Variations of the circle of Willis (CW) influence blood supply to the brain and adjacent structures in adults. We examined the formation of the CW in 20 human embryo samples at the end of the embryonic period using 3-D reconstructions of serial histological sections. The CW was closed in all samples, and did not form in a single plane, but was composed of multiple stair-like planes. The artery acutely curved at the caudal part of the CW, namely, at the inlet of the basilar artery and bifurcation of the P1 segment of the posterior cerebral artery (PCA), reflecting flexure of the mesencephalon and diencephalon at this stage. Variations were observed in 17 of 20 samples-only anterior parts (anterior communicating artery [Acom] and anterior cerebral artery [ACA]) in 10 samples, only posterior parts (posterior communicating artery [Pcom]) in one sample, and both anterior and posterior parts in six samples. Variations included the Acom formed as partially duplicated in three samples, duplicated in four, plexiform in three, and no channel as a result of a single azygos ACA in one. The ACA formed as duplicated in two, median ACA in two, and right hypoplasia in one. The Pcom formed in hypoplasia of either side in six samples. Variations observed in this study are similar to those observed in fetuses, neonates, and adults. The P1 segment of PCA was very large in all samples. The present observations indicate that variations in the CW are present from the initiation of CW formation. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc.
Horseshoe lung is a rare pulmonary anomaly characterized by fusion of the posterobasal portions of the right and left lungs behind the pericardial reflection, anterior to the aorta. The majority of reported cases occur in conjunction with scimitar syndrome, including hypoplasia of the right lung, anomalous right pulmonary venous return and systemic arterial supply to the lung. Horseshoe lung is usually diagnosed on pulmonary arteriography when the right inferior pulmonary artery crosses the midline and extends to the left lung base. Bronchography is also diagnostic when the branch of horseshoe portion arises from the right bronchus and passes within the lung parenchyma to midline of the lung tissue. The only described CT finding of horseshoe lung is the contiguity of the right and left lungs behind the heart. Most cases are infants under 12 months of age and CT images are severely hampered by respiration motion artefacts. Such artefacts are minimized by using electron-beam computed tomography, allowing a more detailed CT appearance of horseshoe lung in this case.
Malignant rhabdoid tumor (MRT) is a rare and highly aggressive pediatric malignancy primarily affecting infants and young children. Intensive multimodal therapies currently given to MRT patients are not sufficiently potent to control this highly malignant tumor. Therefore, additive or alternative therapy for these patients with a poor prognosis is necessary. We herein demonstrated that the inhibition of runt-related transcription factor 1 (RUNX1) by novel alkylating conjugated pyrrole-imidazole (PI) polyamides, which specifically recognize and bind to RUNX-binding DNA sequences, was highly effective in the treatment of rhabdoid tumor cell lines in vitro as well as in an in vivo mouse model. Therefore, suppression of RUNX1 activity may be a novel strategy for MRT therapy. K E Y W O R D S malignant rhabdoid tumor, p53, polyamide, RUNX1 1 BACKGROUND Malignant rhabdoid tumor (MRT) is a rare and highly aggressive malignancy, which affects infants and young children. 1 MRT occurs at various anatomical locations including the kidneys, central nervous system (CNS), liver, heart, mediastinum, uterus, adnexa, urinary blad-Abbreviations: Chb-M′, chlorambucil-M prime; MRT, malignant rhabdoid tumor der, and soft tissue. Despite the existing standard intensive multimodal therapy, the long-term survival rate of MRT patients is less than 30%. 2,3 Therefore, more effective treatments are highly desired. The genetic hallmark of rhabdoid tumors are mutations of SMARCB1 (INI1), a core subunit of the SWI/SNF chromatin-remodeling complex. SMARCB1 has potent tumor suppressor activity, and Wang et al reported that oncogenesis caused by loss of SMARCB1 might be dependent on the activity of the residual SWI/SNF
Patients with refractory graft‐versus‐host disease (GVHD) have a dismal prognosis. Therefore, novel therapeutic targets are still needed to be identified. Runt‐related transcriptional factor (RUNX) family transcription factors are essential transcription factors that mediate the essential roles in effector T cells. However, whether RUNX targeting can suppress, and GVHD is yet unknown. Here, we showed that RUNX family members have a redundant role in directly transactivating NFATC2 expression in T cells. We also found that our novel RUNX inhibitor, Chb‐M’, which is the inhibitor that switches off the entire RUNX family by alkylating agent–conjugated pyrrole‐imidazole (PI) polyamides, inhibited T‐cell receptor mediated T cell proliferation and allogenic T cell response. These were designed to specifically bind to consensus RUNX‐binding sequences (TGTGGT). Chb‐M’ also suppressed the expression of NFATC2 and pro‐inflammatory cytokine genes in vitro. Using xenogeneic GVHD model, mice injected by Chb‐M’ showed almost no sign of GVHD. Especially, the CD4 T cell was decreased and GVHD‐associated cytokines including tissue necrosis factor‐α and granulocyte‐macrophage colony‐stimulating factor were reduced in the peripheral blood of Chb‐M’ injected mice. Taken together, our data demonstrates that RUNX family transcriptionally upregulates NFATC2 in T cells, and RUNX‐NFATC2 axis can be a novel therapeutic target against GVHD.
Malignant rhabdoid tumor (MRT) is a highly aggressive pediatric malignancy with no effective therapy. Therefore, it is necessary to identify a target for the development of novel molecule-targeting therapeutic agents. In this study, we report the importance of the runt-related transcription factor 1 (RUNX1) and RUNX1-Baculoviral IAP (inhibitor of apoptosis) Repeat-Containing 5 (BIRC5/survivin) axis in the proliferation of MRT cells, as it can be used as an ideal target for anti-tumor strategies. The mechanism of this reaction can be explained by the interaction of RUNX1 with the RUNX1binding DNA sequence located in the survivin promoter and its positive regulation. Specific knockdown of RUNX1 led to decreased expression of survivin, which subsequently suppressed the proliferation of MRT cells in vitro and in vivo. We also found that our novel RUNX inhibitor, Chb-M, which switches off RUNX1 using alkylating agent-conjugated pyrrole-imidazole polyamides designed to specifically bind to consensus RUNX-binding sequences (5′-TGTGGT-3′), inhibited survivin expression in vivo. Taken together, we identified a novel interaction between RUNX1 and survivin in MRT. Therefore the negative regulation of RUNX1 activity may be a novel strategy for MRT treatment.
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