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Hematology/oncology and Stem Cell... Mar 2021Vitamin D is a steroid hormone that exerts its actions through ligation of the vitamin D receptor (VDR), a transcription factor of the nuclear receptor family. VDR has... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vitamin D is a steroid hormone that exerts its actions through ligation of the vitamin D receptor (VDR), a transcription factor of the nuclear receptor family. VDR has not only physiologic actions in calcium metabolism but also several other cellular effects through extensive binding to the DNA and modification of genome expression. In cancer, it has neoplasia-suppressive effects and various mechanisms of action mediating cancer cell inhibition have been described. Vitamin D deficiency has been linked to increased risk of breast cancer. A role of the vitamin once the disease has been diagnosed is also probable.
METHODS
A systematic review and meta-analysis of studies that report on vitamin D levels (in the form of its main circulating metabolite, 25-hydroxyvitamin D [25-OHD]) in patients with newly diagnosed breast cancer was performed. Outcomes of interest included the levels of serum 25-OHD in patients with breast cancer, those of matched controlled, in studies that included controls, as well as respective percentages of patients and controls with deficient and insufficient 25-OHD levels.
RESULTS
A total of 25 studies (10 with controls and 15 without controls) provided data on the outcomes of interest. Populations from all continents, besides Australia, were represented in the studies. The mean level of 25-OHD in patients with breast cancer was 26.88 ng/mL (95% CI 22.8-30.96 ng/mL) and the mean level of 25-OHD in control patients was 31.41 ng/mL (95% CI 19.31-43.5 ng/mL). In the patients with breast cancer group, 45.28% (95% CI 24.37%-53.51%) had levels of 25-OHD below 20 ng/mL, whereas this percentage was 33.71% (95% CI 21.61%-45.82%) in controls. Similarly, 67.44% (95% CI 48.32%-86.55%) of patients with breast cancer had a baseline level of 25-OHD below 30 ng/mL, whereas this percentage was 33.71% (95% CI 21.61%-45.82%) in controls.
CONCLUSION
A high prevalence of vitamin D insufficiency is observed in patients with newly diagnosed breast cancer and may be linked pathophysiologically with breast cancer development or progression. Therapeutic benefits may be provided by manipulation of the vitamin D pathway in breast cancer.
Topics: Breast Neoplasms; Female; Humans; Vitamin D; Vitamin D Deficiency
PubMed: 33002425
DOI: 10.1016/j.hemonc.2020.08.005 -
Nature Communications Nov 2021FOLFIRINOX, a combination of chemotherapy drugs (Fluorouracil, Oxaliplatin, Irinotecan -FOI), provides the best clinical benefit in pancreatic ductal adenocarcinoma... (Meta-Analysis)
Meta-Analysis
FOLFIRINOX, a combination of chemotherapy drugs (Fluorouracil, Oxaliplatin, Irinotecan -FOI), provides the best clinical benefit in pancreatic ductal adenocarcinoma (PDAC) patients. In this study we explore the role of miRNAs (MIR) as modulators of chemosensitivity to identify potential biomarkers of response. We find that 41 and 84 microRNA inhibitors enhance the sensitivity of Capan1 and MiaPaCa2 PDAC cells respectively. These include a MIR1307-inhibitor that we validate in further PDAC cell lines. Chemotherapy-induced apoptosis and DNA damage accumulation are higher in MIR1307 knock-out (MIR1307KO) versus control PDAC cells, while re-expression of MIR1307 in MIR1307KO cells rescues these effects. We identify binding of MIR1307 to CLIC5 mRNA through covalent ligation of endogenous Argonaute-bound RNAs cross-linking immunoprecipitation assay. We validate these findings in an in vivo model with MIR1307 disruption. In a pilot cohort of PDAC patients undergoing FOLFIRONX chemotherapy, circulating MIR1307 correlates with clinical outcome.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; DNA Damage; Fluorouracil; Gene Expression Regulation, Neoplastic; Humans; Irinotecan; Kaplan-Meier Estimate; Leucovorin; MicroRNAs; Neoadjuvant Therapy; Outcome Assessment, Health Care; Oxaliplatin; Pancreatic Neoplasms
PubMed: 34795259
DOI: 10.1038/s41467-021-27099-6 -
Journal of Ovarian Research Mar 2017Mature cystic teratomas are usually found in the ovaries. They are bilateral in 10 to 15% of cases and multiple cystic teratomas may be present in one ovary. The aim of... (Review)
Review
BACKGROUND
Mature cystic teratomas are usually found in the ovaries. They are bilateral in 10 to 15% of cases and multiple cystic teratomas may be present in one ovary. The aim of this study is to clarify if development of mature cystic teratomas of the ovaries in a single host is metachronous or due to autoimplant or recurrence.
