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1.
BMC Cancer ; 24(1): 142, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38287290

RESUMO

BACKGROUND: The prognostic significance of mast cells and different phenotypes of macrophages in the microenvironment of hepatocellular carcinoma (HCC) following resection is unclear. We aimed in this study to assess the local distribution of infiltrating macrophages and mast cells of specific phenotypes in tissues of HCC and to evaluate their prognostic values for survival of post-surgical patients. METHODS: The clinicopathological and follow-up data of 70 patients with HCC, who underwent curative resection of tumor from 1997 to 2019, were collected. The infiltration of CD68+ and CD163+ macrophages and CD117+ mast cells was assessed immunohistochemically in representative resected specimens of HCC and adjacent tissues. The area fraction (AF) of positively stained cells was estimated automatically using QuPath image analysis software in several regions, such as tumor center (TC), inner margin (IM), outer margin (OM), and peritumor (PT) area. The prognostic significance of immune cells, individually and in associations, for time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS) was evaluated using Kaplan-Meier and Cox regression analyses. RESULTS: High AF of CD68+ macrophages in TC and IM and high AF of mast cells in IM and PT area were associated with a longer DFS. High AF of CD163+ macrophages in PT area correlated with a shorter DFS. Patients from CD163TChigh & CD68TClow group had a shorter DFS compared to all the rest of the groups, and cases with CD163IMlow & CD68IMhigh demonstrated significantly longer DFS compared to low AF of both markers. Patients from CD68IMhigh & CD163PTlow group, CD117IMhigh & CD163PTlow group, and CD117PThigh & CD163PTlow group had a significantly longer DFS compared to all other combinations of respective cells. CONCLUSIONS: The individual prognostic impact of CD68+ and CD163+ macrophages and mast cells in the microenvironment of HCC after resection depends on their abundance and location, whereas the cumulative impact is built upon combination of different cell phenotypes within and between regions.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Prognóstico , Neoplasias Hepáticas/patologia , Mastócitos/patologia , Estimativa de Kaplan-Meier , Macrófagos/patologia , Microambiente Tumoral
2.
Cancer Med ; 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38164124

RESUMO

BACKGROUND: The introduction of novel hormonal therapies represented by enzalutamide (ENZ) and abiraterone acetate (ABI) has reached a great progress in the treatment of metastatic castration-resistant prostate cancer (mCRPC). The majority of mCRPC patients are elderly suffering from chronic co-morbidities requiring use of various concomitant medications. In the present study, we focused on impact of concomitant antihypertensive medication on the outcomes of mCRPC patients treated with ENZ or ABI. METHODS: In total, 300 patients were included and their clinical data were retrospectively analyzed. RESULTS: Angiotensin-converting enzyme inhibitors (ACEIs) represented the only concomitant medication significantly associated with survival. The median radiographic progression-free survival (rPFS) and overall survival (OS) for patients using ACEIs were 15.5 and 32.3 months compared to 10.7 and 24.0 months for those not using ACEIs (p = 0.0053 and p = 0.0238, respectively). Cox multivariable analysis revealed the use of ACEIs a significant predictive factor for both rPFS (HR = 0.704, p = 0.0364) and OS (HR = 0.592, p = 0.0185). CONCLUSION: The findings of this study suggest an association between the concomitant use of ACEIs and longer survival of mCRPC patients receiving ENZ or ABI therapy.

