ABSTRACT
BACKGROUND: ROS1 fusion is a relatively low prevalence (0.6-2.0%) but targetable driver in lung adenocarcinoma (LUAD). Robust and low-cost tests, such as immunohistochemistry (IHC), are desirable to screen for patients potentially harboring this fusion. The aim was to investigate the prevalence of ROS1 fusions in a clinically annotated European stage I-III LUAD cohort using IHC screening with the in vitro diagnostics (IVD)-marked clone SP384, followed by confirmatory molecular analysis in pre-defined subsets. METHODS: Resected LUADs constructed in tissue microarrays, were immunostained for ROS1 expression using SP384 clone in a ready-to-use kit and Ventana immunostainers. After external quality control, analysis was performed by trained pathologists. Staining intensity of at least 2+ (any percentage of tumor cells) was considered IHC positive (ROS1 IHC + ). Subsequently, ROS1 IHC + cases were 1:1:1 matched with IHC0 and IHC1 + cases and subjected to orthogonal ROS1 FISH and RNA-based testing. RESULTS: The prevalence of positive ROS1 expression (ROS1 IHC + ), defined as IHC 2+/3+, was 4 % (35 of 866 LUADs). Twenty-eight ROS1 IHC + cases were analyzed by FISH/RNA-based testing, with only two harboring a confirmed ROS1 gene fusion, corresponding to a lower limit for the prevalence of ROS1 gene fusion of 0.23 %. They represent a 7 % probability of identifying a fusion among ROS1 IHC + cases. Both confirmed cases were among the only four with sufficient material and H-score ≥ 200, leading to a 50 % probability of identifying a ROS1 gene fusion in cases with an H-score considered strongly positive. All matched ROS1 IHC- (IHC0 and IHC1 + ) cases were also found negative by FISH/RNA-based testing, leading to a 100 % probability of lack of ROS1 fusion for ROS1 IHC- cases. CONCLUSIONS: The prevalence of ROS1 fusion in an LUAD stage I-III European cohort was relatively low. ROS1 IHC using SP384 clone is useful for exclusion of ROS1 gene fusion negative cases.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Neoplasm Staging , Protein-Tyrosine Kinases , Proto-Oncogene Proteins , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Lung Neoplasms/surgery , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/surgery , Adenocarcinoma of Lung/metabolism , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/metabolism , Male , Female , Protein-Tyrosine Kinases/genetics , Protein-Tyrosine Kinases/metabolism , Middle Aged , Aged , Immunohistochemistry , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Europe , Oncogene Proteins, Fusion/genetics , Oncogene Proteins, Fusion/metabolism , Adult , In Situ Hybridization, FluorescenceABSTRACT
Thyroid cancer (TC) is a neoplasm with an increasing incidence worldwide. Its etiology is complex and based on a multi-layered interplay of factors. Among these, disorders of lipid metabolism have emerged as an important area of investigation. Cancer cells are metabolically reprogrammed to promote their rapid growth, proliferation, and survival. This reprogramming is associated with significant changes at the level of lipids, mainly fatty acids (FA), as they play a critical role in maintaining cell structure, facilitating signaling pathways, and providing energy. These lipid-related changes help cancer cells meet the increased demands of continued growth and division while adapting to the tumor microenvironment. In this review, we examine lipid metabolism at different stages, including synthesis, transport, and oxidation, in the context of TC and the effects of obesity and hormones on TC development. Recent scientific efforts have revealed disturbances in lipid homeostasis that are specific to thyroid cancer, opening up potential avenues for early detection and targeted therapeutic interventions. Understanding the intricate metabolic pathways involved in FA metabolism may provide insights into potential interventions to prevent cancer progression and mitigate its effects on surrounding tissues.