CASE PRESENTATION
We report a woman with bilateral mature cystic teratomas of the ovaries. DNA profiles of these teratomas were investigated via short tandem repeat (STR) analysis and methylation statuses were determined via methylation sensitive multiplex ligation-dependent probe amplification methods. The results showed that the cystic teratomas originated from different stages of oogonia or primary oocyte before germinal vesicle stage failure of meiosis I in female gametogenesis. Potentially relevant literature was searched in PubMed database. Cases of bilateral or multiple mature cystic teratomas of the ovaries were analyzed. To date, there has been no reported case of multiple mature cystic teratomas in which clarification of the origin was achieved using molecular genetic methods.
CONCLUSIONS
The results of this case study provide evidence of metachronous development of mature cystic teratomas of the ovaries and may serve as a reference in the management of patients following laparoscopic cystectomy.
Topics: Adult; DNA Copy Number Variations; DNA Methylation; Female; Genetic Loci; Humans; Loss of Heterozygosity; Microsatellite Repeats; Neoplasm Grading; Neoplasms, Second Primary; Ovarian Neoplasms; Sequence Analysis, DNA; Teratoma
PubMed: 28288660
DOI: 10.1186/s13048-017-0313-8 -
The Cochrane Database of Systematic... Mar 2022Complete deletion of both the short arm of chromosome 1 (1p) and the long arm of chromosome 19 (19q), known as 1p/19q codeletion, is a mutation that can occur in... (Review)
Review
BACKGROUND
Complete deletion of both the short arm of chromosome 1 (1p) and the long arm of chromosome 19 (19q), known as 1p/19q codeletion, is a mutation that can occur in gliomas. It occurs in a type of glioma known as oligodendroglioma and its higher grade counterpart known as anaplastic oligodendroglioma. Detection of 1p/19q codeletion in gliomas is important because, together with another mutation in an enzyme known as isocitrate dehydrogenase, it is needed to make the diagnosis of an oligodendroglioma. Presence of 1p/19q codeletion also informs patient prognosis and prediction of the best drug treatment. The main two tests in use are fluorescent in situ hybridisation (FISH) and polymerase chain reaction (PCR)-based loss of heterozygosity (LOH) assays (also known as PCR-based short tandem repeat or microsatellite analysis). Many other tests are available. None of the tests is perfect, although PCR-based LOH is expected to have very high sensitivity.
OBJECTIVES
To estimate the sensitivity and specificity and cost-effectiveness of different deoxyribonucleic acid (DNA)-based techniques for determining 1p/19q codeletion status in glioma.
SEARCH METHODS
We searched MEDLINE, Embase and BIOSIS up to July 2019. There were no restrictions based on language or date of publication. We sought economic evaluation studies from the results of this search and using the National Health Service Economic Evaluation Database.
SELECTION CRITERIA
We included cross-sectional studies in adults with glioma or any subtype of glioma, presenting raw data or cross-tabulations of two or more DNA-based tests for 1p/19q codeletion. We also sought economic evaluations of these tests.
DATA COLLECTION AND ANALYSIS
We followed procedures outlined in the Cochrane Handbook for Diagnostic Test Accuracy Reviews. Two review authors independently screened titles/abstracts/full texts, performed data extraction, and undertook applicability and risk of bias assessments using QUADAS-2. Meta-analyses used the hierarchical summary ROC model to estimate and compare test accuracy. We used FISH and PCR-based LOH as alternate reference standards to examine how tests compared with those in common use, and conducted a latent class analysis comparing FISH and PCR-based LOH. We constructed an economic model to evaluate cost-effectiveness.