3.
In Vivo ; 37(5): 2229-2236, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37652490

RESUMO

BACKGROUND/AIM: The aim of this study was to investigate possible association between adverse events of nivolumab therapy and the effectiveness of treatment in patients with non-small cell lung cancer (NSCLC). Focusing on serious adverse events (i.e., those of grade ≥3), we evaluated overall survival (OS), progression-free survival (PFS), as well as objective response rate (ORR) to treatment. PATIENTS AND METHODS: We retrospectively analyzed a set of patients from the TULUNG database of NSCLC treated with nivolumab in eight oncology centers. We evaluated OS data based upon this set. To reduce possible bias, we further evaluated a subgroup of patients treated at the University Hospital in Pilsen, where the occurrence of adverse events, PFS, and ORR were independently examined by two experienced physicians. Survival statistics were evaluated using the Kaplan-Meier method and Cox analysis. RESULTS: We observed significantly greater OS, PFS, and ORR in the group of patients experiencing adverse events upon nivolumab treatment versus in those patients without such events. Although the univariable model analyzing the data set of all patients demonstrated higher OS in patients with serious adverse events, only a nonsignificant trend was observed in the Cox multivariable model. In a subgroup of patients with PFS and ORR evaluation, we did observe significant, favorable effects for patients having had serious adverse effects. CONCLUSION: Patients experiencing severe adverse events show a tendency toward better OS, PFS, and ORR compared to patients without or having only mild adverse events with nivolumab treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Nivolumabe/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/epidemiologia , Estudos Retrospectivos , Intervalo Livre de Progressão
4.
Sci Rep ; 13(1): 9097, 2023 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-37277368

RESUMO

Telomeric sequences, the structures comprised of hexanucleotide repeats and associated proteins, play a pivotal role in chromosome end protection and preservation of genomic stability. Herein we address telomere length (TL) dynamics in primary colorectal cancer (CRC) tumour tissues and corresponding liver metastases. TL was measured by multiplex monochrome real-time qPCR in paired samples of primary tumours and liver metastases along with non-cancerous reference tissues obtained from 51 patients diagnosed with metastatic CRC. Telomere shortening was observed in the majority of primary tumour tissues compared to non-cancerous mucosa (84.1%, p < 0.0001). Tumours located within the proximal colon had shorter TL than those in the rectum (p < 0.05). TL in liver metastases was not significantly different from that in primary tumours (p = 0.41). TL in metastatic tissue was shorter in the patients diagnosed with metachronous liver metastases than in those diagnosed with synchronous liver metastases (p = 0.03). The metastatic liver lesions size correlated with the TL in metastases (p < 0.05). Following the neoadjuvant treatment, the patients with rectal cancer had shortened telomeres in tumour tissue than prior to the therapy (p = 0.01). Patients with a TL ratio between tumour tissue and the adjacent non-cancerous mucosa of ≥ 0.387 were associated with increased overall survival (p = 0.01). This study provides insights into TL dynamics during progression of the disease. The results show TL differences in metastatic lesions and may help in clinical practice to predict the patient's prognosis.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Hepáticas , Neoplasias Retais , Humanos , Prognóstico , Telômero/genética , Telômero/patologia , Neoplasias Colorretais/patologia , Encurtamento do Telômero
5.
J Cancer ; 14(1): 1-8, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36605490

RESUMO

Purpose: To investigate potential association between selected tumor markers and laboratory parameters (lactate dehydrogenase [LDH], neutrophils, hemoglobin, neutrophils, lymphocytes, C-reactive protein, albumin, carcinoembryonic antigen, and cytokeratin 19 fragment 21-1 [CYFRA 21-1]) and circulating tumor DNA (ctDNA) with survival in patients with advanced non-small cell lung cancer (NSCLC). Patients and Methods: The study encompassed 82 patients from a single center. All patients had (localy-) advanced adenocarcinomas. ctDNA was determined before starting therapy and at 6 weeks follow-up. Laboratory parameters were measured before each cycle of therapy and oncomarkers before starting the therapy as standard clinical practice. Mann-Whitney U test, Cox proportional hazards model, Fisher's exact test, and Kaplan-Meier survival estimation with Gehan-Wilcoxon test were used for statistical analysis of the corresponding variables. Results: We have confirmed predictive or prognostic significance for some of the selected laboratory markers and oncomarkers. Above all, we demonstrate a significant relationship between the levels of LDH and the oncomarker CYFRA 21-1 and the presence or absence of ctDNA at the time of diagnosis. We also demonstrate significantly lower CRP levels in patients within whom the ctDNA disappeared during treatment. A similar but statistically insignificant trend was observed for LDH. Conclusions: CYFRA 21-1, LDH and probably CRP correlate with ctDNA levels in NSCLC. Repeated measurement of these markers could thus help in early detection of disease progression in the same way as does ctDNA monitoring.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34897298

