Circulating tumor cells and their clinical significance

Metastases to other organs and the formation of secondary tumors are responsible for 90% of cancer-related deaths. However, even in the early stages of cancer, about 30–40% of patients with localized disease may have latent metastasis, which are likely derived from circulating tumor cells (CTCs) involved in disease progression. Therefore, detection and analysis of CTCs can play an important role in the diagnosis and decision-making of adjuvant treat­ment that aims to prevent metastasis. At present, patients’ selection of treatment is based on the statistical risk of recurrence of metastatic disease, without considering whether the tumor cells have spread from the primary tumor. This may lead to unnecessary treatment of non-metastatic disease patients. Therefore, early detection of CTCs in the blood is critically important, and should allow for a more accurate assessment of disease severity. Here, we provide an overview of CTC phenotypes, including plasticity of CTCs, and their clinical significance

Circulating tumor cells and their clinical significance

Metastases to other organs and the formation of secondary tumors are responsible for 90% of cancer-related deaths. However, even in the early stages of cancer, about 30–40% of patients with localized disease may have latent metastasis, which are likely derived from circulating tumor cells (CTCs) involved in disease progression. Therefore, detection and analysis of CTCs can play an important role in the diagnosis and decision-making of adjuvant treat­ment that aims to prevent metastasis. At present, patients’ selection of treatment is based on the statistical risk of recurrence of metastatic disease, without considering whether the tumor cells have spread from the primary tumor. This may lead to unnecessary treatment of non-metastatic disease patients. Therefore, early detection of CTCs in the blood is critically important, and should allow for a more accurate assessment of disease severity. Here, we provide an overview of CTC phenotypes, including plasticity of CTCs, and their clinical significance

Clinical and neuropathological picture of familial encephalopathy with bifunctional protein deficiency

Peroxisomal diseases are a heterogeneous group of genetic metabolic disorders which are caused by incorrect biogenesis of peroxisomes or a defect in activity of particular enzymes located in those organelles. D-bifunctional protein (D-BP) deficiency belongs to the second group of peroxisomal diseases characterised by dysfunction of a single peroxisomal enzyme. Bifunctional protein is a catalyst in the second and third stage of the \beta-oxidation of fatty acids. Gene locus of bifunctional protein deficiency comprises chromosomes 5q2 and 3p23-p22. The authors present two siblings with progressing family encephalopathy. In the younger brother the diagnosis of a bifunctional protein deficiency was made. The girl died before a diagnosis was made; however, due to the presence of a very similar clinical condition a suspicion arises that the girl had a peroxisomal disease. In the siblings were ascertained characteristic dysmorphic features, delayed psychomotor development, polymorphic epileptic seizures and generalized muscular hypotonia with areflexia. The neuropathological findings were consistent in general with MRI findings showing features of hypomyelination. Also neuron heterotopias that were found in autopsy are a form of pathology typical for D-BP

Exploring the anti-apoptotic role of HAX-1 versus BCL-XL in cytokine-dependent bone marrow-derived cells from mice

AbstractHS-1-associated protein X-1 (HAX-1) is a multi-functional protein that has been implicated in the regulation of apoptosis, cell motility and calcium homeostasis. In the present study, we set out to assess the postulated functional resemblance of HAX-1 to the BCL-2 family of anti-apoptotic proteins using non-transformed, cytokine-dependent murine bone marrow cells as a model system. BCL-XL, but not HAX-1 protected against cytokine withdrawal-induced apoptosis while HAX-1 and BCL-XL significantly reduced thapsigargin-triggered (calcium-dependent) apoptosis. The data argue in favor of cell type- and stimulus-specific roles of HAX-1 in regulation of cell survival

The content of serotonin cells in duodenal biopsies of autistic patients

AbstractIntroductionAutistic spectrum disorders (ASD) don’t have the same etiology. Platelet hyperserotonemia remain the most common neurochemical abnormality in these patients. The main producer and storage of peripheral serotonin are enteric enterochromaffin cells – serotonin cells. Platelet hyperserotonemia may result from disorders in the synthesis and/or release of enteric serotonin. An increased number of people with ASD have gastrointestinal disorders. Some of them have a serotonergic background.AimThe aim was to assess the serotonin cells in the duodenal mucosa of patients with ASD.Material and methodsStudy group: 30 children with ASD, including 73% with duodenitis chronica. Control group (patients without ASD): 45 patients, 56% with duodenitis chronica. Immunohistochemical assessment of the number of serotonin cells was performed.’ResultsChildren with ASD and duodenitis have fewer serotonin cells than autistic children with a normal picture of the duodenum. Children with ASD and chronic duodenitis have fewer serotonin cells than patients from the control group. Patients from the control group, suffering from chronic duodenitis have an increased number of serotonin cells in relation to children without inflammatory lesions in the duodenum.ConclusionsThe serotonergic profiles of the GI tract of autistic patients and their peers without autistic symptoms are different. In the course of chronic duodenitis in patients with ASD the number of serotonin cells falls while in persons without autistic features it increases significantly. Chronic duodenitis contributes to an increase in the number of serotonin cells in persons without autistic features while decreasing it in patients with ASD

Migracja i inwazyjność komórek nowotworowych; rola plastyczności komórek i udział macierzy zewnątrzkomórkowej w tworzeniu przerzutów

Migratory and invasive potential of the cell is determined by the type of a tissue from which the cell derives. However, in case of neoplastic cells they display some plasticity of a phenotype which enables changes in the mode of migration. These transitions may influence the metastatic potential of the tumour. Processes described vitally depend on the tumour microenvironment and may be regulated by the dynamic of the extracellular matrix alterations.Zdolność komórek do migracji jest determinowana przez rodzaj tkanki, z jakiej się wywodzą. W przypadku komórek nowotworowych możliwa jest jednak pewna plastyczność fenotypu, umożliwiająca zmianę typu migracji. Zmiany te mogą mieć wpływ na poziom inwazyjności nowotworu. Opisywane procesy pozostają w ścisłej zależności od mikrośrodowiska, w jakim znajdują się komórki i mogą być regulowane przez zmiany zachodzące w macierzy zewnątrzkomórkowej, która w dynamiczny sposób wpływa na potencjał migracyjny i inwazyjny

High-throughput genotyping of a common deletion polymorphism disrupting the TRY6 gene and its association with breast cancer risk

<p>Abstract</p> <p>Background</p> <p>Copy number polymorphisms caused by genomic rearrangements like deletions, make a significant contribution to the genomic differences between two individuals and may add to disease predisposition. Therefore, genotyping of such deletion polymorphisms in case-control studies could give important insights into risk associations.</p> <p>Results</p> <p>We mapped the breakpoints and developed a fluorescent fragment analysis for a deletion disrupting the <it>TRY6 </it>gene to exemplify a quick and cheap genotyping approach for such structural variants. We showed that the deletion is larger than predicted and encompasses also the pseudogene <it>TRY5</it>. We performed a case-control study to test an association of the <it>TRY6 </it>deletion polymorphism with breast cancer using a single nucleotide polymorphism which is in 100% linkage disequilibrium with the deletion. We did not observe an effect of the deletion on breast cancer risk (OR 1.05, 95% CI 0.71–1.56).</p> <p>Conclusion</p> <p>Although we did not observe an association between the <it>TRY6 </it>deletion polymorphism and breast cancer risk, the identification and investigation of further deletions using the present approach may help to elucidate their effect on disease susceptibility.</p