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1.
Int J Mol Sci ; 21(15)2020 Jul 24.
Article in English | MEDLINE | ID: mdl-32722130

ABSTRACT

Colorectal cancer (CRC) remains a serious health problem worldwide. Approximately half of patients will develop distant metastasis after CRC resection, usually with very poor prognosis afterwards. Because patient performance after distant metastasis surgery remains very heterogeneous, ranging from death within 2 years to a long-term cure, there is a clinical need for a precise risk stratification of patients to aid pre- and post-operative decisions. Furthermore, around 20% of identified CRC cases are at IV stage disease, known as a metastatic CRC (mCRC). In this review, we overview possible molecular and clinicopathological biomarkers that may provide prognostic and predictive information for patients with distant metastasis. These may comprise sidedness of the tumor, molecular profile and epigenetic characteristics of the primary tumor and arising metastatic CRC, and early markers reflecting cancer cell resistance in mCRC and biomarkers identified from transcriptome. This review discusses current stage in employment of these biomarkers in clinical practice as well as summarizes current experience in identifying predictive biomarkers in mCRC treatment.


Subject(s)
Biomarkers, Tumor/biosynthesis , Colorectal Neoplasms , Epigenesis, Genetic , Gene Expression Regulation, Neoplastic , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Colorectal Neoplasms/therapy , Humans , Neoplasm Metastasis
2.
J Cell Mol Med ; 23(8): 5728-5736, 2019 08.
Article in English | MEDLINE | ID: mdl-31207084

ABSTRACT

The primary cilium is considered as a key component of morphological cellular stability. However, cancer cells are notorious for lacking primary cilia in most cases, depending upon the tumour type. Previous reports have shown the effect of starvation and cytostatics on ciliogenesis in normal and cancer cells although with limited success, especially when concerning the latter. In this study, we evaluated the presence and frequency of primary cilia in breast fibroblasts and in triple-negative breast cancer cells after treatment with cytostatics finding that, in the case of breast fibroblasts, primary cilia were detected at their highest incidence 72 hours after treatment with 120 nM doxorubicin. Further, multiciliated cells were also detected after treatment with 80 nM doxorubicin. On the other hand, treatment with taxol increased the number of ciliated cells only at low concentrations (1.25 and 3.25 nM) and did not induce multiciliation. Interestingly, triple-negative breast cancer cells did not present primary cilia after treatment with either doxorubicin or taxol. This is the first study reporting the presence of multiple primary cilia in breast fibroblasts induced by doxorubicin. However, the null effect of these cytostatics on primary cilia incidence in the evaluated triple negative breast carcinomas cell lines requires further research.


Subject(s)
Cilia/metabolism , Cytostatic Agents/toxicity , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Cilia/drug effects , Doxorubicin/pharmacology , Fibroblasts/drug effects , Fibroblasts/metabolism , Humans , Paclitaxel/pharmacology
3.
J BUON ; 22(6): 1477-1487, 2017.
Article in English | MEDLINE | ID: mdl-29332341

ABSTRACT

PURPOSE: Primary cilium (PC) is considered to be a functional homologue of the immune synapse. Microtubule structures, PC of cancer associated fibroblasts and immune synapses between cytotoxic CD8+ tumor infiltrating lymphocytes (TILs) and cancer cells, are regularly found in varying amounts in the microenvironment of solid tumors. The purpose of this study was to find out the potential association and combined prognostic significance of the frequency of PC, PD-1 and CD8+ TILs in patients with intestinal cancer. METHODS: The frequency of PC, programmed cell death protein-1 receptor (PD-1) expression and the frequency of stromal and intraepithelial CD8+TILs were evaluated in samples of colorectal adenocarcinoma (32 patiens) and small bowel cancer (8 patients). RESULTS: The median frequency of PC was 0.25%. The expression of PD1 was <5% in 34 patients, 5-25% in 5 patients and 26-50% in 1 patient. The frequency of stromal CD8+ TILs was negative in 3 patients, <25% in 26, 26-50% in 10 and >50% in 1 patient, respectively. Intraepithelial CD8+ TILs were not detectable in 14, <25% in 24 and 26-50% in 2 patients, respectively. Statistically, the frequency of PC and PD-1 positivity were significantly associated (p=0.004). An association between the PC frequency and intraepithelial CD8+ TILs was of borderline statistical significance (p=0.059). An index combining the frequency of PC and stromal CD8+ TILs, but not the combination of frequency of PC and intraepithelial CD8+ TILs, was of borderline prognostic significance (p=0.067). CONCLUSIONS: The present study provides the first data on the potential association and combined prognostic significance of frequency of PC, PD-1 and CD8+ TILs in patients with intestinal cancer.


