The diagnostic workup of individuals suspected of having lung cancer can be complex and protracted because conventional symptoms of lung cancer have low specificity and sensitivity.
Among individuals ...with symptoms of lung cancer, can a blood-based approach to analyze cell-free DNA (cfDNA) fragmentation (the DNA evaluation of fragments for early interception DELFI score) enhance evaluation for the possible presence of lung cancer?
Adults were referred to Bispebjerg Hospital (Copenhagen, Denmark) for diagnostic evaluation of initial imaging anomalies and symptoms consistent with lung cancer. Numbers and types of symptoms were extracted from medical records. cfDNA from plasma samples obtained at the prediagnostic visit was isolated, sequenced, and analyzed for genome-wide cfDNA fragmentation patterns. The relationships among clinical presentation, cancer status, and DELFI score were examined.
A total of 296 individuals were analyzed. Median DELFI scores were higher for those with lung cancer (n = 98) than those without cancer (n = 198; 0.94 vs 0.19; P < .001). In a multivariate model adjusted for age, smoking history, and presenting symptoms, the addition of the DELFI score improved the prediction of lung cancer for those who demonstrated symptoms (area under the receiver operating characteristic curve, 0.74-0.94).
The DELFI score distinguishes individuals with lung cancer from those without cancer better than suspicious symptoms do. These results represent proof-of-concept support that fragmentation-based biomarker approaches may facilitate diagnostic resolution for patients with concerning symptoms of lung cancer.
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With the advent of precision oncology, there is an urgent need to develop improved methods for rapidly detecting responses to targeted therapies. Here, we have developed an ultrasensitive measure of ...cell-free tumor load using targeted and whole-genome sequencing approaches to assess responses to tyrosine kinase inhibitors in patients with advanced lung cancer. Analyses of 28 patients treated with anti-EGFR or HER2 therapies revealed a bimodal distribution of cell-free circulating tumor DNA (ctDNA) after therapy initiation, with molecular responders having nearly complete elimination of ctDNA (>98%). Molecular nonresponders displayed limited changes in ctDNA levels posttreatment and experienced significantly shorter progression-free survival (median 1.6 vs. 13.7 months,
< 0.0001; HR = 66.6; 95% confidence interval, 13.0-341.7), which was detected on average 4 weeks earlier than CT imaging. ctDNA analyses of patients with radiographic stable or nonmeasurable disease improved prediction of clinical outcome compared with CT imaging. These analyses provide a rapid approach for evaluating therapeutic response to targeted therapies and have important implications for the management of patients with cancer and the development of new therapeutics.
Cell-free tumor load provides a novel approach for evaluating longitudinal changes in ctDNA during systemic treatment with tyrosine kinase inhibitors and serves an unmet clinical need for real-time, noninvasive detection of tumor response to targeted therapies before radiographic assessment.
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•The rs1143627 and rs1946518 polymorphisms were noteworthy by Bayesian calculations.•There was a high degree of co-expression among IL1B, IL6, IL8 and PTGS2 genes.•The protein–protein network showed ...that IL-1B was co-expressed with IL-8.
Our study aimed to revaluate the significant data from meta-analyses on genetic variations in immune mediators and the risk of prostate cancer (PCa) by Bayesian approaches.
We performed a search on the literature before September 5th, 2023, for meta-analytic studies on polymorphisms in immune mediator genes and the risk of PCa. Two Bayesian approaches were used to assess the level of noteworthiness in the meta-analytic data: the False-Positive Rate Probability (FPRP) and the Bayesian False Discovery Probability (BFDP) with a statistical power of 1.2 and 1.5 of Odds Ratio at a prior probability of 10−3 and 10−6. The quality evaluation of studies was performed with the Venice criteria. Gene-gene and protein–protein networks were designed for the genes and products enrolled in the results.
As results, 18 meta-analyses on 17 polymorphisms in several immune mediator genes were included (IL1B rs16944/rs1143627, IL4 rs2243250/rs2227284/rs2070874, IL6 1800795/rs1800796/rs1800797, IL8 rs4073, IL10 rs1800896/rs1800871/rs1800872, IL18 rs1946518, COX2 rs2745557, TNFA rs361525 and PTGS2 rs20417/689470). The Bayesian calculations showed the rs1143627 and the rs1946518 polymorphisms in IL1B and IL18 genes, respectively, were noteworthy. The Venice criteria showed that only four studies received the highest level of evidence. The gene-gene and protein–protein networks reinforced the findings on IL1B and IL18 genes.