Subject(s)
Lipid Metabolism , Thyroid Neoplasms , Humans , Thyroid Neoplasms/metabolism , Thyroid Neoplasms/pathology , Thyroid Neoplasms/etiology , Lipid Metabolism Disorders/metabolism , Animals , Fatty Acids/metabolism , Tumor Microenvironment , Signal Transduction , Obesity/metabolismABSTRACT
Male sex is a risk factor for colorectal cancer (CRC) with higher illness burden and earlier onset. Thus, we hypothesized that loss of chromosome Y (LOY) in the tumor micro-environment (TME) might be involved in oncogenesis. Previous studies show that LOY in circulating leukocytes of aging men was associated with shorter survival and non-hematological cancer, as well as higher LOY in CD4 + T-lymphocytes in men with prostate cancer vs. controls. However, nothing is known about LOY in leukocytes infiltrating TME and we address this aspect here. We studied frequency and functional effects of LOY in blood, TME and non-tumorous tissue. Regulatory T-lymphocytes (Tregs) in TME had the highest frequency of LOY (22%) in comparison to CD4 + T-lymphocytes and cytotoxic CD8 + T-lymphocytes. LOY score using scRNA-seq was also linked to higher expression of PDCD1, TIGIT and IKZF2 in Tregs. PDCD1 and TIGIT encode immune checkpoint receptors involved in the regulation of Tregs function. Our study sets the direction for further functional research regarding a probable role of LOY in intensifying features related to the suppressive phenotype of Tregs in TME and consequently a possible influence on immunotherapy response in CRC patients.
Subject(s)
Colorectal Neoplasms , Liver Neoplasms , T-Lymphocytes, Regulatory , Tumor Microenvironment , Humans , Colorectal Neoplasms/pathology , Colorectal Neoplasms/immunology , Colorectal Neoplasms/genetics , Tumor Microenvironment/immunology , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , Male , Liver Neoplasms/immunology , Liver Neoplasms/secondary , Liver Neoplasms/pathology , Liver Neoplasms/genetics , Aged , Programmed Cell Death 1 Receptor/metabolism , Programmed Cell Death 1 Receptor/genetics , Middle Aged , Receptors, Immunologic/metabolism , Receptors, Immunologic/genetics , Female , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Ikaros Transcription Factor/genetics , Ikaros Transcription Factor/metabolismABSTRACT
AIM OF THE STUDY: To evaluate the long-term retention rate, efficacy, and tolerability of adjunctive cenobamate (CNB) in patients with drug-resistant epilepsy within the Polish Expanded Access Programme (EAP). CLINICAL RATIONALE FOR THE STUDY: Long-term retention rate is a useful measure of effectiveness including efficacy, safety, and tolerability of antiseizure medications. MATERIAL AND METHODS: We conducted a multicentre retrospective analysis of consecutive patients with focal epilepsy treated with CNB in the EAP between January 2020 and May 2023. All patients who completed the open-label extension phases of the YKP3089C013 and YKP3089C017 trials were offered the opportunity to continue CNB treatment within the EAP. We analysed cenobamate retention, seizure outcomes, and adverse events. RESULTS: 38 patients (18 females; 47.3%) continued CNB treatment within the Expanded Access Programme for 41 months. The mean baseline age of patients was 39.3 years (range: 18-57). All patients were on polytherapy, with the most commonly used antiseizure medications being valproate, levetiracetam, and carbamazepine. Adjunctive CNB treatment resulted in a reduced mean seizure frequency from 8.1 seizures (range: 4-20) per month to 3 seizures (range: 0-8) per month. At the final follow-up, the median CNB dose was 200 mg/day (range: 50-350). Among the patients, 24 (63.1%) achieved ≥ 50% seizure reduction, and eight (21%) remained seizure-free for at least 12 months. One in three patients experienced adverse events, which resolved in half of the subjects. The most frequent adverse events were dizziness, somnolence, and headache. The retention rate after completing the open-label extension phase was 100%. CONCLUSIONS AND CLINICAL IMPLICATIONS: Long-term effectiveness, including ≥ 50% seizure reduction and a 100% retention rate, was sustained over 41 months of CNB treatment within the Expanded Access Programme. No new safety issues were identified. These results provide support for the potential long-term clinical benefits of cenobamate.