Subject(s)
CD8-Positive T-Lymphocytes/metabolism , Cilia/pathology , Intestinal Neoplasms/genetics , Programmed Cell Death 1 Receptor/metabolism , Aged , Female , Humans , Intestinal Neoplasms/metabolism , Intestinal Neoplasms/pathology , Male , Middle Aged , Prognosis , Retrospective Studies
4.
J BUON ; 21(5): 1233-1241, 2016.
Article in English | MEDLINE | ID: mdl-27837628

ABSTRACT

PURPOSE: The primary cilium is a solitary, sensory, immotile microtubule-based structure that arises from the centrosome and is projected from the surface of most human cell types. It has been hypothesized that primary cilia could serve as a tumor suppressor organelle. The objective of this pilot study was to investigate the presence and frequency of primary cilia in cells of small bowel and colorectal adenocarcinoma and to evaluate the prognostic significance of their frequency. METHODS: The presence of primary cilia in cells in samples of small bowel (8 patients) and colorectal adenocarcinoma (32 patients) was evaluated. The primary cilia of cells were immunofluorescently labeled using primary monoclonal anti-acetylated agr;-tubulin antibody and cell nuclei were labeled using DAPI. RESULTS: Primary cilia were identified in all examined specimens. The median frequency of primary cilia was 0.49% in cells of small bowel cancer and 0.22% in cells in colorectal cancer. Overall survival according to frequency of primary cilia in all intestinal adenocarcinomas was significantly longer in patients with higher frequency (≥ 0.187) than in patients with lower frequency of primary cilia (< 0.187) in univariate analysis (p=0.007) and also in the Cox proportional hazard model (p=0.032). Overall survival according to frequency of primary cilia in colorectal adenocarcinoma was significantly longer in patients with higher frequency (≥ 0.187) than in patients with lower frequency of primary cilia (< 0.187) (p=0.028). CONCLUSIONS: The present pilot study provides the first evidence of the prognostic significance of the frequency of primary cilia in small bowel and colorectal adenocarcinoma. Because of significantly higher median frequency of primary cilia in the rare small bowel adenocarcinoma than in the frequent colorectal adenocarcinoma (p<0.001), the results of this study support a potential role for primary cilia as a biomarker in these types of cancer.


Subject(s)
Adenocarcinoma/pathology , Colorectal Neoplasms/pathology , Intestinal Neoplasms/pathology , Intestine, Small/pathology , Acetylation , Adenocarcinoma/chemistry , Adenocarcinoma/mortality , Aged , Aged, 80 and over , Area Under Curve , Biomarkers, Tumor/analysis , Cilia/chemistry , Cilia/pathology , Colorectal Neoplasms/chemistry , Colorectal Neoplasms/mortality , Female , Fluorescent Antibody Technique , Humans , Intestinal Neoplasms/chemistry , Intestinal Neoplasms/mortality , Intestine, Small/chemistry , Kaplan-Meier Estimate , Male , Middle Aged , Pilot Projects , Predictive Value of Tests , Prognosis , Proportional Hazards Models , ROC Curve , Retrospective Studies , Risk Factors , Time Factors , Tubulin/analysis
5.
Acta Medica (Hradec Kralove) ; 58(1): 3-8, 2015.
Article in English | MEDLINE | ID: mdl-26454800