RESUMO

OBJECTIVE: The aim of the study was to investigate the associations of cross-sectional area (CSA) of the median nerve measured by ultrasonography, the median to ulnar nerve ratio (MUR), the median to ulnar nerve difference (MUD) and the ratio of CSA of the median nerve to height squared (MHS) in relation to electrodiagnostic classification of moderate and severe carpal tunnel syndrome (CTS) and thus to identify patients suitable for surgical treatment. MATERIALS AND METHODS: A prospective study was conducted in patients aged ≥ 18 years who underwent both median and ulnar nerve ultrasonography and electrodiagnostic studies (EDS). 124 wrists of 62 patients were examined. The patients' characteristics were acquired through a questionnaire. CTS was diagnosed using EDS and classified according to the guidelines of the Czech Republic Association of Electrodiagnostic Medicine. The CSA of the median nerve and of the ulnar nerve were measured at the carpal tunnel inlet. RESULTS: Median nerve CSA at the tunnel inlet ≥ 12 mm2 correlates with electrodiagnostic classification of moderate to severe carpal tunnel syndrome. At this cut-off value, the sensitivity of ultrasonography is 82.4%, its specificity is 87.7%, the positive predictive value is 82.4%, the negative predictive value is 87.7%. MUD, MUR and MHS perform worse than the median nerve CSA, as shown by their lower area under the receiver operating characteristic curve. CONCLUSIONS: Ultrasound could help us indicate surgical treatment for CTS, especially in patients with clinical findings. Our results suggest a cut-off value of CSA at the tunnel inlet of ≥ 12mm2.


Assuntos
Síndrome do Túnel Carpal , Nervo Mediano , Humanos , Nervo Mediano/diagnóstico por imagem , Síndrome do Túnel Carpal/diagnóstico por imagem , Estudos Prospectivos , Curva ROC , Ultrassonografia/métodos , Sensibilidade e Especificidade
7.
Theriogenology ; 195: 115-121, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36332370

RESUMO

Bulls used in artificial insemination programmes worldwide undergo quality control checks, which are typically based on the evaluation of sperm motility and morphology. Despite this, some bulls can have lower than expected field fertility and the reasons for this remain to be elucidated. Here we hypothesised that sperm from bulls of varying fertility will differ in their ability to undergo capacitation-related events including an increase in membrane fluidity, protein tyrosine phosphorylation, hyperactivation and the acrosome reaction. Firstly, we used frozen-thawed semen from 10 high-fertility (HF) and 10 low-fertility (LF) bulls, and subjected them to in vitro capacitating conditions, following which sperm viability, membrane fluidity, acrosome integrity and protein tyrosine phosphorylation were assessed using flow cytometry. We then assessed the ability of sperm to undergo hyperactivation (induced using caffeine) utilising computer-assisted sperm analysis, and the acrosome reaction (induced using calcium ionophore) using flow cytometry. When sperm were incubated in capacitating conditions, a higher percentage of viable sperm from HF bulls exhibited high membrane fluidity when compared to LF bulls (8.8 ± 0.8% and 5.8 ± 1.2%, respectively; mean ± standard error; P < 0.05). There was no difference between fertility groups in the percentage of acrosome-reacted sperm following the incubation in in vitro capacitating conditions or following the induction of the acrosome reaction using calcium ionophore. However, more sperm from HF bulls became hyperactive in response to caffeine stimulation than sperm from LF bulls (21.6 ± 2.5% versus 14.1 ± 2.4%, respectively; mean ± standard error; P < 0.05). Taken together, sperm from LF bulls had an impaired ability to undergo membrane remodulation and to hyperactivate when induced in vitro. These are key events in the journey of sperm along the female reproductive tract and in the interaction with the oocyte and thus could explain the lower field fertility exhibited by some bulls.


