Dalybeach1442
t TAMs in colorectal cancer have protective role for the patient and interfere with primary tumor growth and metastasis. The accumulated data are essential for using TAMs as biomarkers and therapeutic targets to develop cancer-specific immunotherapy and to design efficient combinations of traditional therapy and new immunomodulatory approaches.
The majority of desmoid-type fibromatosis (DTF) tumors harbor a β-catenin mutation, affecting specific codons in
exon 3. S45F tumors are reported to have a higher chance of recurrence after surgery and more resistance to systemic treatments compared to wild-type (WT) and T41A tumors. MMRi62 order of this pilot study was to examine the genome-wide DNA methylation profiles of S45F and T41A mutated DTF, to explain the observed differences in clinical behavior between these DTF subtypes.
Genome-wide analysis of DNA methylation was performed using MeD-seq on formalin-fixed, paraffin-embedded primary DTF samples harboring a S45F (n = 14) or a T41A (n = 15) mutation. Differentially methylated regions (DMRs) between S45F and T41A DTF were identified and used for a supervised hierarchical cluster analysis. DMRs with a fold-change ≥1.5 were considered to be differentially methylated and differences between S45F and T41A tumors were quantitatively assessed. The effect of DMRs on the expression of associated genes was differences in DNA methylation patterns. This implies that distinct DNA methylation profiles are not the sole determinant for the divergent clinical behavior of these different DTF mutant subtypes.
This study demonstrated that S45F and T41A DTF tumors did not exhibit gross differences in DNA methylation patterns. This implies that distinct DNA methylation profiles are not the sole determinant for the divergent clinical behavior of these different DTF mutant subtypes.Non-small cell lung cancer (NSCLC) is the predominant subtype of lung cancers. KRAS mutation is the second most prevalent mutation in NSCLC. KRAS mutant cancer cells suppress the anti-tumor T cell response. However, the underlying mechanism is still unknown. Here, we analyzed the differential expression of acetyl-CoA acyltransferase 1 (ACAA1) in various types of cancers using the TIMER database and validated the results in the NSCLC cell line H1944. We silenced oncogenic KRAS by siRNA targeting KRASG13D, and employed an MAPK signaling pathway inhibitor to clarify the possible regulatory pathway. Moreover, we analyzed the correlation of ACAA1 expression level with B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells. Correlations between expression of ACAA1 and several biomarkers of mutation burden were also tested. Finally, we evaluated the prognostic value of ACAA1 in a wide range of cancers using the Kaplan-Meier Plotter Database. We found lower expression of ACAA1 in tumor tisres further investigation.
Mutation-caused loss-of-function of factors involved in DNA damage response (DDR) is responsible for the development and progression of ~20% of prostate cancer (PCa). Some mutations can be used in cancer risk assessment and informed treatment decisions.
Target capture-based deep sequencing of 11 genes was conducted with total DNA purified from the proband's peripheral blood. Sanger sequencing was conducted to screen potential germline mutations in the proband's family members. Targeted sequencing of a panel of 1,021 genes was done with DNA purified from the tumor tissue.
Two previously unreported germline mutations in the DDR pathway,
(c.8474_8487delCATACCCTATACAG, p.A2825Vfs*15) and
(c.472delC, p.Q158Rfs*19) were identified in a patient with metastatic PCa. A specific therapeutic regimen including androgen deprivation therapy, locally radical radiotherapy, and systemic platinum chemotherapy worked well against his cancer. In addition, the metastatic ovarian cancer in the proband's half-sister harboring the same
germline mutation also responded well to platinum chemotherapy.
The newly identified germline mutations in DDR plays important role in PCa development. Since specific regimen worked well against this cancer, screening of DDR mutation could provide better management for patients with these mutation-mediated PCa.
The newly identified germline mutations in DDR plays important role in PCa development. Since specific regimen worked well against this cancer, screening of DDR mutation could provide better management for patients with these mutation-mediated PCa.
To investigate an implementation method and the results of an inverse dose optimization algorithm, Gradient Based Planning Optimization (GBPO), for three-dimensional brachytherapy.
The GBPO used a quadratic objective function, and a dwell time modulation item was added to the objective function to restrict the dwell time variance. We retrospectively studied 4 cervical cancer patients using different applicators and 15 cervical cancer patients using the Fletcher applicator. We assessed the plan quality of GBPO by isodose lines for the patients using different applicators. For the 15 patients using the Fletcher applicator, we utilized dose-volume histogram (DVH) parameters of HR-CTV (D
, V
) and organs at risk (OARs) (D
, D
, D
) to evaluate the difference between the GBPO plans and the IPSA (Inverse Planning Simulated Annealing) plans, as well as the GBPO plans and the Graphic plans.
For the 4 patients using different applicators, the dose distributions are conformable. For the 15 patients using thento a three-dimensional brachytherapy treatment planning system after studying more sites.Immune checkpoint inhibitors (ICIs) have shown potential to improve the prognosis of patients with brain metastasis (BM) caused by advanced cancers. However, controversies still exist in regard to its survival benefits. In the present work, a time series-based meta-analysis based on the phase I/II/III trials and observational studies were performed to investigate the differences in mortality of ICI-treated BM patients. #link# A number of public library databases, including MEDLINE, EMBASE, OVID, and COCHRANE, were systemically searched by March 2019. The quality of included studies was evaluated by the Newcastle-Ottawa Scale (NOS) scoring. Outcome measures here established were mortality and progression-free survival (PFS) at different follow-up endpoints. Survival rates and curve data were pooled for further analysis. To detect the data heterogeneity, subgroup analyses were conducted according to tumor and ICI types. Eighteen studies, 6 trials, and 12 controlled cohorts were assessed, involving a total of 1330 ICI-treated BM patients.