Subject(s)
Anticonvulsants , Seizures , Adolescent , Adult , Female , Humans , Middle Aged , Young Adult , Anticonvulsants/therapeutic use , Drug Therapy, Combination , Retrospective Studies , Treatment OutcomeABSTRACT
INTRODUCTION: COVID-19 is a disease characterized by high in-hospital mortality, which seems to be dependent on many predisposing factors. OBJECTIVES: The aim of this study was to analyze the clinical symptoms, abnormalities in the results of laboratory tests, and coexisting chronic diseases that independently affected the risk of in-hospital mortality in patients with COVID-19. PATIENTS AND METHODS: We analyzed the records of patients with COVID-19 who were hospitalized from 6 March 2020 to 30 November 2021. RESULTS: Out of the entire group of 2138 patients who were analyzed, 12.82% died during hospitalization. In-hospital mortality was independently associated with older age (OR 1.53, 95% CI 1.20-1.97); lower arterial blood oxygen saturation (OR 0.95, 95% CI 0.92-0.99); the presence of a neoplasm (OR 4.45, 95% CI 2.01-9.62), a stomach ulcer (OR 3.35, 95% CI 0.94-11.31), and dementia (OR 3.40, 95% CI 1.36-8.26); a higher score on the SOFA scale (OR 1.73, 95% CI 1.52-1.99); higher lactate dehydrogenase (LDH) (OR 1.08, 95% CI 1.05-1.12); higher N-terminal pro-brain natriuretic peptide (NT pro BNP) (OR 1.06, 95% CI 1.01-1.11); and lower total bilirubin in blood concentration (OR 0.94, 95% CI 0.90-0.99). CONCLUSIONS: We found that low oxygen saturation, old age, and the coexistence of cancer, gastric ulcers, and dementia syndrome were variables that independently increased mortality during hospitalization due to COVID-19. Moreover, we found that decreased platelet count and bilirubin concentration and increased levels of LDH and NT-proBNP were laboratory test results that independently indicated a higher risk of mortality. We also confirmed the usefulness of the SOFA scale in predicting treatment results. The ability to identify mortality risk factors on admission to hospital will facilitate both adjusting the intensity of treatment and the monitoring of patients infected with SARS-CoV-2.
ABSTRACT
Mpox has become the most significant orthopoxviral infection among humans. Since May 2022, there has been a multicountry outbreak of mpox across six continents. Retrospective observational cohort study of 94 patients with probable or confirmed mpox of whom 86.2% were hospitalized in Hospital for Infectious Diseases in Warsaw, Poland between May 16 and October 30, 2022. Most patients were young (median age: 31, IQR: 25-43 years), predominantly (88.3%) Polish men who have sex with men exposed most commonly in Poland (82.7%), Spain (6.2%), or Germany (4.9%). The median observed mpox incubation period was 7 (IQR: 4-8) days with the median hospitalization time of 7 (range: 2-24, IQR: 5-11) days. History of sexually transmitted infections (STIs) was common in the group (previous syphilis or hepatitis C virus in 33.3% and 17.3%, respectively, 6.2% of early syphilis or gonorrhea). A significant proportion (n = 43, 45.7%) of mpox cases were people with human immunodeficiency virus (HIV), all except one were on stable and virologically effective (88.4% with HIV viral load <50 copies/mL) antiretroviral treatment. Chemsex was reported in 34.6% of hospitalized cases, more commonly among people with HIV (48.5% vs. 25.0%, p = 0.029). None of the mpox infected patients presented with advanced HIV infection. Despite the fact that 6.3% of cases presented with >50 skin lesions the course of the disease was self-limited with no severe cases or deaths. There were no significant clinical or laboratory differences or complication rates between patients with and without HIV coinfection. Epidemiological and clinical characteristics of mpox in Poland are similar to other countries, but there were no targeted, population oriented interventions or vaccination programs. Mpox diagnosis provided an opportunity to screen and diagnose other STIs. As Central European populations, including refugees from Ukraine, are largely unvaccinated against mpox access to preventive vaccinations and antiviral therapy should be maximized.