ABSTRACT

Ovarian cancer is the fifth most common malignancy in the world's female population and with the highest lethality index among gynecological tumors. The prognosis of metastatic disease is usually poor, especially in platinum-resistant cases. There are several options for the treatment of metastatic disease resistant to platinum derivates (e.g. paclitaxel, topotecan and pegylated liposomal doxorubicin), all of which are considered equipotent. Pegylated liposomal doxorubicin (PLD) is a liposomal form of the anthracycline antibiotic doxorubicin. It is characterized by more convenient pharmacokinetics and a different toxicity profile. Cardiotoxicity, the major adverse effect of conventional doxorubicin, is reduced in PLD as well as hematotoxicity, alopecia, nausea and vomiting. Skin toxicity and mucositis, however, emerge as serious issues since they represent dose and schedule-limiting toxicities. The pharmacokinetics of PLD (prolonged biological half-life and preferential distribution into tumor tissue) provide new possibilities to address these toxicity issues. The extracorporeal elimination of circulating liposomes after PLD saturation in the tumor tissue represents a novel and potent strategy to diminish drug toxicity. This article intends to review PLD characteristics and the importance of extracorporeal elimination to enhance treatment tolerance and benefits.


Subject(s)
Antibiotics, Antineoplastic/blood , Antibiotics, Antineoplastic/therapeutic use , Doxorubicin/analogs & derivatives , Extracorporeal Circulation , Ovarian Neoplasms/blood , Ovarian Neoplasms/drug therapy , Cytostatic Agents , Doxorubicin/blood , Doxorubicin/therapeutic use , Drug Resistance, Neoplasm , Female , Humans , Platinum Compounds/therapeutic use , Polyethylene Glycols/therapeutic use
6.
J Cell Mol Med ; 18(5): 832-43, 2014 May.
Article in English | MEDLINE | ID: mdl-24444357

ABSTRACT

Bone marrow-derived cells represent a heterogeneous cell population containing haematopoietic stem and progenitor cells. These cells have been identified as potential candidates for use in cell therapy for the regeneration of damaged tissues caused by trauma, degenerative diseases, ischaemia and inflammation or cancer treatment. In our study, we examined a model using whole-body irradiation and the transplantation of bone marrow (BM) or haematopoietic stem cells (HSCs) to study the repair of haematopoiesis, extramedullary haematopoiesis and the migration of green fluorescent protein (GFP(+)) transplanted cells into non-haematopoietic tissues. We investigated the repair of damage to the BM, peripheral blood, spleen and thymus and assessed the ability of this treatment to induce the entry of BM cells or GFP(+) lin(-) Sca-1(+) cells into non-haematopoietic tissues. The transplantation of BM cells or GFP(+) lin(-) Sca-1(+) cells from GFP transgenic mice successfully repopulated haematopoiesis and the haematopoietic niche in haematopoietic tissues, specifically the BM, spleen and thymus. The transplanted GFP(+) cells also entered the gastrointestinal tract (GIT) following whole-body irradiation. Our results demonstrate that whole-body irradiation does not significantly alter the integrity of tissues such as those in the small intestine and liver. Whole-body irradiation also induced myeloablation and chimerism in tissues, and induced the entry of transplanted cells into the small intestine and liver. This result demonstrates that grafted BM cells or GFP(+) lin(-) Sca-1(+) cells are not transient in the GIT. Thus, these transplanted cells could be used for the long-term treatment of various pathologies or as a one-time treatment option if myeloablation-induced chimerism alone is not sufficient to induce the entry of transplanted cells into non-haematopoietic tissues.


Subject(s)
Bone Marrow Cells/cytology , Bone Marrow Transplantation , Chimerism , Gastrointestinal Tract/physiology , Hematopoietic Stem Cell Transplantation , Regeneration , Whole-Body Irradiation , Animals , DNA/metabolism , Flow Cytometry , Gastrointestinal Tract/cytology , Green Fluorescent Proteins/metabolism , Hematopoiesis , Hematopoietic Stem Cells/cytology , Intestine, Small/cytology , Intestine, Small/physiology , Liver/cytology , Mice, Inbred C57BL , Models, Biological
7.
Int J Mol Sci ; 15(1): 1647-70, 2014 Jan 22.
Article in English | MEDLINE | ID: mdl-24451143