Assuntos
Cafeína , Sêmen , Masculino , Feminino , Bovinos , Animais , Ionóforos de Cálcio , Motilidade dos Espermatozoides , Espermatozoides , Tirosina
8.
Anticancer Res ; 43(1): 463-471, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36585174

RESUMO

BACKGROUND/AIM: Enzalutamide (ENZ) and abiraterone acetate with prednisone (AAP) represent novel hormonal therapies used in the treatment of metastatic castration-resistant prostate cancer (mCRPC). The aim of the study was to assess the long-term outcome of mCRPC patients treated with ENZ or AAP in real-life clinical practice. PATIENTS AND METHODS: The outcomes of 337 mCRPC patients treated with ENZ or AAP were retrospectively analysed. RESULTS: Median radiographic progression-free (rPFS) and overall survival (OS) of patients treated in the first line (pre-chemotherapy) was 13.89 (95% CI=12.40-16.80) and 31.02 (95% CI=24.27-37.44) months vs. 10.97 (95% CI=8.97-14.82) and 26.57 (95% CI=15.97-33.92) months for those treated in the second line (post-chemotherapy). We found inferior survival for patients with synchronous metastases, high Gleason score (GS) and visceral metastases. CONCLUSION: The efficacy of both ENZ and AAP in mCRPC patients is herein confirmed. Synchronous metastases, high GS and visceral metastases were identified as significant adverse prognostic factors.


Assuntos
Acetato de Abiraterona , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Acetato de Abiraterona/uso terapêutico , Prednisona/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos , Nitrilas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resultado do Tratamento
9.
Rep Pract Oncol Radiother ; 28(6): 746-755, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38515821

RESUMO

Background/Objective: Hormone receptor (HR) status is one of the key factors in determining the treatment of breast cancer. Previous studies suggested that HR status may change in metastatic tissue. However, available studies focused mainly on primary biopsies and there are only few trials comparing HR status in the primary tumour and the metastasis using material from complete resection. The aim of the study was to determine the frequency of HR alterations in metastatic breast cancer. Materials and methods: The study retrospectively examines a total of 50 patients who underwent brain, lung, or liver metastasectomy for metastatic breast cancer between January 2000 and January 2019. Results: HR conversion was observed in a total of 30 cases (60.0%), while HER-2/neu (human epidermal growth factor receptor 2) discrepancy surprisingly occurred only in one case (2.0%). A change in immunophenotype occurred in 28% of cases. Triple-negativity was more frequent in brain metastases (p = 0.039). Conclusions: We have confirmed that HR conversion between the primary tumour and its metastases occurs in a significant number of cases, which has important implications for further treatment decisions.

10.
Front Oncol ; 12: 962929, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36203452

RESUMO

We investigated the possible associations between leukocyte telomere length, therapy outcomes, and clinicopathological features in patients with colorectal cancer. Additionally, telomerase reverse transcriptase (TERT) expression was evaluated. Telomere length was measured using singleplex qPCR in 478 consecutive leukocyte DNA samples from 198 patients. Blood was drawn at diagnosis prior to any therapy and then at 6-month intervals for 18 months. Following diagnosis, the telomeres gradually shortened during the course of the treatment regardless of the patient's age. The most pronounced decrease was observed 12 months after the diagnosis (p < 0.0001). Based on tumor localization, the decrease in telomere length one year after the diagnosis followed different trajectories (p = 0.03). In patients treated with adjuvant therapy, telomere length correlated with the time elapsed after completion of therapy (p = 0.03). TERT expression did not correlate with the telomere length; however, it was higher in women than men (1.35-fold, 95% CI 1.11-1.65, p = 0.003) and in smokers than non-smokers (1.27-fold, 95% CI 1.01-1.61, p = 0.04). Leukocyte telomere length declines naturally during aging, but the accelerated shortening observed in our patients was age-independent. Telomere length manifestly reflected chemotherapy impact and could be linked to therapy toxicity.

12.
Sci Rep ; 12(1): 11426, 2022 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-35794129

RESUMO

Persulfidation contributes to a group of redox post-translational modifications (PTMs), which arise exclusively on the sulfhydryl group of cysteine as a result of hydrogen sulfide (H2S) action. Redox-active molecules, including H2S, contribute to sperm development; therefore, redox PTMs represent an extremely important signalling pathway in sperm life. In this path, persulfidation prevents protein damage caused by irreversible cysteine hyperoxidation and thus maintains this signalling pathway. In our study, we detected both H2S and its production by all H2S-releasing enzymes (cystathionine γ-lyase (CTH), cystathionine ß-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (MPST)) in male reproduction, including spermatozoa. We provided evidence that sperm H2S leads to persulfidation of proteins, such as glyceraldehyde-3-phosphate dehydrogenase, tubulin, and anchor protein A-kinase. Overall, this study suggests that persulfidation, as a part of the redox signalling pathway, is tightly regulated by enzymatic H2S production and is required for sperm viability.