Subject(s)
HIV Infections , HIV Seropositivity , Mpox (monkeypox) , Sexual and Gender Minorities , Sexually Transmitted Diseases , Syphilis , Male , Humans , Adult , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Syphilis/complications , Homosexuality, Male , Retrospective Studies , Sexually Transmitted Diseases/epidemiology , Europe , Disease ProgressionABSTRACT
BACKGROUND: Angiomatoid fibrous histiocytoma (AFH) is a rare, slow-growing soft tissue tumor. It appears mostly on the limbs and trunk in children and young adults. The biology of AFH remains unclear because of the small number of reported cases. Diagnostic testing does not provide definitive results. It has two clinical forms, that differ in terms of gene expression and clinical prognosis. It is important to inform the laboratory which specific gene testing is necessary. Here, we describe a case of rare AFH in the submandibular region using a full genetic panel. CASE SUMMARY: A 13-year-old boy who had been misdiagnosed in the past 6 mo by his dentist visited our clinic because of a lesion in the submandibular area on the right side. The lesion was homogeneous and painless upon palpation. No skin discoloration was observed. Due to the non-specific radiological picture computed tomography (CT), magnetic resonance imaging (MRI), cone-beam CT (CBCT), and ultrasound-guided biopsy were performed. A venous malformation was suspected on the MRI. None of the tests provided a definitive diagnosis. Owing to the non-specific radiological findings, the patient qualified for surgical treatment. The surgical procedure included an excisional biopsy. The diagnostic testing was extended using gene rearrangements. The most distinctive gene translocation in diagnosing AFH is within the EWS RNA-binding protein 1 (EWSR1)-CREB-binding protein. However, in this case, the diagnosis was confirmed by a rearrangement within the EWSR1 gene testing. CONCLUSION: AFH in the submandibular location is rare, and surgical treatment with genetic evaluation defines AFH type that affects subsequent procedures.
ABSTRACT
Tick-borne encephalitis (TBE) is a central nervous system zoonotic disease transmitted by ticks. Tick-borne encephalitis virus (TBEV) is one of the main causes of lymphocytic meningitis in the areas of its endemic occurrence. A mode of transmission of TBEV which is rarely observed in clinical practice is an alimentary transmission through consumption of unpasteurised dairy products from infected animals. The following article contains detailed description of the clinical course of TBE among five family members, for whom the occurrence of TBE was temporarily associated with the consumption of unpasteurised goat's milk from the same source. The epidemiological outbreak presented in this article is the fifth ever described case of the milk-borne TBE in Poland. More so, the clinical course of the disease has shown differences from the typical course characterised so far in the literature. Clinical cases of TBE described in this study were similar to infections caused by tick bites in humans. The following article discusses available methods of preventing TBE, with emphasis on alimentary transmission of TBEV, since possibility of serious detrimental long-term neurological complications resulting from TBE was stressed in prior literature.
Subject(s)
Encephalitis Viruses, Tick-Borne , Encephalitis, Tick-Borne , Ticks , Animals , Humans , Poland/epidemiology , Milk , Encephalitis, Tick-Borne/epidemiology , Encephalitis, Tick-Borne/prevention & control , Disease ProgressionSubject(s)
Choristoma , Thymoma , Thymus Neoplasms , Humans , Thyroid Gland/diagnostic imaging , Thyroid Gland/surgery , Thyroid Gland/pathology , Thymoma/diagnostic imaging , Thymoma/surgery , Choristoma/pathology , Ultrasonography , Thymus Neoplasms/diagnostic imaging , Thymus Neoplasms/surgery , Thymus Neoplasms/pathologyABSTRACT
Monkeypox is a viral, zoonotic, emerging infectious disease that has become the most significant orthopoxviral infection among humans since the eradication of smallpox. It is endemic in Central and West Africa, and since May 2022 it has caused a multi-country outbreak in six continents. So far, no clinical cases of this disease have been observed in Poland. Monkeypox can be transmitted by any person, regardless of gender identity or sexual preferences, through direct contact with the secretion from skin lesions or through fomites contaminated with infectious material. Therefore, people infected with the monkeypox virus require isolation until the skin lesions heal completely and the scabs fall off, which is equivalent to the end of their infectivity. The paper presents a study of the first nine clinical cases of monkeypox in Poland, along with photographic documentation. All patients were young men, the vast majority of whom had contact with multiple sexual partners, and presented a higher prevalence of human immunodeficiency virus (HIV) infection than in the general population. The course of the disease was self-limited and no specific antiviral treatment was required by any of the patients. Nonetheless, there was a change in the route of transmission of the infection to sexual contact and an atypical clinical course of the disease, which resulted both in skin lesions initially appearing in the anogenital area, skin lesions occurring at various stages of development, and the appearance of skin lesions before the onset of general symptoms. In one of the patients, skin changes were not observed at all.