ABSTRACT

Hair follicle morphogenesis depends on Wnt, Shh, Notch, BMP and other signaling pathways interplay between epithelial and mesenchymal cells. The Wnt pathway plays an essential role during hair follicle induction, Shh is involved in morphogenesis and late stage differentiation, Notch signaling determines stem cell fate while BMP is involved in cellular differentiation. The Wnt pathway is considered to be the master regulator during hair follicle morphogenesis. Wnt signaling proceeds through EDA/EDAR/NF-κB signaling. NF-κB regulates the Wnt pathway and acts as a signal mediator by upregulating the expression of Shh ligand. Signal crosstalk between epithelial and mesenchymal cells takes place mainly through primary cilia. Primary cilia formation is initiated with epithelial laminin-511 interaction with dermal ß-1 integrin, which also upregulates expression of downstream effectors of Shh pathway in dermal lineage. PDGF signal transduction essential for crosstalk is mediated through epithelial PDGF-A and PDGFRα expressed on the primary cilia. Dermal Shh and PDGF signaling up-regulates dermal noggin expression; noggin is a potent inhibitor of BMP signaling which helps in counteracting BMP mediated ß-catenin inhibition. This interplay of signaling between the epithelial and dermal lineage helps in epithelial Shh signal amplification. The dermal Wnt pathway helps in upregulation of epithelial Notch expression. Dysregulation of these pathways leads to certain abnormalities and in some cases even tumor outgrowth.


Subject(s)
Hair Follicle/growth & development , Morphogenesis , Signal Transduction , Animals , Hair Diseases/genetics , Hair Diseases/metabolism , Hair Follicle/metabolism , Humans
8.
Acta Medica (Hradec Kralove) ; 57(4): 142-50, 2014.
Article in English | MEDLINE | ID: mdl-25938897

ABSTRACT

High grade gliomas are some of the deadliest human tumours. Conventional treatments such as surgery, radiotherapy and chemotherapy have only a limited effect. Nowadays, resection is the common treatment of choice and although new approaches, such as perioperative magnetic resonance imaging or fluorescent microscopy have been developed, the survival rate of diagnosed patients is still very low. The inefficacy of conventional methods has led to the development of new strategies and the significant progress of nanotechnology in recent years. These platforms can be used either as novel imaging tools or to improve anticancer drug delivery into tumours while minimizing its distribution and toxicity in healthy tissues. Amongst the new nanotechnology platforms used for delivery into the brain tissue are: polymeric nanoparticles, liposomes, dendrimers, nanoshells, carbon nanotubes, superparamagnetic nanoparticles and nucleic acid based nanoparticles (DNA, RNA interference [RNAi] and antisense oligonucleotides [ASO]). These nanoparticles have been applied in the delivery of small molecular weight drugs as well as macromolecules - proteins, peptides and genes. The unique properties of these nanoparticles, such as surface charge, particle size, composition and ability to modify their surface with tissue recognition ligands and antibodies, improve their biodistribution and pharmacokinetics. All of the above mentioned characteristics make of nanoplatforms a very suitable tool for its use in targeted, personalized medicine, where they could possibly carry large doses of therapeutic agents specifically into malignant cells while avoiding healthy cells. This review poses new possibilities in the large field of nanotechnology with special interest in the treatment of high grade brain tumours.


Subject(s)
Brain Neoplasms/therapy , Nanotechnology/trends , Antineoplastic Agents/therapeutic use , Diagnostic Imaging , Drug Carriers , Drug Delivery Systems , Genetic Therapy , Genetic Vectors , Humans , Nanoparticles/therapeutic use , Nanotubes , Stem Cell Transplantation
9.
Eur J Orthop Surg Traumatol ; 24(3): 257-62, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24101189

ABSTRACT

Despite the undisputed modern development of synthetic biomaterials that range from bioactive unresorbable to restorable materials, clinically applied osteoconduction bone substitutes still have limitations in the treatment of bone defects. These are the result of the physical and chemical properties of the utilized materials and the biological interactions associated with both local and general reactions of the organism. Mesenchymal stem cells constitute a promising treatment alternative in orthopedics. Preclinical studies regarding the use of mesenchymal stem cells have shown good therapeutic results. However, it is still necessary to advance further in this area and enable the treatment of patients with critically large bone defects. The aim of this review is to describe the role of mesenchymal stem cells in bone repair and regeneration, describe the techniques used in the clinical application of mesenchymal stem cells and outline future research endeavors in this area.