In conclusion, this current Bayesian revaluation showed that the rs1143627 and the rs1946518 polymorphisms in the IL1B and IL18 genes, respectively, were noteworthy biomarker candidates for PCa risk.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•The calculations showed specific SNPs as noteworthy for HCC risk.•The STAT4 and MDM2 genes have a central role in hepatocellular carcinoma.•The genes that were noteworthy are potential biomarkers ...for the disease.
Hepatocellular carcinoma (HCC) is considered as the second cause of cancer-related deaths worldwide. Genetic variations are associated with HCC risk, an issue that has been the subject of several meta-analyses. However, meta-analyses have an important limitation on the likelihood of false positive data. Henceforth, this study aimed to assess the level of noteworthiness in the meta-analyses by means of a Bayesian approach. A systematic search was performed for meta-analyses with associations between gene polymorphisms and HCC. The calculations for the False-Positive Rate Probability (FPRP) and the Bayesian False Discovery Probability (BFDP) were performed to assess the noteworthiness with a statistical power of 1.2 and 1.5 of Odds Ratio at a prior probability of 10−3 and 10−5. The quality of studies was evaluated by the Venice criteria. As additional analyses, the gene-gene and protein–protein networks were designed for these genes and products. As results, we found 33 meta-analytic studies on 45 polymorphisms occurring in 35 genes. A total of 1,280 values for FPRP and BFDP were obtained. Seventy-five for FPRP (5.86%) and 95 for BFDP (14.79%) were noteworthy. In conclusion, the polymorphisms in CCND1, CTLA4, EGF, IL6, IL12A, KIF1B, MDM2, MICA, miR-499, MTHFR, PNPLA3, STAT4, TM6SF2, and XPD genes were considered as noteworthy biomarkers for HCC risk.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The
genus (mainly
Martius,
Martius, and
Martius) has recently gained commercial and scientific notoriety due to the high nutritional value of its fruits, which are rich in polyphenols (phenolic acids ...and anthocyanins) and have potent antioxidant activity. These characteristics have contributed to the increased number of neuropharmacological evaluations of the three species over the last 10 years, especially açaí of the species
Martius. The fruits of the three species exert neuroprotective effects through the modulation of inflammatory and oxidative pathways and other mechanisms, including the inhibition of the mTOR pathway and protection of the blood-brain barrier, all of them intimately involved in several neuropathologies. Thus, a better understanding of the neuropharmacological properties of these three species may open new paths for the development of therapeutic tools aimed at preventing and treating a variety of neurological conditions.
Dengue fever is a clinical manifestation of dengue virus (DENV) infection well defined by the intense host immune response with the development of high fever, anorexia, headache and muscle pain. ...Several immune mediators are involved in the pathophysiology of DENV infection, in which polymorphisms in immune molecule genes contribute with the susceptibility and severity of the infection. Several meta-analyses are available with significant findings in the association between genetic variants in immune-mediator genes and dengue, though the results may be false positive. Hence, to solve this issue, we have performed a systematic revaluation with Bayesian approaches to verify the false positive rate in these results. A systematic search was performed for meta-analytic studies on the aforementioned issue. The calculations of false positive report probability (FPRP) and the Bayesian false-discovery probability (BFDP) at the prior probability of 10-3 and 10-6 have been performed. To verify the methodological quality of the studies included, the evaluation by the Venice criteria was applied. In addition, gene-gene and protein-protein networks were designed. As results, seven meta-analyses on genetic variants in several immune-inflammatory mediator genes and DENV infection comprise the results. Only the polymorphisms in the TNF, MICB, PLCE1, VDR, CD32 and HLA-A genes were considered as noteworthy. There was a heterogeneity profile for the results on Venice criteria indicating variability in the methodological quality. The gene-gene and protein-protein networks showed these immune mediators as relevant players in the disease. We suggest these polymorphisms as potential biomarkers for the pathogenesis and immune response against DENV.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Since the rising of coronavirus disease 2019 (COVID-19) pandemic, there is uncertainty regarding the impact of transmission to cancer patients. Evidence on increased severity for patients undergoing ...antineoplastic treatment is posed against deferring oncologic treatment. We aimed to evaluate the impact of COVID-19 pandemic on patient volumes in a cancer center in an epicenter of the pandemic.
Outpatient and inpatient volumes were extracted from electronic health record database. Two intervals were compared: pre-COVID-19 (March to May 2019) and COVID-19 pandemic (March to May 2020) periods.