Subject(s)
Mpox (monkeypox) , Antiviral Agents , Female , Gender Identity , Humans , Male , Mpox (monkeypox)/diagnosis , Mpox (monkeypox)/epidemiology , Monkeypox virus , Poland/epidemiologyABSTRACT
Inflammatory bowel disease (IBD) is a group of chronic inflammatory disorders of the gastrointestinal tract with worldwide increasing incidence. Recent studies indicate that certain species of intestinal bacteria are strongly associated with IBD. Helper T lymphocytes are not only the key players in mediating host defense against a wide variety of pathogens but also contribute to pathogenesis of many immune-related diseases. Here, using the T cell transfer model of colitis, we observed that the mice maintained in a specific-pathogen free (SPF) unit after receiving naïve CD4+ T cells developed mild disease. The same mice developed different degrees of disease when they were maintained in a conventional animal facility (non-SPF), where some pathogens were detected during routine health monitoring. Consistently, increased circulating inflammatory cytokines as well as Th1 and Th17 cells were detected in mice housed in non-SPF units. 16S rRNA sequencing of feces samples enabled us to identify changes in the microbiota composition of mice kept in different facilities. Our data indicate that environmental factors influence gut microbiota composition of mice, leading to development of colitis in a T-cell-dependent manner. In conclusion, changes in environmental conditions and microbial status of experimental animals appear to contribute to progression of colitis.
Subject(s)
Colitis , Gastrointestinal Microbiome , Inflammatory Bowel Diseases , Mice , Animals , RNA, Ribosomal, 16S/genetics , Mice, Inbred C57BL , Disease Models, Animal , Colitis/pathology , Inflammatory Bowel Diseases/complicationsABSTRACT
The progress in translational cancer research relies on access to well-characterized samples from a representative number of patients and controls. The rationale behind our biobanking are explorations of post-zygotic pathogenic gene variants, especially in non-tumoral tissue, which might predispose to cancers. The targeted diagnoses are carcinomas of the breast (via mastectomy or breast conserving surgery), colon and rectum, prostate, and urinary bladder (via cystectomy or transurethral resection), exocrine pancreatic carcinoma as well as metastases of colorectal cancer to the liver. The choice was based on the high incidence of these cancers and/or frequent fatal outcome. We also collect age-matched normal controls. Our still ongoing collection originates from five clinical centers and after nearly 2-year cooperation reached 1711 patients and controls, yielding a total of 23226 independent samples, with an average of 74 donors and 1010 samples collected per month. The predominant diagnosis is breast carcinoma, with 933 donors, followed by colorectal carcinoma (383 donors), prostate carcinoma (221 donors), bladder carcinoma (81 donors), exocrine pancreatic carcinoma (15 donors) and metachronous colorectal cancer metastases to liver (14 donors). Forty percent of the total sample count originates from macroscopically healthy cancer-neighboring tissue, while contribution from tumors is 12%, which adds to the uniqueness of our collection for cancer predisposition studies. Moreover, we developed two program packages, enabling registration of patients, clinical data and samples at the participating hospitals as well as the central system of sample/data management at coordinating center. The approach used by us may serve as a model for dispersed biobanking from multiple satellite hospitals. Our biobanking resource ought to stimulate research into genetic mechanisms underlying the development of common cancers. It will allow all available "-omics" approaches on DNA-, RNA-, protein- and tissue levels to be applied. The collected samples can be made available to other research groups.
Subject(s)
Breast Neoplasms , Carcinoma , Colorectal Neoplasms , Biological Specimen Banks , Breast Neoplasms/genetics , Genetic Variation , Humans , Male , Mastectomy , Pancreatic Neoplasms , Pancreatic NeoplasmsABSTRACT
Langerhans cell histiocytosis (LCH) is a rare inflammatory disorder of myeloid dendritic cells with mutations involving KRAS, BRAF and/or NRAS, and MAP2K1 genes. We describe the case of a 58-year-old female previous smoker with multifocal LCH involving the lungs, pituitary gland and mandibular bone. Initial treatment with 6 cycles of cladribine showed improvement in her extrapulmonary lesions, however, her lung disease progressed and after qualification and assessment tests she underwent uncomplicated double lung transplant surgery and was discharged home. We highlight that in select patients with well managed and controlled extrapulmonary LCH, such an invasive procedure as lung transplant is possible.