Assuntos
Sulfeto de Hidrogênio , Cistationina gama-Liase/metabolismo , Cisteína/metabolismo , Humanos , Sulfeto de Hidrogênio/metabolismo , Masculino , Reprodução , Sêmen/metabolismo
13.
BMC Genomics ; 23(1): 379, 2022 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-35585482

RESUMO

BACKGROUND: Despite a multifactorial approach being taken for the evaluation of bull semen quality in many animal breeding centres worldwide, reliable prediction of bull fertility is still a challenge. Recently, attention has turned to molecular mechanisms, which could uncover potential biomarkers of fertility. One of these mechanisms is DNA methylation, which together with other epigenetic mechanisms is essential for the fertilising sperm to drive normal embryo development and establish a viable pregnancy. In this study, we hypothesised that bull sperm DNA methylation patterns are related to bull fertility. We therefore investigated DNA methylation patterns from bulls used in artificial insemination with contrasting fertility scores. RESULTS: The DNA methylation patterns were obtained by reduced representative bisulphite sequencing from 10 high-fertility bulls and 10 low-fertility bulls, having average fertility scores of - 6.6 and + 6.5%, respectively (mean of the population was zero). Hierarchical clustering analysis did not distinguish bulls based on fertility but did highlight individual differences. Despite this, using stringent criteria (DNA methylation difference ≥ 35% and a q-value < 0.001), we identified 661 differently methylated cytosines (DMCs). DMCs were preferentially located in intergenic regions, introns, gene downstream regions, repetitive elements, open sea, shores and shelves of CpG islands. We also identified 10 differently methylated regions, covered by 7 unique genes (SFRP1, STXBP4, BCR, PSMG4, ARSG, ATP11A, RXRA), which are involved in spermatogenesis and early embryonic development. CONCLUSION: This study demonstrated that at specific CpG sites, sperm DNA methylation status is related to bull fertility, and identified seven differently methylated genes in sperm of subfertile bulls that may lead to altered gene expression and potentially influence embryo development.


Assuntos
Metilação de DNA , Análise do Sêmen , Animais , Bovinos , Desenvolvimento Embrionário/genética , Feminino , Fertilidade/genética , Masculino , Gravidez , Espermatozoides/metabolismo
15.
Sci Rep ; 12(1): 2570, 2022 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-35173208

RESUMO

A large proportion of colorectal carcinomas (CRC) evolve from colorectal adenomas. However, not all individuals with colonic adenomas have a risk of CRC substantially higher than those of the general population. The aim of the study was to determine the differences or similarities of mutation profile among low- and high-grade adenomas and in situ carcinoma with detailed follow up. We have investigated the mutation spectrum of well-known genes involved in CRC (such as APC, BRAF, EGFR, NRAS, KRAS, PIK3CA, POLE, POLD1, SMAD4, PTEN, and TP53) in a large, well-defined series of 96 adenomas and in situ carcinomas using a high-throughput genotyping technique. Besides, the microsatellite instability and APC and MLH1 promoter methylation were studied as well. We observed a high frequency of pathogenic variants in the studied genes. The APC, KRAS and TP53 mutation frequencies were slightly lower in adenoma samples than in in situ carcinoma samples. Further, when we stratified mutation frequency based on the grade, the frequency distribution was as follows: low-grade adenoma-high-grade adenomas-in situ carcinoma: APC gene 42.9-56.0-54.5%; KRAS gene 32.7-32.0-45.5%; TP53 gene 8.2-20.0-18.2%. The occurrence of KRAS mutation was associated with the presence of villous histology and methylation of the APC promoter was significantly associated with the presence of POLE genetic variations. However, no association was noticed with the presence of any singular mutation and occurrence of subsequent adenoma or CRC. Our data supports the multistep model of gradual accumulation of mutations, especially in the driver genes, such as APC, TP53 and KRAS.


