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1.
EBioMedicine ; 105: 105178, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38889481

RESUMEN

BACKGROUND: The accuracy of blood-based early tumour recognition is compromised by signal production at non-tumoral sites, low amount of signal produced by small tumours, and variable tumour production. Here we examined whether tumour-specific enhancement of vascular permeability by the particular tumour homing peptide, iRGD, which carries dual function of binding to integrin receptors overexpressed in the tumour vasculature and is known to promote extravasation via neuropilin-1 receptor upon site-specific cleavage, might be useful to improve blood-based tumour detection by inducing a yet unrecognised vice versa tumour-to-blood transport. METHODS: To detect an iRGD-induced tumour-to-blood transport, we examined the effect of intravenously injected iRGD on blood levels of α-fetoprotein (AFP) and autotaxin in several mouse models of hepatocellular carcinoma (HCC) or in mice with chronic liver injury without HCC, and on prostate-specific antigen (PSA) levels in mice with prostate cancer. FINDINGS: Intravenously injected iRGD rapidly and robustly elevated the blood levels of AFP in several mouse models of HCC, but not in mice with chronic liver injury. The effect was primarily seen in mice with small tumours and normal basal blood AFP levels, was attenuated by an anti-neuropilin-1 antibody, and depended on the concentration gradient between tumour and blood. iRGD treatment was also able to increase blood levels of autotaxin in HCC mice, and of PSA in mice with prostate cancer. INTERPRETATION: We conclude that iRGD induces a tumour-to-blood transport in a tumour-specific fashion that has potential of improving diagnosis of early stage cancer. FUNDING: Deutsche Krebshilfe, DKTK, LOEWE-Frankfurt Cancer Institute.


Asunto(s)
Biomarcadores de Tumor , Carcinoma Hepatocelular , Modelos Animales de Enfermedad , Neoplasias Hepáticas , Hidrolasas Diéster Fosfóricas , Animales , Ratones , Biomarcadores de Tumor/sangre , Hidrolasas Diéster Fosfóricas/sangre , Hidrolasas Diéster Fosfóricas/metabolismo , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/metabolismo , alfa-Fetoproteínas/metabolismo , Masculino , Humanos , Línea Celular Tumoral , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Oligopéptidos/administración & dosificación
2.
J Transl Med ; 22(1): 427, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38711144

RESUMEN

BACKGROUND: Circular RNAs (circRNAs), one of the major contents of exosomes, have been shown to participate in the occurrence and progression of cancers. The role and the diagnostic potential of exosome-transported circRNAs in non-small-cell lung cancer (NSCLC) remain largely unknown. METHODS: The NSCLC-associated exosomal circ_0061407 and circ_0008103 were screened by circRNA microarray. The role of circ_0061407 and circ_0008103 in NSCLC was examined in vitro and in vivo. The encapsulation of the two circRNAs into exosomes and the transport to recipient cells were observed by confocal microscopy. The effects of exosome-transported circ_0061407 and circ_0008103 on recipient cells were investigated using a co-culture device. Bioinformatics analyses were performed to predict the mechanisms by which circ_0061407 and circ_0008103 affected NSCLC. The quantitative polymerase chain reaction was used to quantify the exosome-containing circ_0061407 and circ_0008103 in the serum samples of healthy, pneumonia, benign lung tumours, and NSCLC. The diagnostic efficacy was evaluated using receiver operating characteristic curves. RESULTS: The levels of circ_0061407 and circ_0008103 within exosomes were down-regulated in the serum of patients with NSCLC. The up-regulation of circ_0061407 and circ_0008103 inhibited the proliferation, migration/invasion, cloning formation of NSCLC cells in vitro and inhibited lung tumour growth in vivo. Circ_0061407 and circ_0008103 were observed to be packaged in exosomes and transported to recipient cells, where they inhibited the proliferation, migration/invasion, and cloning formation abilities of the recipient cells. Moreover, circ_0061407 and circ_0008103 might be involved in the progression of NSCLC by interacting with microRNAs and proteins. Additionally, lower serum exosomal circ_0061407 and circ_0008103 levels were associated with advanced pathological staging and distant metastasis. CONCLUSIONS: This study identified two novel exosome-transported circRNAs (circ_0061407 and circ_0008103) associated with NSCLC. These findings may provide additional insights into the development of NSCLC and potential diagnostic biomarkers for NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Exosomas , Neoplasias Pulmonares , ARN Circular , Exosomas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/sangre , ARN Circular/genética , ARN Circular/sangre , ARN Circular/metabolismo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/sangre , Animales , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Masculino , Regulación Neoplásica de la Expresión Génica , Femenino , Ratones Desnudos , Persona de Mediana Edad , Ratones Endogámicos BALB C , Curva ROC , Ratones
3.
J Exp Clin Cancer Res ; 43(1): 20, 2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38229152

