium tuberculosis (Mtb) infection, we evaluated the performance of these algorithms. To facilitate reproducible analysis, we developed TCRgrapher, an R library that integrates these pipelines into a user-friendly framework. TCRgrapher enables efficient identification of antigen-specific TCRs from single repertoire snapshots and supports flexible parameter customization. Our comparative analysis revealed that ALICE and TCRNET consistently outperformed GLIPH2 and tcrdist3 across most datasets, achieving higher area under precision-recall curve. While murine datasets provide valuable insights into algorithm performance, caution is advised when extrapolating these results to other species or different experimental conditions. TCRgrapher is freely available on GitHub (https://github.com/KseniaMIPT/tcrgrapher), offering researchers a robust tool for investigating TCR specificity and advancing immunological studies.

Animals↗

PubMed2025

HallmarkGraph: a cancer hallmark informed graph neural network for classifying hierarchical tumor subtypes.

MOTIVATION: Accurate tumor subtype diagnosis is crucial for precision oncology, yet current methodologies face significant challenges. These include balancing model accuracy with interpretability and the high costs of generating multi-omics data in clinical settings. Moreover, there is a lack of validated models capable of classifying hierarchical tumor subtypes across a comprehensive pan-cancer cohort. RESULTS: We present a graph neural network, HallmarkGraph, the first biologically informed model developed to classify hierarchical tumor subtypes in human cancer. Inspired by cancer hallmarks, the model's architecture integrates transcriptome profiles and gene regulatory interactions to perform multi-label classification. We evaluate the model on a comprehensive pan-cancer cohort comprising 11 476 samples from 26 primary cancers with 405 subtypes up to eight levels. The model demonstrates exceptional performance, achieving 5-fold cross-validation accuracy between 85% and 99% for tumor subtypes labeled with increasing details of genomic information. It also shows good generalizability on a validation dataset of 887 samples, assessed using three metrics that consider tumor subtypes at individual, combined, and sample levels. Benchmarking and ablation experiments show that hallmark-based embeddings slightly influence model performance, while the integrated multilayer perceptron plays a significant role in determining classifier accuracy. Additionally, we use the SHAP method to link cancer hallmarks with genes, identifying key features that influence model decisions. Our findings present a biologically informed machine learning framework capable of tracking tumor transcriptomic trajectories and distinguishing inter- and intra-tumor heterogeneity in pan-cancer. This approach holds promise for enhancing cancer diagnostics. AVAILABILITY AND IMPLEMENTATION: HallmarkGraph is accessible at https://github.com/laixn/HallmarkGraph.

Humans↗

PubMed2026

New Evidence in Heart Failure: 2026 Update.

Heart failure (HF) remains a major cause of morbidity, mortality, impaired quality of life and healthcare expenditure worldwide. The global burden of HF continues to increase due to population aging, improved survival, and the growing prevalence of cardiovascular, renal, and metabolic comorbidities. Simultaneously, the pace of scientific progress in HF has accelerated considerably. Recent advances have refined our understanding of HF epidemiology, prognosis, and disease trajectories, including emerging concepts of HF improvement, remission, and recovery. The Second Universal Definition of HF has also updated the classification framework, moving beyond the traditional ejection fraction-based categories. HF is now broadly classified into two major phenotypes: heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Novel mechanistic insights highlight the role of inflammation, immune activation, metabolic dysfunction, mitochondrial biology, and multisystem interactions in HF progression. There has also been significant progress in the characterization and management of major comorbidities, including chronic kidney disease (CKD), diabetes, obesity, atrial fibrillation (AF), pulmonary hypertension, frailty, malnutrition, and cancer. Diagnostic innovations include novel biomarkers, multi-omics technologies, artificial intelligence-based approaches, advanced imaging techniques, congestion assessment tools, and emerging digital health solutions. Important advances have occurred in specific HF aetiologies, including cardiomyopathies, cardiac amyloidosis (CA), myocarditis, arrhythmia-induced cardiomyopathy (AiCM), and Chagas cardiomyopathy. Therapeutic developments continue to reshape HF management across the spectrum of left ventricular ejection fraction. Recent evidence has focused on optimization of guideline-directed medical therapy in HFrEF, expansion of evidence-based therapies in HFpEF, and growing roles for sodium-glucose cotransporter-2 inhibitors, finerenone, incretin-based therapies, and transcatheter valve interventions. Collectively, these advances support the transition from a predominantly phenotype-based approach towards a more personalized and biologically informed model of HF care, with the potential to further improve outcomes across the entire HF spectrum.

Journal Article↗

PubMed1997

Structure determination of N-linked oligosaccharides engineered at the CH1 domain of humanized LL2.

Two humanized antibody mutants, hLL2HCN1 and hLL2HCN5, engineered with CH1 domain-appended carbohydrates (CHOs) were generated to facilitate site-specific conjugation of radionuclides and anti-cancer drugs to antibodies. Such site-specific conjugation may minimize the incidence of immunoreactivity perturbation as is often observed with random conjugation. Since the compositions and structures of CHOs are important in determining the chemistry, efficiency, and extent of conjugation, the sequences of the CH1-appended CHOs were determined by exoglycosidase digestions and fluorophore-assisted CHO electrophoresis (FACE). The CHO species attached at HCN1 and HCN5 sites in hLL2HCN1 and hLL2HCN5, respectively, were distinct from each other, heterogeneous, and extensively processed. All of these CHOs were core-fucosylated complex-type oligosaccharides and contained Gal (galactose) and GlcNAc (N-acetylglucosamine) residues in the outer branches. Some of the outer branches were composed of Gal alpha1-3Galbeta1-4GlcNAc structure, also known as alpha-galactosyl epitope. Most of the CHOs were sialylated. While all HCN1-CHOs were biantennary, the majority of HCN5-CHOs (>60%) were triantennary. The CH1-appended CHOs have favorable structural characteristics suitable for site-specific conjugation. For efficient conjugation of large drug complexes, hLL2HCN5 is preferable to hLL2HCN1 because the attached CHO is larger in size and more remotely positioned from the V region. The effects of the alpha-galactosyl epitope found in these CHOs on the immunological properties of the immunoconjugates as efficient cancer diagnostics and therapeutics are being studied.