Assuntos
Adenoma/patologia , Biomarcadores Tumorais/genética , Carcinoma in Situ/patologia , Neoplasias Colorretais/patologia , Instabilidade de Microssatélites , Mutação , Adenoma/genética , Idoso , Carcinoma in Situ/genética , Neoplasias Colorretais/genética , Metilação de DNA , Feminino , Seguimentos , Humanos , Masculino , Prognóstico
16.
Cancer Genomics Proteomics ; 19(2): 270-281, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35181593

RESUMO

BACKGROUND/AIM: Circulating tumour DNA (ctDNA) represents an emerging biomarker in non-small cell lung cancer (NSCLC). We focused on the combination of ctDNA and positron emission tomography/computed tomography (PET/CT) in the follow-up monitoring of advanced-stage NSCLC patients treated with chemotherapy. PATIENTS AND METHODS: Eighty-four patients were enrolled in this study. 18F-fluorodeoxyglucose PET/CT and ctDNA assessments were performed at baseline and after two cycles of chemotherapy (follow-up). RESULTS: There was a correlation of ctDNA with metabolic tumour volume (MTV), total lesion glycolysis (TLG), and iodine concentration (IC) at baseline (p=0.001, p=0.001, p=0.003) and at follow-up (p=0.006, p=0.002, p=0.001). The objective response was associated with follow-up ctDNA (p<0.001) and the change of all PET/CT parameters. ROC analyses showed that the combination of follow-up ctDNA with changes in SUVmax is very promising for the estimation of objective response and progression-free survival. CONCLUSION: The combination of ctDNA assessment with PET/CT is a promising approach for the follow-up monitoring of therapy response and prognosis estimation of advanced-stage NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , DNA Tumoral Circulante , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , DNA Tumoral Circulante/genética , Fluordesoxiglucose F18/metabolismo , Fluordesoxiglucose F18/uso terapêutico , Glicólise , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Prognóstico , Estudos Prospectivos , Compostos Radiofarmacêuticos/uso terapêutico , Estudos Retrospectivos , Carga Tumoral
17.
Cancers (Basel) ; 14(3)2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35158872

RESUMO

In this retrospective study on 67 patients with hepatocellular carcinoma (HCC), after tumor resection, we evaluated the significance of CD3+ and CD8+ T-lymphocytes and CD20+ B-lymphocytes in tumor and non-tumor liver for time to recurrence (TTR), disease-free survival (DFS) and overall survival. After immunohistochemical staining, the density of nucleated lymphocyte profiles (QA) was estimated stereologically in the tumor center (TC), inner margin (inn M), outer margin (out M), peritumor and non-tumor liver. In TC, intermediate and high QA of CD8+ cells predicted longer TTR, whereas CD3+ and CD20+ were predictive only at high QA. DFS was predicted by high QA of CD3+, CD8+ and CD20+ cells in TC. The inn M harbored smaller QA of CD3+, CD8+ and CD20+ lymphocytes than out M. In contrast to out M, high T-cells' QA and intermediate and high B-cell QA in inn M predicted longer TTR and DFS. High inn M/out M QA ratios of CD3+ and CD20+ cells were associated with longer TTR and DFS, whereas high inn M/out M QA ratio of CD8+ was predictive only for DFS. Patients with intermediate-high QA of combined CD8+ and CD20+ cells in inn M showed longer TTR and DFS, compared to CD8+-high or CD20+-high alone. Our findings highlight overall heterogeneity of the tumor invasive margin, the importance of inn M, and the predictive role of B-cells.

18.
Cancers (Basel) ; 14(3)2022 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-35158910

RESUMO

The liquid biopsy has the potential to improve current clinical practice in oncology by providing real-time personalized information about a patient's disease status and response to treatment. In this study, we evaluated 161 peripheral blood (PB) samples that were collected around surgical resection from 47 metastatic colorectal cancer (mCRC) patients using the High-Definition Single Cell Assay (HDSCA) workflow. In conjunction with the standard circulating tumor cell (CTC) enumeration, cellular morphology and kinetics between time-points of collection were considered in the survival analysis. CTCs, CTC-Apoptotic, and CTC clusters were found to indicate poor survival with an increase in cell count from pre-resection to post-resection. This study demonstrates that CTC subcategorization based on morphological differences leads to nuanced results between the subtypes, emphasizing the heterogeneity within the CTC classification. Furthermore, we show that factoring in the time-point of each blood collection is critical, both for its static enumeration and for the change in cell populations between draws. By integrating morphology and time-based analysis alongside standard CTC enumeration, liquid biopsy platforms can provide greater insight into the pathophysiology of mCRC by highlighting the complexity of the disease across a patient's treatment.