Subject(s)
Bone Regeneration , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/physiology , Bone Diseases/therapy , Cell Differentiation , Humans , Tissue Engineering
10.
BMJ Support Palliat Care ; 13(e3): e1308-e1317, 2024 Jan 08.
Article in English | MEDLINE | ID: mdl-37263758

ABSTRACT

OBJECTIVES: Most patients in palliative oncology care are polymorbid and thus treated with multiple drugs. The therapeutic effect and safety of these drugs can be compromised by drug/drug interactions, but also by wider problems such as polypharmacy and compliance. The clinical pharmacist is, therefore, responsible for risk analysis and prevention. Our prospective open label non-randomised clinical study evaluated the importance of a clinical pharmacist in the palliative care team. METHODS: A total of 250 outpatients were included in the clinical study: 126 women (50.4%) and 124 men (49.6%), with a mean age of 71 years (range 21-94 years; SD 11.9). The patients had the performance status scale 0-3 [Formula: see text]. Clinical examinations were performed on a monthly basis (n=509 check-up visits). The clinical pharmacist prepared an educational chart for all medications used after each visit and evaluated any drug-related problems. Follow-up was 6 months. RESULTS: This study found a significant association between drug related-problems and polypharmacy (p<0.001). A low risk of drug-rfelated problems was observed during the initial visit, that is, 68 female (27.2%) and 25 male (10.4%) patients. A greater clinical-pharmaceutical risk was observed among the patients taking antihypertensive drugs (p=0.003) and/or beta blockers (p=0.048). CONCLUSION: This study confirms the essential role of a clinical pharmacist in oncology palliative care. The feedback obtained from the patients showed a notable improvement in their quality of life. Further, this clinical study confirmed the need for a personalised approach in palliative oncology care.


Subject(s)
Palliative Medicine , Humans , Male , Female , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Prospective Studies , Pharmacists , Quality of Life , Medication Adherence , Pharmaceutical Preparations
11.
Vaccines (Basel) ; 12(3)2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38543933

ABSTRACT

Aside from the general population, the COVID-19 pandemic has also affected a group of patients in palliative oncology care. In this study, long-term immune responses against SARS-CoV-2 after vaccination were monitored in a cohort of patients in palliative oncology care. This non-randomized, prospective, and open-label pilot study recruited patients from the Palliative Oncology Program and included 147 patients, of which 80 were females (54.4%) and 67 males (45.6%). The overall evaluation included current health status, SARS-CoV-2 anti-S IgG titer, and neutralizing antibodies using the SARS-CoV-2 virus neutralization test (VNT). Anti-S IgG antibody analysis revealed high (H) antibody levels in 35.7% (n = 10) and very high (VH) levels in 39.3% (n = 11) of patients after the second vaccination dose. Similarly, after the third dose, H was found in 29.6% (n = 32) and VH in 55.5% (n = 60) of patients. High and very high anti-S IgG antibody levels were consistent with high VNT titers (>2560) and H antibody levels in 17.1% (n = 12) or VH in 82.9% (n = 58) of patients. Patients with two or more doses showed H and VH antibody levels at a median of 451 and 342 days after vaccination, respectively. In this clinical trial, patients showed high and very high levels of anti-S IgG antibodies over a longer period of time. These patients did not show reduced immunological responses to the COVID-19 vaccine challenge. We can assume that prevention through vaccination can reduce the risk of complications or death from COVID-19 in patients in early palliative oncology care.

12.
Acta Medica (Hradec Kralove) ; 56(1): 29-32, 2013.
Article in English | MEDLINE | ID: mdl-23909052

ABSTRACT

INTRODUCTION: Annually more than 27,000 persons die of cancer in the Czech Republic and the overall incidence of malignancies is still increasing. These data shows the need for affordable and good follow-up care especially for patients without any cancer treatment due to irreversible progression of tumor. Currently the outpatient palliative cancer care gets more into the forefront. Prerequisite for a well working outpatient palliative care is cooperation with general practitioners and home health care agencies. The purpose of the so called program of palliative cancer care is to guide a patient in palliative cancer care and to improve the cooperation among health care providers. METHODS: During the period from January 2008 to October 2010 we evaluated in patient without any oncology treatment due to irreversible progression of tumor. RESULTS: In palliative outpatient clinic we treated 446 patients, 119 of them received home care services with average length of 27.8 days. 77 patients died at home, 51 in health facilities and 41 in inpatient hospice care. CONCLUSION: We present pilot study focusing on outpatient palliative cancer care which shows the real benefit from early indication of palliative cancer care. This type of care allows patients to stay as long as possible at home among their close relatives.


