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The chromosome translocation t(8;19)(p11;q13) has been reported in only six acute myeloid leukemia (AML) patients. We here present the genetic and clinical features of the seventh AML case with this aberration.
Cytogenetic and molecular genetic investigations were performed on leukemic bone marrow cells from a patient with therapy-related AML.
A t(8;19)(p11;q13) was found leading to an in-frame fusion of exon 16 of the lysine acetyltransferase 6A gene (KAT6A) from 8p11 with exon 2 of the leucine twenty homeobox gene (LEUTX) from 19q13 resulting in expression of the otherwise silent LEUTX gene in the leukemic cells. The KAT6A-LEUTX protein is predicted to act as a histone acetyltransferase at its amino-terminal-KAT6A moiety but as a homeobox transcription factor at the LEUTX-carboxyl-terminal moiety.
The present case is the second therapy-related AML, and the third AML overall, in which both a t(8;19)(p11;q13) and its molecular result, a KAT6A-LEUTX fusion gene, are described. The t(8;19)(p11;q13)/KAT6A-LEUTX deregulates transcription and induces leukemogenesis.
The present case is the second therapy-related AML, and the third AML overall, in which both a t(8;19)(p11;q13) and its molecular result, a KAT6A-LEUTX fusion gene, are described. The t(8;19)(p11;q13)/KAT6A-LEUTX deregulates transcription and induces leukemogenesis.
Osteosarcoma is the most frequent malignant bone tumor. OSS_128167 Failure of first-line therapy results in poor prognosis of osteosarcoma. In the present report, we examined the efficacy of the combination of oral recombinant methioninase (o-rMETase) and docetaxel (DOC) on an osteosarcoma patient-derived orthotopic xenograft (PDOX) mouse model.
Osteosarcoma-PDOX models were established by tumor insertion within the tibia of nude mice. The osteosarcoma PDOX models were randomized into four groups (4-5 mice per group) control; o-rMETae alone; DOC alone; o- rMETase combined with DOC. The treatment period was 3 weeks.
The combination of o-rMETase and DOC showed significant efficacy compared to the control group (p=0.03). In contrast, there was no significant efficacy of o-rMETase alone or DOC alone (p=0.65, 0.60, respectively).
o-rMETase converted an osteosarcoma PDOX from DOC-resistant to -sensitive. This combination therapy may be effective against recalcitrant osteosarcoma and other recalcitrant cancers.
o-rMETase converted an osteosarcoma PDOX from DOC-resistant to -sensitive. This combination therapy may be effective against recalcitrant osteosarcoma and other recalcitrant cancers.
We sought to identify the mechanisms of perineural invasion in pancreatic ductal adenocarcinoma (PDAC).
We utilized in vitro cancer cell-nerve co-culture models comprising human PDAC cell lines (MIA Paca2 and PANC-1) and a dorsal root ganglion (DRG) isolated from neonatal mice. We compared gene expression profiles between cell lines with/without DRG conditioned medium (DRG-CM) using RNA-sequencing (RNA-seq).
Migration, invasion, and neurotropism were significantly enhanced in MIA Paca2 but not in PANC-1 cells co-cultured with DRGs. Among 285 genes which showed significant differences in expression levels between cell lines in RNA-seq, we focused on Ephrin receptor A4 (EPHA4), which was upregulated in MIA Paca2 cells treated with DRG-CM. The abilities of migration, invasion, and neurotropism enhanced by DRG co-culture were abolished when EPHA4 was knocked down by siRNA in MIA Paca2 cells.
EPHA4 can be a potential target gene to regulate perineural invasion in PDAC cells.
EPHA4 can be a potential target gene to regulate perineural invasion in PDAC cells.The standard treatment for gastrointestinal cancer is surgical resection and perioperative adjuvant treatment. Multidisciplinary treatment for gastrointestinal cancer leads to body composition changes. Body composition changes, such as skeletal muscle loss and body weight loss, during multidisciplinary treatment result in poor physical activity, severe toxicity of chemotherapy and/or radiation therapy, and poor oncological outcomes. Therefore, the hypothesis is that minimization of body composition changes during multidisciplinary treatment in gastrointestinal cancer patients, the continuation of postoperative adjuvant treatment in these patients might improve, thereby improving the oncological outcomes. Given this hypothesis, recent studies have focused on introducing perioperative oral nutritional treatment for gastrointestinal cancer patients. Thus far, oral nutritional treatment has proven promising and showed some clinical benefits for gastrointestinal cancer patients during the perioperative period. However, whether or not oral nutritional treatment has clinical benefits on the long-term oncological outcomes in gastrointestinal cancer remains unclear. To optimize oral nutritional treatment for gastrointestinal cancer patients, it is necessary to clarify the benefits of oral nutritional treatment on the long-term oncological outcomes in gastric cancer patients and establish the optimal approach to oral nutritional treatment.Medulloblastoma (MB) is the most frequent malignant brain tumor in children. Treatment of MB is based on histopathological and molecular stratification, and includes surgical intervention, often with craniospinal irradiation and adjuvant chemotherapy. Unfortunately, however, this treatment leads to a high morbidity rate, and it does not cure all patients either, with around 30% succumbing to their disease. With improved cancer genomics and better molecular characterization, MB has been classified into four major subgroups, wingless-activated, sonic hedgehog-activated, Group 3, and Group 4, with each group consisting of additional subtypes. Recently disclosed genetic drivers of MB may in the future help improve treatment, and in this way reduce therapy-related toxicity. In this review, we describe the heterogeneity of the MB subgroups, and potential new options for targeted therapy.
To describe the proportion of children with an index hospitalization in 2014 who had established long-term invasive ventilator dependence (LTVD), and determine regional variation in hospital length of stay, charges, and readmissions.
Multicenter, longitudinal, retrospective cohort study using a recently established algorithm to identify children with LTVD from the Pediatric Health Information System database with an index hospitalization at least once during 2014, excluding normal newborn care or chemotherapy, and the subset with established LTVD. Hospitals were grouped by geographic regions. Analysis included descriptive statistics and multi-variable mixed modeling for length of stay, charges, and readmissions.
Of the 615,883 unique children discharged from 45 children's hospitals in 2014, 2235 (0.4%) had established LTVD. Of these, 342 (15%) were hospitalized in the Northeast, 677 (30%) Midwest, 733 (32%) South and 481 (22%) West. Most had at least two complex chronic conditions (97%) and used a medical device for at least two body systems (71%).