RESUMEN

BACKGROUND: Extracellular vesicles (EVs) participate in cancer development via cell-to-cell communication. Long non-coding RNAs (lncRNAs), one component of EVs, can play an essential role in non-small-cell lung cancer (NSCLC) through EV-mediated delivery. METHODS: The NSCLC-associated lncRNA AL139294.1 in EVs was identified via lncRNA microarray analysis. The role of AL139294.1 in NSCLC was examined in vitro and in vivo. Confocal microscopy was used to observe the encapsulation of AL139294.1 into EVs and its transport to recipient cells. A co-culture device was used to examine the effects of transported AL139294.1 on the oncogenic behaviour of recipient cells. Dual-luciferase reporter assay was performed to verify the direct interaction of miR-204-5p with AL139294.1 and bromodomain-containing protein 4 (BRD4). AL139294.1 and miR-204-5p in EVs were quantified using quantitative polymerase chain reaction. Receiver operating characteristic analyses were conducted to evaluate the diagnostic efficiency. RESULTS: The lncRNA AL139294.1 in EVs promoted NSCLC progression in vitro and in vivo. After AL139294.1 was encapsulated into EVs and transported to recipient cells, it promoted the cells' proliferation, migration, and invasion abilities by competitively binding with miR-204-5p to regulate BRD4, leading to the activation of the Wnt and NF-κB2 pathways. Additionally, the expression of serum lncRNA AL139294.1 in EVs was increased, whereas miR-204-5p in EVs was decreased in NSCLC. High levels of lncRNA AL139294.1 and low levels of miR-204-5p in EVs were associated with advanced pathological staging, lymph node metastasis, and distant metastasis, underscoring their promising utility for distinguishing between more and less severe manifestations of the disease. CONCLUSIONS: This study reveals a novel lncRNA in EVs associated with NSCLC, namely, AL139294.1, providing valuable insights into the development of NSCLC and introducing potential diagnostic biomarkers for NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Vesículas Extracelulares , Neoplasias Pulmonares , MicroARNs , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Subunidad p52 de NF-kappa B , Proteínas Nucleares , Neoplasias Pulmonares/genética , Factores de Transcripción , Proliferación Celular , MicroARNs/genética , Proteínas que Contienen Bromodominio , Proteínas de Ciclo Celular
4.
Cancer Control ; 31: 10732748241228037, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38246662

RESUMEN

BACKGROUND: Pancreatic cancer is a challenging disease, often requiring invasive procedures for diagnosis. Reliable tumour markers are essential for ensuring early detection and better patient outcomes. Although Carbohydrate Antigen 19-9 is the most commonly used marker, it is marred by low predictive accuracy and high false positivity. Carcino Embryonic Antigen also has limited practical use. A novel antigen, Cytokeratin fragment 21-1, is gaining significance for its diagnostic value in various tumours. MATERIALS AND METHODS: This prospective study aimed to evaluate the potential of Cytokeratin fragment 21-1 in comparison with Carbohydrate Antigen 19-9 and Carcino Embryonic Antigen in diagnosing pancreatic cancer. From January 2016 to December 2019, 45 patients with confirmed pancreatic ductal adenocarcinoma were included in this cross-sectional study. RESULTS: Carbohydrate Antigen 19-9 was raised in 22 patients, Carcino Embryonic Antigen was elevated in 17, and Cytokeratin fragment 21-1 was elevated in 30 cases. Carbohydrate Antigen 19-9 was found to be elevated in the presence of jaundice. Both Carbohydrate Antigen 19-9 and Cytokeratin fragment 21-1 had good correlation with stage of cancer, while Carcino Embryonic Antigen had very minimal correlation. CONCLUSION: In this study, Cytokeratin fragment 21-1 was elevated in a higher number of cases than Carbohydrate Antigen 19-9 and Carcino Embryonic Antigen. Both Cytokeratin fragment 21-1 and Carbohydrate Antigen 19-9 correlated well with cancer stage. Also Cytokeratin fragment 21-1 was not affected by jaundice, unlike Carbohydrate Antigen 19-9. Therefore, Cytokeratin fragment 21-1 has the potential to be an effective individual tumour marker in pancreatic cancer.