Subject(s)
Home Care Services/organization & administration , Hospice Care/organization & administration , Neoplasms/therapy , Oncology Service, Hospital/organization & administration , Palliative Care/organization & administration , Adolescent , Adult , Aged , Aged, 80 and over , Czech Republic , Female , Humans , Male , Middle Aged , Neoplasms/mortality , Neoplasms/pathology , Young Adult
13.
J Med Food ; 26(12): 943-950, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37831915

ABSTRACT

Objective: The implementation of nutritional support is a basic need of patients in palliative oncological care. This pilot study optimized the use of sipping to improve the nutritional status of cancer patients in palliative care. Materials and Method: The pilot study included 63 patients, 61.3 years of age on average (range: 32-82 years of age). The patients were assigned to either group A (no nutritional support n = 39 patients) or group B (sipping as nutritional support n = 24 patients). The patients were evaluated through by noninvasive methods: body weight, waist and arm circumference, and triceps skinfold, bioimpedance analysis, and dynamometry. Quality of life was assessed through modified questionnaires. Results: In contrast with group A, group B did not have a significant weight loss, that is, A: 81.9 ± 15.8-80.5 ± 15.8 kg (P = .028) and B: 73.9 ± 14.9-73 ± 16 kg. Body mass index A: 29 ± 5-28.5 ± 5 kg/m2 (P = .007) and B: 25.3 ± 4.7-25 ± 4.9 kg/m2 (P = .614). Waist circumference A: 93.5 ± 15.1-92.5 ± 14.8 cm (P = .008) and B: 80.1 ± 13.2-80.6 ± 12.3 cm (P = .234). Triceps skinfold A: 12.3 ± 7.2-11 ± 6.7 mm (P = .001) and B: 8.2 ± 6.1-7.9 ± 5.7 mm (P = .207). Fat free mass A: 54.8 ± 11.5-52.8 ± 11.6 kg (P = .018) and B: 54.7 ± 10.9-52.8 ± 11.5 kg (P = .207). Significantly lower dynamometer values were recorded in both groups; A: 25.6 ± 10.4-23.1 ± 10.3 kg (P = .010) and B: 27.4 ± 9.9-24.3 ± 9.1 kg (P = .009). In contrast to group B, the patients in group A showed slight variations in their health status, thus decreasing their scores into the significance limit (P = .072). Conclusion: Our results suggest that providing nutritional support in the form of sipping (∼12 g proteins, 300 kcal) on a daily basis prevents the loss of active tissue mass in palliative oncology patients. Based on these results, we recommend the inclusion of this simple nutritional support to prevent malnutrition in cancer patients in palliative care. The clinical study was registered by the internal ethics committee under the heading of its approval - Institutional Ethics Committee of the Hradec Králové Faculty Hospital, number 201311S2OP.


Subject(s)
Neoplasms , Palliative Care , Humans , Adult , Middle Aged , Aged , Aged, 80 and over , Pilot Projects , Quality of Life , Nutritional Status , Neoplasms/therapy
14.
J Pers Med ; 13(5)2023 Apr 28.
Article in English | MEDLINE | ID: mdl-37240931

ABSTRACT

Modern communication and information technologies are rapidly being deployed at health care institutions around the world. Although these technologies offer many benefits, ensuring data protection is a major concern, and implementation of robust data protection measures is essential. In this context, health care providers and medical care facilities must frequently make difficult decisions and compromises between the need to provide effective medical care and the need to ensure data security and patient privacy. In the present paper, we describe and discuss key issues related to data protection systems in the setting of cancer care hospitals in Europe. We provide real-life examples from two European countries-Poland and the Czech Republic-to illustrate data protection issues and the steps being taking to address these questions. More specifically, we discuss the legal framework surrounding data protection and technical aspects related to patient authentication and communication.