The total number of medical appointments declined by 45% in the COVID-19 period, including a 56.2% decrease in new visits. There was a 27.5% reduction in the number of patients undergoing intravenous systemic treatment and a 57.4% decline in initiation of new treatments. Conversely, there was an increase by 309% in new patients undergoing oral chemotherapy regimens and a 5.9% rise in new patients submitted to radiation therapy in the COVID-19 period. There was a 51.2% decline in length of stay and a 60% reduction in the volume of surgical cases during COVID-19. In the stem cell transplant unit, we observed a reduction by 36.5% in length of stay and a 62.5% drop in stem cell transplants.
A significant decrease in the number of patients undergoing cancer treatment was observed after COVID-19 pandemic. Although this may be partially overcome by alternative therapeutic options, avoiding timely health care due to fear of getting COVID-19 infection might impact on clinical outcomes. Our findings may help support immediate actions to mitigate this hypothesis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Chronic periodontitis (CP) is an immune-inflammatory disease that promotes tissue damage around the teeth. Among the several inflammatory mediators that orchestrate the periodontitis, there is the ...interleukin (IL)-2. Genetic variations in IL2 gene may be associated with the risk and severity of the disease. Contrary results are available in the literature with inconclusive findings and none meta-analysis to gather these data.
A literature search was performed for studies published before June 11, 2019 in diverse scientific and educational databases. The data was extracted by two investigators and the statistical evaluation was performed by Review Manager statistical program with heterogeneity (I
) and Odds Ratio (OR) with 95% of Confidence Intervals (CI) calculations and a sensitive analysis to assess the accuracy of the obtained results. The publication bias was evaluated by Begg' and Egger's test with Comprehensive meta-analysis software. The value of P < 0.05 was considered as significant.
Five studies were identified in diverse ethnical groups with 1425 participants. The - 330 T/G polymorphism in IL2 gene was not significantly associated with CP in allelic evaluation (P > 0.05) as well as in the genotypic comparisons (P = 0.15). The Begg's test and the linear regression Egger's test did not show any evidence of publication bias risk (P > 0.05) which was corroborated by the absence of obvious asymmetry in Funnel plot graphic.
This meta-analysis showed a non-significant association between - 330 T/G polymorphism in IL2 gene and CP in any allelic evaluation.
Gastric Metastasis of Breast Cancer: A Case Series Dos Santos Fernandes, Gustavo; Batista Bugiato Faria, Luiza D; de Assis Pereira, Isadora ...
Rare tumors,
10/2016, Volume:
8, Issue:
3
Journal Article
Peer reviewed
Open access
Gastric metastasis is rare but it can be the initial symptom of cancer. The second leading cause of this type of metastasis is breast cancer. A lack of clinical signs and nonspecific side effects of ...the treatment of primary tumors can lead to the misdiagnosis of metastatic gastric cancer. Upper gastrointestinal endoscopy with biopsy and immunohistochemistry should be used for diagnosis. Treatment is palliative; it includes chemo, endocrine, and radiation therapies. Four patients with breast cancer and gastric metastasis were identified. All the patients tested positive for estrogen and progesterone receptors, and received chemotherapy and hormone therapy. One patient underwent surgery and two received radiation therapy. Patients with breast cancer and gastrointestinal symptoms should be investigated for gastric metastasis, given its morbidity and negative impact on quality of life.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Over 9 million people die of cancer each year worldwide, reflecting the unmet need for effective biomarkers for both cancer diagnosis and prognosis. Cancer diagnosis is complex because the majority ...of malignant tumors present with long periods of latency and lack of clinical presentation at early stages. During carcinogenesis, premalignant cells experience changes in their epigenetic landscapes, such as differential DNA methylation, histone modifications, nucleosome positioning, and higher orders of chromatin changes that confer growth advantage and contribute to determining the biologic phenotype of human cancers.
Recent progress in microarray platforms and next-generation sequencing approaches has allowed the characterization of abnormal epigenetic patterns genome wide in a large number of cancer cases. The sizable amount of processed data also comes with challenges regarding data management and assessment for effective biomarker exploration to be further applied in prospective clinical trials. Epigenetics-based single or panel tests of genes are being explored for clinical management to fulfill unmet needs in oncology. The advance of these tests to the clinical routine will depend on rigorous, extensive, and independent validation in well-annotated cohort of patients and commercial development of clinical routine-friendly and adequate procedures.
In this review we discuss the analytic validation of tissue and cell-free DNA-based epigenomic approaches for early cancer detection, diagnosis, and treatment monitoring and the clinical utility of candidate epigenetic alterations applied to colorectal, glioblastoma, breast, prostate, bladder, and lung cancer management.
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