Asunto(s)
Antígenos de Neoplasias , Carcinoma Ductal Pancreático , Ictericia , Neoplasias Pancreáticas , Humanos , Estudios Transversales , Estudios Prospectivos , Neoplasias Pancreáticas/diagnóstico , Carcinoma Ductal Pancreático/diagnóstico , Queratina-19 , Biomarcadores de Tumor , Carbohidratos
5.
Ann Clin Biochem ; 61(4): 265-272, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38111979

RESUMEN

BACKGROUND: CA19-9 is elevated in pancreatic cancer and other malignancies, and commonly used in clinical practice. Unfortunately, CA19-9 immunoassays are not harmonized, and reference intervals may differ between assays. The aim of this study was to establish the reference interval of the ADVIA Centaur/Atellica IM CA19-9 assay in an apparently healthy Singapore adult population. METHODS: This is a retrospective cross-sectional study. De-identified data from Health Screening participants were extracted from our database. Subjects with biochemical results suggesting anaemia, diabetes mellitus, viral hepatitis or abnormal liver, and renal and tumour markers were excluded. Outlier and subclass analyses by age and sex were performed. CA19-9 reference limits and 90% confidence intervals were then determined for candidate subclasses. RESULTS: Data from 12,174 subjects (5846 males and 6328 females) were available after exclusion criteria were applied. CA19-9 results did not follow a normal distribution and were higher in females compared to males (P < .001). Although CA19-9 means were statistically different between certain age groups, the evaluable 99th percentile reference limits were not statistically different. The overall 99th percentile reference limits for the Centaur/Atellica CA19-9 assay was 37 U/mL for males 21-80 years, and 60 U/mL for females 21-80 years. CONCLUSIONS: Our results suggest that separate CA19-9 reference intervals should be applied for males and females.


Asunto(s)
Antígeno CA-19-9 , Humanos , Masculino , Femenino , Singapur , Adulto , Persona de Mediana Edad , Valores de Referencia , Antígeno CA-19-9/sangre , Anciano , Estudios Retrospectivos , Estudios Transversales , Adulto Joven , Anciano de 80 o más Años
7.
J Oral Maxillofac Pathol ; 27(2): 427, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37854911

RESUMEN

Background: Epithelial membrane antigen (EMA) has been used as a marker for the expression of tumour margins in various glandular neoplastic lesions. Histopathologically, oral squamous cell carcinoma (OSCC) may exhibit several features within the same tumour cells, portraying that these cells at the invasive margins commonly display certain features that differ from those of the superficial part of the tumour. Aim: To identify and study the invasive tumour front and also to recognise any micrometastases in an OSCC lesion. Materials and Method: A retrospective study of 30 OSCC cases with superficial and most invasive parts were sectioned at 4 µm. Routine H&E staining and immunohistochemical staining with mouse antihuman EMA were done. The OSCC cases were graded into well differentiated squamous cell carcinoma (WDSCC), moderately differentiated squamous cell carcinoma (MDSCC) and poorly differentiated squamous cell carcinoma (PDSCC). The EMA-stained slides were observed and analysed under higher magnification to identify the individual EMA-stained cells. Results: Analysis of Variance (ANOVA) analysis revealed that when comparing the superficial and invasive fronts of OSCC, it was evident that the P values were significant across the groups. In WDSCC, positive predictive value was 70.6% and sensitivity was 100% when the same slide was analysed for large and small islands to individual cells in an EMA-stained section, while MDSCC and PDSCC showed both sensitivity and positive predictive value to be 100%. Conclusion: EMA could be considered a useful prognostic marker for describing the nature of the neoplastic epithelium as well as recognising the typical anaplastic cells in cases of OSCC.

8.
Phys Med Biol ; 68(18)2023 09 08.
Artículo en Inglés | MEDLINE | ID: mdl-37681308

RESUMEN

Objective.The results of a follow-up experiment investigating a novel method for sub-milimetre range verification (RV) in proton therapy (PT) are presented.Approach.The method consists of implanting a hadron tumour marker (HTM) near the planned treatment volume, and measuring theγ-ray signals emitted as a result of activation by the proton beam. These signals are highly correlated with the energy of the beam impinging on the HTM and can provide an absolute measurement of the range of the beam relative to the position of the HTM, which is independent of any uncertainties in beam delivery.Main results.Three candidate HTM materials were identified and combined into a single composite HTM, which makes use of the strongest reaction in each material. The setup of the previous experiment was improved on by using high-purity germanium detectors to measure theγ-ray signal with a higher resolution than was previously achieved. A PMMA phantom was also used to simulate theγ-ray background from tissue activation. HTM RV using the data collected in this study yielded range measurements whose average deviation from the expected value was 0.13(22)mm.Significance.Range uncertainty in PT limits the prescribed treatment plan for cancer patients with large safety margins and constrains the direction of the proton beam in relation to any organ at risk. The sub-milimetre range uncertainty achieved in this study using HTM RV, if implemented clinically, would allow for a reduction in the size of safety margins, increasing the therapeutic window for PT.