15.
Front Oncol ; 13: 1133598, 2023.
Article in English | MEDLINE | ID: mdl-37182133

ABSTRACT

Despite distant metastases being the critical factor affecting patients' survival, they remain poorly understood. Our study thus aimed to molecularly characterize colorectal cancer liver metastases (CRCLMs) and explore whether molecular profiles differ between Synchronous (SmCRC) and Metachronous (MmCRC) colorectal cancer. This characterization was performed by whole exome sequencing, whole transcriptome, whole methylome, and miRNAome. The most frequent somatic mutations were in APC, SYNE1, TP53, and TTN genes. Among the differently methylated and expressed genes were those involved in cell adhesion, extracellular matrix organization and degradation, neuroactive ligand-receptor interaction. The top up-regulated microRNAs were hsa-miR-135b-3p and -5p, and the hsa-miR-200-family while the hsa-miR-548-family belonged to the top down-regulated. MmCRC patients evinced higher tumor mutational burden, a wider median of duplications and deletions, and a heterogeneous mutational signature than SmCRC. Regarding chronicity, a significant down-regulation of SMOC2 and PPP1R9A genes in SmCRC compared to MmCRC was observed. Two miRNAs were deregulated between SmCRC and MmCRC, hsa-miR-625-3p and has-miR-1269-3p. The combined data identified the IPO5 gene. Regardless of miRNA expression levels, the combined analysis resulted in 107 deregulated genes related to relaxin, estrogen, PI3K-Akt, WNT signaling pathways, and intracellular second messenger signaling. The intersection between our and validation sets confirmed the validity of our results. We have identified genes and pathways that may be considered as actionable targets in CRCLMs. Our data also provide a valuable resource for understanding molecular distinctions between SmCRC and MmCRC. They have the potential to enhance the diagnosis, prognostication, and management of CRCLMs by a molecularly targeted approach.

16.
Radiat Environ Biophys ; 51(2): 205-13, 2012 May.
Article in English | MEDLINE | ID: mdl-22278290

ABSTRACT

In the work presented here, changes in haematopoiesis of mice (B6129SF2/J) were studied 1 year after their whole-body exposure to a dose of 7 Gy (72% of mice survived). The irradiated mice were compared with non-irradiated younger (4 months of age) and older (16 months of age) mice. There was a significant increase in the relative abundance of primitive stem cells with long-term capability of the haematopoiesis recovery lin(-)/Sca-1(+)/CD117(+)/CD34(-) in the bone marrow of mice aged 16 months (irradiated and non-irradiated) compared with those aged 4 months. In terms of the ability to respond to further whole-body irradiation at a dose of 1 Gy, the presence of γH2A.X foci was studied in lin(-) bone marrow cells. There was a considerable number of persisting foci in lin(-) stem cells isolated from the bone marrow of the older irradiated mice. In the blood count from the peripheral blood of the older mice (both non-irradiated and irradiated at 7 Gy), there was a significant increase in granulocytes. In the group exposed to 7 Gy, the numbers of thrombocytes significantly increased, and on the contrary, the numbers of erythrocytes, the amount of haemoglobin, and haematocrit significantly decreased.


Subject(s)
Hematopoiesis/radiation effects , Hematopoietic Stem Cells/radiation effects , Age Factors , Animals , Blood Platelets/metabolism , Blood Platelets/radiation effects , Bone Marrow/radiation effects , Cell Line , Erythrocytes/metabolism , Erythrocytes/radiation effects , Female , Granulocytes/metabolism , Granulocytes/radiation effects , Hematopoietic Stem Cells/cytology , Hematopoietic Stem Cells/metabolism , Hemoglobins/metabolism , Hemoglobins/radiation effects , Histones/metabolism , Male , Mice , Whole-Body Irradiation/methods
17.
Acta Medica (Hradec Kralove) ; 55(4): 153-9, 2012.
Article in English | MEDLINE | ID: mdl-23631285

ABSTRACT

The colorectal cancer ranks high among the malignant tumours in incidence and mortality and irinotecan is standardly used in palliative treatment of metastatic disease in every therapeutic line. Unfortunately, the treatment with irinotecan is often associated with severe toxicities, especially neutropenia and diarrhea. The majority of the toxic manifestation is caused by the insufficient deactivation (glucuronidation) of irinotecan active metabolite SN-38 by UGT1A enzyme. The elevated SN-38 plasma concentration is responsible for the hematological and gastrointestinal toxicity that can become life-threatening. The patients carrying the mutation of the gene encoding UGT1A enzyme lack the ability of bilirubin glucuronidation, and suffer from the inherited un-conjugated hyperbilirubinemia (Gilbert syndrome, Crigler-Najjar type 1 and 2 syndrome). The mutations in other enzyme systems also play role in the etiopathogenesis of the irinotecan toxicity: CYP3A (cytochrome P-450), ABC family of transmembrane transporters (adenosine-triphosphate binding cassette). The goal of the contemporary research is to determine the predictive factors that will enable the individual adjustment of the individual drug dosage while minimising the adverse effects and maintaining the treatment benefit.