19.
Strahlenther Onkol ; 198(9): 783-791, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35059759

RESUMO

PURPOSE: Image-guided adaptive brachytherapy (IGABT) is currently state of the art in the comprehensive treatment of patients with cervical cancer. Here, we report mature clinical data regarding IGABT of cervical cancer in a large patient sample, examining clinical outcomes, manifestations of late toxicities, and dosimetric findings. METHODS: Between May 2012 and October 2020, we performed a total of 544 uterovaginal IGABT applications in 131 consecutive patients with biopsy-proven cervical carcinoma not suitable for surgery. The median duration of follow-up was 43 months. RESULTS: The estimated 3­, 4­, and 5­year LC rates were 88.3% (95% confidence interval [CI] 81.1-95.5), 86.9% (95% CI 78.5-95.3), and 85.5% (95% CI 76-95%), respectively. The 3­, 4­, and 5­year OS estimates were 72.66% (95% CI 63.64-81.69%), 68.9% (95% CI 59.15-78.66%), and 63.96% (95% CI 52.94-74.97%), respectively. Patients who received ≥ 5 cycles of chemotherapy had statistically significantly better 3­year recurrence-free survival (RFS) compared to patients who completed <5 cycles (79.07% [95% CI 60.81-97.34] vs. 58.10% [95% CI 47.22-68.98]; p = 0.0185). We recorded manifestations of genitourinary and gastrointestinal toxicity grade ≥3 in 6.9% and 5.3%, respectively. CONCLUSION: Our mature long-term data on the treatment patients with locally advanced cervical cancer show that excellent treatment outcomes can be achieved with MRI-based IGABT, as well as acceptable late morbidity.


Assuntos
Braquiterapia , Radioterapia Guiada por Imagem , Neoplasias do Colo do Útero , Braquiterapia/efeitos adversos , Quimiorradioterapia/efeitos adversos , Feminino , Humanos , Imageamento por Ressonância Magnética , Estadiamento de Neoplasias , Dosagem Radioterapêutica , Radioterapia Guiada por Imagem/efeitos adversos , Resultado do Tratamento , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/radioterapia
20.
Artigo em Inglês | MEDLINE | ID: mdl-33542538

RESUMO

OBJECTIVES: The first objective of our study was to determine the radiation exposure received by patients during tin-filtrated ultra-low-dose computed tomography (TFULDCT) of sacroiliac joints and to compare those to conventional X-ray doses. For comparison, we added a cohort examined by low-dose CT (LDCT) without tin filtration. The second objective was to compare the results of TFULDCT and X-ray in the detection of sacroiliitis. METHODS: Our retrospective study covered 45 patients, who were examined for suspected axial spondyloarthritis (AxSpA). The first group underwent TFULDCT as well as conventional radiography (CR); the second group underwent LDCT only without tin filtration. Effective doses of TFULDCT, LDCT and CR were calculated by an experienced medical physicist. TFULDCT and CR were independently evaluated by three investigators, who decided on the presence or absence of rheumatoid inflammatory bone changes. The results were statistically evaluated. RESULTS: In our cohort, the median effective dose for TFULDCT was 0.11 mSv, range (0.06-0.40 mSv), for LDCT 0.5 mSv (0.29-0.89 mSv), and for CR 0.25 mSv (0.06-1.87 mSv). We proved that TFULDCT produces a significantly lower percentage of uncertain results (23.3%; 95% CI: 11.3-41.6%) than CR (66.7%; 95% CI: 48.3-81.1%). CONCLUSIONS: Tin filtration helps to reduce CT radiation exposure to values lower than those resulting from CR. TFULDCT offers better overall diagnostic performance than CR. Our results prove that TFULDCT can replace CR in the diagnosis of sacroiliitis in the radiographical stage of AxSpA.


Assuntos
Sacroileíte , Estanho , Humanos , Doses de Radiação , Radiografia , Estudos Retrospectivos , Sacroileíte/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Raios X
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