Asunto(s)
Germanio , Terapia de Protones , Humanos , Protones , Biomarcadores de Tumor , Fantasmas de Imagen
9.
Phys Med Biol ; 68(19)2023 09 25.
Artículo en Inglés | MEDLINE | ID: mdl-37747082

RESUMEN

Objective.A new method to estimate the range of an ion beam in a patient during heavy-ion therapy was investigated, which was previously verified for application in proton therapy.Approach.The method consists of placing a hadron tumour marker (HTM) close to the tumour. As the treatment beam impinges on the HTM, the marker undergoes nuclear reactions. When the HTM material is carefully chosen, the activation results in the emission of several delayed, characteristicγrays, whose intensities are correlated with the remaining range inside the patient. When not just one but two reaction channels are investigated, the ratio between these twoγray emissions can be measured, and the ratio is independent of any beam delivery uncertainties.Main results.A proof-of-principle experiment with an16O ion beam and Ag foils as HTM was successfully executed. The107Ag(16O,x)112Sb and the107Ag(16O,x)114Sb reaction channels were identified as suitable for the HTM technique. When only oneγ-ray emission is measured, the resulting range-uncertainty estimation is at the 0.5 mm scale. When both channels are considered, a theoretical limit on the range uncertainty of a clinical fiducal marker was found to be ±290µm.Significance.Range uncertainty of a heavy-ion beam limits the prescribed treatment plan for cancer patients, especially the direction of the ion beam in relation to any organ at risk. An easy to implement range-verification technique which can be utilized during clinical treatment would allow treatment plans to take full advantage of the sharp fall-off of the Bragg peak without the risk of depositing excessive dose into healthy tissue.


Asunto(s)
Radioterapia de Iones Pesados , Terapia de Protones , Humanos , Biomarcadores de Tumor , Radioterapia de Iones Pesados/métodos , Terapia de Protones/métodos , Incertidumbre , Método de Montecarlo
10.
Afr J Lab Med ; 12(1): 2027, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37434992

RESUMEN

Background: Inappropriate testing remains a high healthcare cost driver. Tumour marker tests are more expensive than routine chemistry testing. Implementing test demand management systems like electronic gatekeeping (EGK) has reportedly decreased test requests. Objective: This study aimed to describe the appropriateness of tumour marker tests, carcinoembryonic antigen, alpha foetal protein, prostate-specific antigen, carbohydrate antigen 19-9, cancer antigen 15-3, cancer antigen 125, and human chorionic gonadotropin, and determine the effectiveness of the EGK used in the public health sector in KwaZulu-Natal, South Africa. Methods: Tumour marker test data for the KwaZulu-Natal province were extracted from the National Health Laboratory Service Central Data Warehouse for 01 January 2017 - 30 June 2017 (pre-EGK) and 01 January 2018 - 30 June 2018 (post-EGK implementation). Questionnaires were sent to the clinicians in the regional hospitals ordering the most tumour marker tests to assess ordering practices. In addition, we assessed monthly rejection reports to determine the effect of the EGK. Results: The EGK minimally reduced tumour marker requests or associated costs (1.4% average EGK rejection rate). An overall 18% increase in the tumour marker tests occurred in 2018. The data suggest inappropriate tumour marker test utilisation, particularly for screening. Conclusion: The introduction of EGK as a test demand management had little impact on tumour marker test requests and costs. Continuous education and reiteration of indications for tumour marker test use are required. What this study adds: This study demonstrates the ineffectiveness of EGK in tumour marker orders, and provides some insight as to why these markers are being ordered, which is important in trying to decrease inappropriate ordering of these tests.