Subject(s)
Antineoplastic Agents, Phytogenic/adverse effects , Camptothecin/analogs & derivatives , Colorectal Neoplasms/pathology , Antineoplastic Agents, Phytogenic/pharmacokinetics , Antineoplastic Agents, Phytogenic/therapeutic use , Camptothecin/adverse effects , Camptothecin/pharmacokinetics , Camptothecin/therapeutic use , Colorectal Neoplasms/genetics , Diarrhea/chemically induced , Humans , Irinotecan , Neutropenia/chemically induced , Pharmacogenetics
18.
Biomedicines ; 10(11)2022 Nov 14.
Article in English | MEDLINE | ID: mdl-36428486

ABSTRACT

Background. The treatment of middle ear cholesteatoma requires surgical treatment and the reconstruction of the temporal bone, which represents an ongoing problem. Otologists have focused on the research of materials allowing an airy middle ear and the preservation of hearing function to reconstruct the temporal bone. Methods. This study evaluated the effect of cyclosporin A (CsA) and a combined biomaterial in the healing process of postoperative temporal bone defects in an animal model. Cultured human Bone Marrow Mesenchymal Stromal Cells (hBM-MSCs) were mixed with hydroxyapatite (Cem-Ostetic®), and subsequently applied as a bone substitute after middle ear surgery, showing that the therapeutic potential of hBM-MSCs associated with bone regeneration and replacement is directly influenced by CsA, confirming that it promotes the survival of MSCs in vivo. Results. The therapeutic efficacy of the combination of MSCs with CsA is greater than the sole application of MSCs in a hydroxyapatite carrier. Conclusion. The reconstruction of a temporal bone defect using hBM-MSCs requires an immunosuppressant to improve the results of treatment.

19.
Transfus Apher Sci ; 45(3): 251-6, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22018894

ABSTRACT

We describe our experience with plasma exchange (PE) and immunoadsorption in patients with myasthenia gravis. The group of 27 patients consists of 21 patients treated with PE and 6 patients who received immunoadsorption. PE therapy led to stabilization in 20 patients. In patients treated with immunoadsorption, therapy could be discontinued in 2 patients after 13 months of therapy, and the other 4 patients were stabilized without myasthenic crises after 6-9 years of therapy. Extracorporeal elimination therapy through PE or immunoadsorption is effective and sometimes life saving and is safe in the hands of an experienced team (6% complication rate).


Subject(s)
Hemofiltration/methods , Myasthenia Gravis/therapy , Plasma Exchange/methods , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Time Factors
20.
Cas Lek Cesk ; 150(3): 169-72, 2011.
Article in Czech | MEDLINE | ID: mdl-21560456

ABSTRACT

Palliative treatment and related nursing care are currently a major problem in the organization of health care. Outpatient palliative cancer care (OPCC) helps to verify the clinical status of cancer patients and helps to choose the best treatment options and their completion. The OPCC has to be able to provide all treatment possibilities of cancer related symptoms such as cancer pain or symptoms related with cancer therapy. During tracking period in the OPCC, 446 patients were treated--288 women, mean age 61 years (age range 20-81 years) and 158 men, mean age 56 years (age range 18-96 years). According to the assessment of performance status (PS) there was following stratification: PS-0 (8%), PS-1 (54%), PS-2 (33%) and PS-3 (5%). The OPCC uses a uniform system of medical records, uniform system for assessing the quality and quantity of health care--and determination of "minimal health care". Here we present our results, which reflect the need of cooperation of all, who are involved in health care of cancer patient--collaboration between the general practitioner (GP), oncology departments, including hospice and home care agencies.


Subject(s)
Home Care Services , Neoplasms/therapy , Palliative Care , Adult , Aged , Female , Humans , Male , Middle Aged , Palliative Care/organization & administration , Young Adult
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