MAIN RESULTS
We included 53 studies examining: PCR-based LOH, FISH, single nucleotide polymorphism (SNP) array, next-generation sequencing (NGS), comparative genomic hybridisation (CGH), array comparative genomic hybridisation (aCGH), multiplex-ligation-dependent probe amplification (MLPA), real-time PCR, chromogenic in situ hybridisation (CISH), mass spectrometry (MS), restriction fragment length polymorphism (RFLP) analysis, G-banding, methylation array and NanoString. Risk of bias was low for only one study; most gave us concerns about how patients were selected or about missing data. We had applicability concerns about many of the studies because only patients with specific subtypes of glioma were included. 1520 participants contributed to analyses using FISH as the reference, 1304 participants to analyses involving PCR-based LOH as the reference and 262 participants to analyses of comparisons between methods from studies not including FISH or PCR-based LOH. Most evidence was available for comparison of FISH with PCR-based LOH (15 studies, 915 participants): PCR-based LOH detected 94% of FISH-determined codeletions (95% credible interval (CrI) 83% to 98%) and FISH detected 91% of codeletions determined by PCR-based LOH (CrI 78% to 97%). Of tumours determined not to have a deletion by FISH, 94% (CrI 87% to 98%) had a deletion detected by PCR-based LOH, and of those determined not to have a deletion by PCR-based LOH, 96% (CrI 90% to 99%) had a deletion detected by FISH. The latent class analysis suggested that PCR-based LOH may be slightly more accurate than FISH. Most other techniques appeared to have high sensitivity (i.e. produced few false-negative results) for detection of 1p/19q codeletion when either FISH or PCR-based LOH was considered as the reference standard, although there was limited evidence. There was some indication of differences in specificity (false-positive rate) with some techniques. Both NGS and SNP array had high specificity when considered against FISH as the reference standard (NGS: 6 studies, 243 participants; SNP: 6 studies, 111 participants), although we rated certainty in the evidence as low or very low. NGS and SNP array also had high specificity when PCR-based LOH was considered the reference standard, although with much more uncertainty as these results were based on fewer studies (just one study with 49 participants for NGS and two studies with 33 participants for SNP array). G-banding had low sensitivity and specificity when PCR-based LOH was the reference standard. Although MS had very high sensitivity and specificity when both FISH and PCR-based LOH were considered the reference standard, these results were based on only one study with a small number of participants. Real-time PCR also showed high specificity with FISH as a reference standard, although there were only two studies including 40 participants. We found no relevant economic evaluations. Our economic model using FISH as the reference standard suggested that the resource-optimising test depends on which measure of diagnostic accuracy is most important. With FISH as the reference standard, MLPA is likely to be cost-effective if society was willing to pay GBP 1000 or less for a true positive detected. However, as the value placed on a true positive increased, CISH was most cost-effective. Findings differed when the outcome measure changed to either true negative detected or correct diagnosis. When PCR-based LOH was used as the reference standard, MLPA was likely to be cost-effective for all measures of diagnostic accuracy at lower threshold values for willingness to pay. However, as the threshold values increased, none of the tests were clearly more likely to be considered cost-effective.
AUTHORS' CONCLUSIONS
In our review, most techniques (except G-banding) appeared to have good sensitivity (few false negatives) for detection of 1p/19q codeletions in glioma against both FISH and PCR-based LOH as a reference standard. However, we judged the certainty of the evidence low or very low for all the tests. There are possible differences in specificity, with both NGS and SNP array having high specificity (fewer false positives) for 1p/19q codeletion when considered against FISH as the reference standard. The economic analysis should be interpreted with caution due to the small number of studies.
Topics: Brain Neoplasms; Chromosomes, Human, Pair 1; Cost-Benefit Analysis; Cross-Sectional Studies; DNA; Diagnostic Tests, Routine; Glioma; Humans; Oligodendroglioma; State Medicine
PubMed: 35233774
DOI: 10.1002/14651858.CD013387.pub2