11.
J Oral Maxillofac Pathol ; 27(1): 98-102, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37234320

RESUMEN

Background: Cytokeratins are the largest sub-group of intermediate filaments and represent the most abundant proteins in epithelial cells. CYFRA 21-1 (human cytokeratin fragment antigen 21-1) is a soluble fragment of cytokeratin 19 known to increase in various malignancies. Aim: The present study is aimed to estimate salivary and serum levels of CYFRA 21-1 in oral squamous cell carcinoma (OSCC) patients and to compare them with healthy controls. Settings and Design: A prospective, case-control study. Material and Methods: This study included a total of 80 subjects, comprising 40 OSCC patients and 40 healthy controls. Saliva and blood samples were collected from the study population, and serum and salivary CYFRA 21-1 levels were measured by enzyme-linked immunosorbent assay. Statistical Analysis Used: The statistical tests applied were independent t-test, ANOVA test for comparison, and Post hoc test for correlation. A P value of < 0.05 was considered statistically significant. Results: A statistically significant increase in salivary and serum CYFRA 21-1 levels was observed between OSCC and control groups and with an increase in the pathological tumour node metastasis stage and histopathological grade of OSCC. On correlating salivary and serum CYFRA 21-1 values, there were 3-fold higher salivary levels than serum. Conclusion: CYFRA 21-1 can be suggested as a tumour marker that can be used for the early diagnosis of the OSCC. Further prospective studies with a larger sample size and advanced techniques recommended before CYFRA 21-1 can be recommended for routine clinical use.

12.
J Oral Maxillofac Pathol ; 27(1): 39-48, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37234325

RESUMEN

Introduction: Squamous cell carcinoma-related antigen is not always sensitive enough for the early detection of oral cancer which is why a new marker has been desired as a substitute to be applied for serum diagnosis of oral cancer. Reactive oxygen species (ROS) has been known to play an important role in carcinogenesis. Glutathione-s-transferases (GSTs) are a family of eukaryotic and prokaryotic phase-II metabolic isoenzymes involved in xenobiotic detoxification. This correlation of the ROS species function and their role in initiation and progression of cancer could be exploited as of diagnostic value. The biologic function of the GSTs in human head-and-neck squamous cell carcinomas has been studied by researchers at gross as well as molecular levels. Taking into consideration this scientific background, future scope and perspectives, we initiated this study. Materials and Methods: This study was performed as a prospective case-control in vitro analytical study with subjects (n = 40) fulfilling the prerequisite conditions and were compliant. The case group (n = 20) was subjects with histopathologically proven cases of oral malignancy and age- and sex-matched control group (n = 20). The enzyme GST was evaluated in sera of all participants and then comparison was done between two groups as well as correlation with histopathologic grading for oral malignancy. Results: The mean serum GST activity in oral cancer patients was significantly higher than that of the control group. The present study has compared the alterations of enzyme in relation to histopathological grading of oral malignancy and found increased serum GST activity of well-differentiated and moderately differentiated carcinomas than the poorly differentiated carcinoma in terms of mean. Conclusion: Increased expression of the enzyme, as reported in the present study, can be due to tumor burden which attributes to overproduction of GST by cancer cells. The major clinical significance of the present study is that it gives important information regarding a new tumor progression and prognosis marker.

13.
Clin Chem Lab Med ; 61(10): 1841-1849, 2023 09 26.
Artículo en Inglés | MEDLINE | ID: mdl-37078204

RESUMEN

OBJECTIVES: We tested the hypothesis that the free-ß subunit (ßhCG) is diagnostically more sensitive with total hCG assays (hCGt) not detecting all tumours secreting ßhCG. The effects of sex, age, and renal failure were investigated as secondary objectives. METHODS: We compared ßhCG with hCGt in 204 testicular cancer patients (99 seminomas, 105 non-seminonatous germ cell tumours). The effects of sex and age were determined in 125 male and 138 female controls and that of renal failure was investigated in 119 haemodialysis patients. Biochemical assessment of gonadal status was performed with LH, FSH, oestradiol and testosterone. RESULTS: Discordant results were common with isolated increases of hCGt observed in 32 (15.7 %) and ßhCG in 14 (6.9 %) patients. Primary hypogonadism was the most common cause of isolated hCGt increases. After therapeutic interventions ßhCG decreased below its upper reference more rapidly than hCGt. We observed unequivocal false negative results in two patients with non-seminomatous germ cell tumours. Both occurred in patients with clinical tumour recurrences; in one instance we observed a false negative hCGt while in the second false negative ßhCG's were documented in serial samples. CONCLUSIONS: The similar false negative rates did not support the hypothesis that ßhCG will detect more patients with testicular cancer than hCGt. In contrast to hCGt, ßhCG was unaffected by primary hypogonadism which is a predictably frequent complication in testicular cancer patients. We therefore recommend ßhCG as the preferred biomarker in testicular cancer.