Subject(s)
Histiocytosis, Langerhans-Cell , Lung Transplantation , Cladribine/therapeutic use , Female , Histiocytosis, Langerhans-Cell/diagnosis , Histiocytosis, Langerhans-Cell/drug therapy , Histiocytosis, Langerhans-Cell/pathology , Humans , Lung Transplantation/adverse effects , Middle Aged , Mutation , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins B-raf/metabolism , Proto-Oncogene Proteins B-raf/therapeutic useABSTRACT
BACKGROUND: The association between COVID-19 infection and the development of autoimmune diseases is currently unknown, but there are already reports presenting induction of different autoantibodies by SARS-CoV-2 infection. Kikuchi-Fuimoto disease (KFD) as a form of histiocytic necrotizing lymphadenitis of unknown origin. OBJECTIVE: Here we present a rare case of KFD with heart involvement after COVID-19 infection. To our best knowledge only a few cases of COVID-19-associated KFD were published so far. Based on presented case, we summarize the clinical course of KFD and its association with autoimmune diseases, as well we discuss the potential causes of perimyocarditis in this case. METHODS: We reviewed the literature regarding cases of "Kikuchi-Fujimoto disease (KFD)" and "COVID-19" and then "KFD" and "heart" or "myocarditis" by searching medical journal databases written in English in PubMed and Google Scholar. RESULTS: Only two cases of KFD after COVID infection have been described so far. CONCLUSION: SARS-CoV-2 infection can also be a new, potential causative agent of developing KFD.
Subject(s)
COVID-19/physiopathology , Hepatomegaly/physiopathology , Histiocytic Necrotizing Lymphadenitis/physiopathology , Myocarditis/physiopathology , Splenomegaly/physiopathology , Ventricular Dysfunction, Left/physiopathology , Adult , COVID-19/complications , COVID-19 Nucleic Acid Testing , COVID-19 Serological Testing , Echocardiography , Hepatomegaly/diagnostic imaging , Hepatomegaly/etiology , Histiocytic Necrotizing Lymphadenitis/etiology , Histiocytic Necrotizing Lymphadenitis/pathology , Humans , Male , Myocarditis/diagnostic imaging , Myocarditis/etiology , SARS-CoV-2 , Splenomegaly/diagnostic imaging , Splenomegaly/etiology , Stroke Volume , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/etiologySubject(s)
Cardiomyopathies , Autopsy , Cardiomyopathies/genetics , Death, Sudden, Cardiac/etiology , Humans , Lamin Type A/genetics , Mutation , PedigreeABSTRACT
Better understanding of GBM signalling networks in-vivo would help develop more physiologically relevant ex vivo models to support therapeutic discovery. A "functional proteomics" screen was undertaken to measure the specific activity of a set of protein kinases in a two-step cell-free biochemical assay to define dominant kinase activities to identify potentially novel drug targets that may have been overlooked in studies interrogating GBM-derived cell lines. A dominant kinase activity derived from the tumour tissue, but not patient-derived GBM stem-like cell lines, was Bruton tyrosine kinase (BTK). We demonstrate that BTK is expressed in more than one cell type within GBM tissue; SOX2-positive cells, CD163-positive cells, CD68-positive cells, and an unidentified cell population which is SOX2-negative CD163-negative and/or CD68-negative. The data provide a strategy to better mimic GBM tissue ex vivo by reconstituting more physiologically heterogeneous cell co-culture models including BTK-positive/negative cancer and immune cells. These data also have implications for the design and/or interpretation of emerging clinical trials using BTK inhibitors because BTK expression within GBM tissue was linked to longer patient survival.