Antibodies, Monoclonal↗

PubMed2003

Prescriptions for health providers: from cancer patients.

Women enter an increasingly complex medical system when they receive the diagnosis of breast cancer. Subsequently, they are confronted with numerous complicated, confusing, and less than certain decision-making episodes. Research was undertaken to follow and observe in vivo medical encounters between women and their oncologic physicians throughout the breast cancer diagnostic and treatment process. Empirical data was collected using qualitative techniques to deepen understanding of the decision-making process in the oncology setting. Physicians and patients alike make assumptions about each other that can hinder the development of a trusting and caring attitude that enables a more efficient delivery of healthcare. Patients offer recommendations for care to their physicians. In addition, ethical concerns regarding how medical options are presented to patients emerged in this study.

Adult↗

PubMed2001

Chlamydia trachomatis disguised as an asymptomatic scrotal mass in adolescents.

We present two cases of adolescents who presented with painless scrotal masses suggestive of testicular cancer. Diagnostic workup of both these patients revealed Chlamydia trachomatis and both patients were successfully treated with doxycycline. Both patients initially denied sexual activity. We suggest that a high index of suspicion is warranted in adolescent patients that present with asymptomatic scrotal masses and precise tests for C. trachomatis be done to rule out an infectious cause.

Adolescent↗

PubMed1977

Xeromammography--a reason for using saline-filled breast prostheses.

In 5 patients, silicone gel implants obscurred the image, while in 5 patients with saline-filled implants a good 3-dimensional examination of the breast was possible with xeromammography. If saline-filled implants routinely allow better cancer diagnostic surveillance than do silicone gel implants, this should be considered by the surgeon at the time he does an augmentation mammaplasty.

Breast↗

PubMed2002

Active microelectronic array system for DNA hybridization, genotyping and pharmacogenomic applications.

Microelectronic arrays have been developed for DNA hybridization analysis of point mutations, single nucleotide polymorphisms, short tandem repeats and gene expression. In addition to a variety of molecular biology and genomic research applications, such devices will also be used for infectious disease detection, genetic and cancer diagnostics, and pharmacogenomic applications. These microelectronic array devices are able to produce defined electric fields on their surfaces that allow charged molecules and other entities to be transported to or from any test site or micro-location on the planar surface of the device. These molecules and entities include DNA, RNA, proteins, enzymes, antibodies and cells. Electronic-based molecule addressing and hybridization can then be carried out, where the electric field is now used to greatly accelerate the hybridization reactions that occur on the selected test sites. When reversed, the electric field can be used to provide an additional parameter for improved hybridization. Special low-conductance buffers have been developed that provide for the rapid transport of the DNA molecules and facilitate the electronic hybridization reactions under conditions that do not support hybridization. Important to the device function is the permeation layer that overcoats the underlying microelectrodes. Generally composed of a porous hydrogel material impregnated with attachment chemistry, this permeation layer prevents the destruction of analytes at the active microelectrode surface, ameliorates the adverse effects of electrolysis products on the sensitive hybridization and affinity reactions, and serves as a support structure for attaching DNA probes and other molecules to the array. The microelectronic chip or array device is incorporated into a cartridge package (NanoChip trade mark cartridge) that provides the electronic, optical, and fluidic interfacing. A complete instrument system (NanoChip trade mark Molecular Biology Workstation) provides a chip loader, fluorescent reader, computer control interface and data display screen. The probe loader component allows DNA probes or target molecules (polymerase chain reactions amplicons, genomic DNA, RNA, etc.) to be selectively addressed to the array test sites, providing the end-user with 'make your own chip' capabilities. The electronic hybridization can then be carried out and the chip analyzed using a fluorescent detector system. In addition to carrying out rapid, accurate and highly reliable genotyping (point mutations, single nucleotide polymorphisms, short tandem repeats), other future applications include gene expression analysis, or on-chip amplification, immunoassays and cell separation and selection. Smaller and more compact systems are also being designed for portable sample to answer and point of care diagnostics.

DNA Probes↗

PubMed1991

Expression of blood group-related carbohydrate antigens in normal human pancreatic tissue.

The expression of type 1, 2 and 3 chain carbohydrate structures in 15 normal pancreata was investigated by immunohistochemical methods using well-defined monoclonal antibodies. Surgical biopsies of pancreata were obtained from kidney donors while the organs were still perfused. Type 1 chain structures were abundantly expressed including monosialylated(ms)- and disialylated(ds)-Le(a) antigens, which have previously been associated with cancer. Type 2 chain structures were represented by H and Le(y) antigens and to a lesser extent by the precursor structure N-acetyllactosamine, whereas Le(x), dimeric Le(x), and ms-Le(x) were only sporadically observed, in contrast to fetal pancreatic tissue, in which Le(x) has been found to be abundantly expressed. H chain 3 antigen was found in nearly all specimens, whereas precursor structures Tn, sial-Tn and T antigens were absent. Desialylation unmasked the T antigen in all specimens. Absence/masking of Tn, T and related antigens is of special interest, since these antigens are associated with tumor development in other tissues, and may be of importance in pancreatic cancer diagnostics in the future.

Adolescent↗