Asunto(s)
Hipogonadismo , Neoplasias de Células Germinales y Embrionarias , Seminoma , Neoplasias Testiculares , Adulto , Femenino , Humanos , Masculino , Gonadotropina Coriónica , Gonadotropina Coriónica Humana de Subunidad beta , Recurrencia Local de Neoplasia , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Seminoma/diagnóstico , Neoplasias Testiculares/diagnóstico
14.
Clin Chem Lab Med ; 61(10): 1829-1840, 2023 09 26.
Artículo en Inglés | MEDLINE | ID: mdl-36994761

RESUMEN

OBJECTIVES: Few studies have reported on delta checks for tumour markers, even though these markers are often evaluated serially. Therefore, this study aimed to establish a practical delta check limit in different clinical settings for five tumour markers: alpha-fetoprotein, cancer antigen 19-9, cancer antigen 125, carcinoembryonic antigen, and prostate-specific antigen. METHODS: Pairs of patients' results (current and previous) for five tumour markers between 2020 and 2021 were retrospectively collected from three university hospitals. The data were classified into three subgroups, namely: health check-up recipient (subgroup H), outpatient (subgroup O), and inpatient (subgroup I) clinics. The check limits of delta percent change (DPC), absolute DPC (absDPC), and reference change value (RCV) for each test were determined using the development set (the first 18 months, n=179,929) and then validated and simulated by applying the validation set (the last 6 months, n=66,332). RESULTS: The check limits of DPC and absDPC for most tests varied significantly among the subgroups. Likewise, the proportions of samples requiring further evaluation, calculated by excluding samples with both current and previous results within the reference intervals, were 0.2-2.9% (lower limit of DPC), 0.2-2.7% (upper limit of DPC), 0.3-5.6% (absDPC), and 0.8-35.3% (RCV99.9%). Furthermore, high negative predictive values >0.99 were observed in all subgroups in the in silico simulation. CONCLUSIONS: Using real-world data, we found that DPC was the most appropriate delta-check method for tumour markers. Moreover, Delta-check limits for tumour markers should be applied based on clinical settings.


Asunto(s)
Biomarcadores de Tumor , Antígeno Prostático Específico , Masculino , Humanos , Estudios Retrospectivos , Antígeno Carcinoembrionario , Valores de Referencia , Antígeno Ca-125
15.
J Med Life ; 16(2): 186-188, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36937484

RESUMEN

Serological analysis of tumor markers has emerged as a non-invasive method for monitoring cancer patients, including tumor recurrence and response to treatment. Tumor markers have the potential to aid in both the diagnosis and prognosis of cancer, but their most important role currently lies in the monitoring of tumor progression. Tumor markers can also provide valuable information on treatment effectiveness, with changes in plasma values indicating tumor regression or progression. This research aimed to investigate the correlation between the serum detection values of three tumor markers - CEA, CA 19-9, and CA 72-4 - and their utility in the diagnosis and prognosis of patients with gastric cancer. The study seeks to uncover the relationship between these tumor markers and the evolution of gastric cancer, providing insights into their potential use in clinical practice.


Asunto(s)
Antígenos de Carbohidratos Asociados a Tumores , Neoplasias Gástricas , Humanos , Antígenos de Carbohidratos Asociados a Tumores/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Antígeno Carcinoembrionario , Recurrencia Local de Neoplasia , Antígeno CA-19-9/uso terapéutico , Biomarcadores de Tumor , Pronóstico
16.
BMC Cancer ; 23(1): 291, 2023 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-36997875

RESUMEN

BACKGROUND: To unravel how the integrity of nuclear and mitochondrial circulating cell-free DNA (cfDNA) contributes to its plasma quantity in colorectal cancer (CRC) patients. METHODS: CfDNA from plasma samples of 80 CRC patients stratified by tumour stage and 50 healthy individuals were extracted. Total cfDNA concentration was determined and equal template concentrations (ETC) were analyzed by quantitative real-time PCR (qPCR) resulting in small and long fragments of KRAS, Alu and MTCO3. The obtained data was also examined relative to the total cfDNA concentration (NTC) and diagnostic accuracy was estimated using receiver operating characteristics. RESULTS: Total cfDNA levels were significantly higher in CRC group compared to healthy control and increased with tumour stage. Long nuclear fragment levels were significantly lower in CRC patients in ETC but not NTC condition. The integrity indices of nuclear cfDNA decreased from controls to patients with highly malignant tumor. Mitochondrial cfDNA fragment quantities were strongly reduced in early and late stages of tumor patients and prognostic value was higher in ETC. Predictive models based on either ETC or NTC predictor set showed comparable classification performance. CONCLUSION: Increased blood cfDNA concentration in late UICC stages inversely correlate with nuclear cfDNA integrity index and suggest that necrotic degradation is not a major cause for higher total cfDNA quantity. The diagnostic and prognostic value of MTCO3 is highly significant in early stages of CRC and can be evaluated more comprehensively, using ETC for qPCR analysis. TRIAL REGISTRATION: The study was registered retrospectively on DRKS, the german register for clinical trials (DRKS00030257, 29/09/2022).