Subject(s)
Agammaglobulinaemia Tyrosine Kinase/metabolism , Brain Neoplasms/enzymology , Brain Neoplasms/mortality , Glioblastoma/enzymology , Glioblastoma/mortality , Proteome/metabolism , Signal Transduction , Brain Neoplasms/pathology , Cell Line, Tumor , Cell Survival , Coculture Techniques/methods , Glioblastoma/pathology , Humans , Neoplastic Stem Cells/enzymology , Proteomics/methods , SOXB1 Transcription Factors/metabolism , Survival RateABSTRACT
BACKGROUND: The first description of performing a new diagnostic procedure, cryobiopsy, in lung transplant recipients in Poland. METHODS: Three cases of patients after lung transplantation were analyzed in context of the procedure of cryobiopsy, which was performed in a hybrid room with a bronchoscopic video track and C-arm radiograph. Patients were subjected to complete anesthesia and intubated. Two or three sections with an average diameter of 5 mm were collected. RESULTS: The sections were large and fully diagnostic. In all 3 described cases they brought a decisive element into diagnosis. CONCLUSIONS: Cryobiopsy is a useful tool in the differential diagnosis of lesions and complications that occur after lung transplantation.
Subject(s)
Lung Transplantation , Biopsy , Bronchoscopy , Follow-Up Studies , Humans , Lung/diagnostic imaging , Lung Diseases, Interstitial , Lung Transplantation/adverse effects , Retrospective StudiesABSTRACT
RNA editing is one of the most prevalent and abundant forms of post-transcriptional RNA modification observed in normal physiological processes and often aberrant in diseases including cancer. RNA editing changes the sequences of mRNAs, making them different from the source DNA sequence. Edited mRNAs can produce editing-recoded protein isoforms that are functionally different from the corresponding genome-encoded protein isoforms. The major type of RNA editing in mammals occurs by enzymatic deamination of adenosine to inosine (A-to-I) within double-stranded RNAs (dsRNAs) or hairpins in pre-mRNA transcripts. Enzymes that catalyse these processes belong to the adenosine deaminase acting on RNA (ADAR) family. The vast majority of knowledge on the RNA editing landscape relevant to human disease has been acquired using in vitro cancer cell culture models. The limitation of such in vitro models, however, is that the physiological or disease relevance of results obtained is not necessarily obvious. In this review we focus on discussing in vivo occurring RNA editing events that have been identified in human cancer tissue using samples surgically resected or clinically retrieved from patients. We discuss how RNA editing events occurring in tumours in vivo can identify pathological signalling mechanisms relevant to human cancer physiology which is linked to the different stages of cancer progression including initiation, promotion, survival, proliferation, immune escape and metastasis.
Subject(s)
Adenosine/genetics , Carcinogenesis/pathology , Inosine/genetics , Neoplasms/pathology , RNA Editing , RNA, Double-Stranded/genetics , RNA-Binding Proteins/metabolism , Animals , Carcinogenesis/genetics , Humans , Neoplasms/genetics , Neoplasms/metabolism , RNA-Binding Proteins/geneticsABSTRACT
Microphthalmia-associated transcription factor renal cell cancer, also known as translocation renal cell cancer, belongs to the group of extremely rare non-clear-cell kidney neoplasms. Their incidence is lower in adulthood than in childhood. The only known risk factor for the development of this tumor is prior chemotherapy. In the operable stage of the disease, the prognosis depends on the status of regional lymph nodes. Interestingly lymph node positivity worsens the prognosis only in the adult patient population. Radical surgical excision is the best therapy in the early stage. The optimal treatment strategy for locally advanced and metastatic disease has not been established, given the lack of evidence in such a rare disease. We present the case of a patient with an aggressive course of this neoplasm treated with temsirolimus, who achieved 10-month control of this neoplasm accompanied by a discussion on other therapeutic possibilities.
ABSTRACT
Eosinophilic fasciitis is a rare connective tissue disease of unknown etiology. Therapeutic options include high-dose corticosteroids and other immunosuppressive drugs. We present a typical eosinophilic fasciitis case, which did not respond to first-line treatment, but improved remarkably after infliximab administration. This report demonstrates that in case of initial treatment failure, infliximab might be a relatively safe and effective way of eosinophilic fasciitis management.