Asunto(s)
Ácidos Nucleicos Libres de Células , Neoplasias Colorrectales , Humanos , Estudios Retrospectivos , Detección Precoz del Cáncer , Pronóstico , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Biomarcadores de Tumor/genética
17.
Pediatr Blood Cancer ; 70(3): e30117, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36451268

RESUMEN

BACKGROUND: Chemotherapy for non-seminomatous germ cell tumours (NSGCT) exposes to dose-dependent toxicities. The TGM13-NS protocol (EudraCT 2013-004039-60) aimed to decrease the chemotherapy burden compared to the previous TGM95 protocol while maintaining the 5-year event-free survival (EFS) at 80% or more. PROCEDURE: Patients less than 19 years of age with disseminated NSGCT were enrolled (May 2014 to May 2019) and stratified into four groups: two intermediate-risk (IR: localised tumour with low tumour markers [TM]) groups treated with VBP (vinblastine-bleomycin-cisplatin): three courses for IR1 (ovarian tumour any age/testis tumour less than or equal to 10 years) and four courses for IR2 (extragonadal tumour 10 years or less) groups, and two high-risk (HR: metastatic and/or high TM) groups treated with etoposide-cisplatin and either ifosfamide (VIP) or bleomycin (BEP): three courses for HR1 (ovarian tumour any age/testis tumour less than or equal to 10 years and low TM/testis tumour more than 10 years and very low TM) groups and four courses for HR2 (remainder) groups. RESULTS: One hundred fifteen patients were included: median age of 12.8 years (0.4-18.9); tumour sites: 44 ovaries, 37 testes and 34 extragonadal. The 5-year EFS and overall survival (OS) were 87% (95% CI: 80-92) and 95% (89-98), respectively (median follow-up: 3.5 years, range: 0.2-5.9), similar to those of the TGM95 protocol (5-year EFS 89% (84-93), 5-year OS 93% (89-95), p = .561). The 5-year EFS were 93% (95% CI: 80-98), 88% (71-95) and 79% (62-90) for ovarian, testicular and extragonadal tumours, respectively. The 5-year EFS varied (p = .02) according to the risk groups: 90% (66-97), 64% (30-85), 95% (72-99) and 87% (74-94) for IR1, IR2, HR1 and HR2, respectively. TM decline adjusted to tumour site, and alpha-fetoprotein (AFP) level revealed a prognostic impact of time to normalisation on EFS: HR = 1.03 (1.003-1.007). CONCLUSION: Risk-adapted and globally decreased chemotherapy burden maintains excellent outcomes, exclusive of the IR2 group, which warrants more intensive chemotherapy.


Asunto(s)
Neoplasias de Células Germinales y Embrionarias , Neoplasias Ováricas , Neoplasias Testiculares , Masculino , Femenino , Humanos , Niño , Adolescente , Cisplatino , Etopósido , Neoplasias Testiculares/patología , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bleomicina , Pronóstico , Biomarcadores de Tumor
18.
J Ayub Med Coll Abbottabad ; 35(Suppl 1)(4): S710-S714, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38406898

RESUMEN

Background: The most common malignancy and second most common cause of death is breast cancer among women. About 2.09 million fatalities from breast cancer happened in 2018. The objective was to evaluate the elevated CA15-3 in breast cancer patients with visceral metastases presenting at the tertiary care hospital of Karachi. Methods: It was a cross-sectional study conducted at the Department of Oncology of Jinnah Postgraduate Medical Center from 15th December 2018 to 15th November 2019. Female patients aged 26-80 years diagnosed with visceral metastatic (defined as metastasis to lung, liver, brain and adrenal glands) breast cancer were included in the study. The diagnosis of breast cancer was confirmed on histopathology whereas the metastatic sites were evaluated using physical examination and imaging. The serum CA15-3 concentration was assessed using assay kits. The serum CA15-3 level of 0-32 U/ml was taken as normal range for all the patients whereas CA15-3 level greater than 32 U/L was considered as elevated CA15-3. SPSS version 23 was used to enter and analyze data. Results: A total of 139 females were included in the study. The mean age & BMI of the patients were reported as 46.5 years & 26.69 kg/m2. In the majority of the patients' metastases were detected in the liver (n=54), 92 in the lungs+ parenchymal disease, 20 in adrenal glands, 12 in pleural effusion and 10 in the brain. Out of 139 patients with visceral metastases, 52(37.4%) had normal CA15-3 level whereas 87 (62.6%) had elevated serum CA15-3 levels (>32 U/L). Conclusion: The serum CA15-3 tumour marker is elevated significantly in visceral metastases and can be used as a prognostic marker in metastatic breast cancer patients.


Asunto(s)
Neoplasias de la Mama , Carcinoma , Femenino , Humanos , Persona de Mediana Edad , Estudios Transversales , Mucina-1 , Biomarcadores de Tumor , Neoplasias de la Mama/diagnóstico , Pronóstico
19.
Curr Oncol ; 29(12): 9916-9927, 2022 12 16.
Artículo en Inglés | MEDLINE | ID: mdl-36547194

RESUMEN

(1) Background: As genomic testing is becoming a part of the mainstream oncology practice, it is vital to ensure that our patients fully understand the implications of these tests. This study aimed to compare the attitudes and expectations of cancer patients with those of their physicians regarding the role of biomarker testing in clinical decision making. (2) Methods: Two separate, complimentary, self-administered questionnaires for patients with cancer and their physicians, respectively, were collected in Calgary, Alberta, Canada. Out of 117, 113 completed patient surveys were included in the statistical analysis, constituting a 96.4% response rate. These surveys were subsequently matched with those of their corresponding oncologists to determine the concordance rates. (3) Results: Overall, patients demonstrated a good understanding of general cancer biology (80.0%) and diagnostic processes (90.0%) associated with precision oncology. Most patients wanted their tumours to be tested to guide treatment, and the oncologists broadly shared these views (concordance 65.1%). However, there were discrepancies between the knowledge and expectations regarding the applications of test results on actual diagnosis and prognosis between patients and their oncologists (concordance 26.1% and 36.0%, respectively). While only 28.0% of patients thought they had enough knowledge to make informed decisions, the majority (68.0%) said they needed more information. (4) Conclusion: Our study shows that patients and cancer physicians do not always agree with the roles and applications of genomic tests, which could lead to misplaced expectations and poor health outcomes. More research is needed to devise strategies to improve education and communication to align these expectations and improve the quality of clinical decision making.


Asunto(s)
Neoplasias , Médicos , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/terapia , Motivación , Medicina de Precisión , Alberta
20.
Rozhl Chir ; 101(10): 469-477, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36402558

RESUMEN

Renal cell carcinoma represents 23% of all adult malignancies and its incidence in the Czech Republic is one of the highest worldwide. Until late stages this disease often remains asymptomatic, which makes its diagnosis difficult. Despite an increasing proportion of small, incidentally detected tumours on imaging, approximately one third of patients are still diagnosed with advanced disease. Moreover, a relapse occurs in up to 40% of patients after surgery for localized tumour. Increased availability of imaging investigations allowing an early detection of kidney carcinoma and advances in systemic treatment have favourably affected the outcome of patients with this type of tumour. Nevertheless, mortality of renal cell carcinoma remains the highest among urological malignancies. The individual course of the disease and its response to systemic treatment are difficult to predict. A number of prognostic factors of renal cell carcinoma have been identified, of which TNM classification and tumour grade remain the most important. Recently, several multivariate prognostic models have become available, allowing a more accurate prediction of the disease course. In localized disease, they are useful in identifying patients at higher risk of recurrence and allow optimization of follow-up after surgery. In metastatic disease, they are routinely used to stratify patients into risk groups for targeted treatment. There has been a long-term effort to identify a suitable biomarker useful for an early detection and assessment of the prognosis of renal cell carcinoma. At the same time, such a biomarker could improve the accuracy of established prognostic systems. This text presents an overview of prognostic factors of renal cell carcinoma, including a summary of potential biomarkers.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Adulto , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/cirugía , Pronóstico , Recurrencia Local de Neoplasia , Neoplasias Renales/diagnóstico , Neoplasias Renales/cirugía , Neoplasias Renales/patología , Biomarcadores
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