Imerslund-Gräsbeck syndrome in a child with a novel compound heterozygous mutations in the AMN gene: a case report.

Background: Imerslund-Gräsbeck syndrome (IGS) is an autosomal recessive disorder characterized by selective vitamin B12 malabsorption, resulting in vitamin B12 deficiency and impaired reabsorption of proximal tubular proteins.This case highlights a previously unidentified compound heterozygous variant in the Amnionless (AMN) gene that causes IGS syndrome and underscores the importance of long-term oral vitamin B12 replacement therapy in managing the condition.

Case Presentation: In this retrospective analysis, we present the clinical data of a 3-year and 6-month-old female child diagnosed with IGS at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China, in November 2018.

Case report: Genetic analysis of a novel intronic inversion variant in the gene associated with hereditary spherocytosis.

Hereditary spherocytosis (HS) is a congenital haemolytic anaemia attributed to dysregulation or abnormal quantities of erythrocyte membrane proteins. Currently, the most common erythrocytic gene, spectrin β (), variants are located in exons and give rise to mRNA defects. However, the genetic characteristics and pathogenic mechanisms of intronic variants are not completely understood.

W-Compound can be used as a Biomarker for Fetal Thyroid Function and a Potential Tool for Screening Congenital Hypothyroidism.

Sulfoconjugation is the major pathway for thyroid hormone (TH) metabolism, converting T4 to inactive metabolites, T4S, rT3S, and T3S in fetus, via sulfotransferases (SULT) and type 3 deiodinase in gestation. Consistent with high production rate of T4S and rT3S, there are high serum sulfated iodothyronine analogs, including T4S, T3S, rT3S, and 3,3'-T2S (T2S), in ovine and human fetal and preterm infants. Fetal TH metabolic pathways predict T2S as the major TH metabolite in the fetus.

Case Report: Is Surgical Treatment Beneficial for Intracranial Basal Ganglia Cunninghamellamycosis Following Haematopoietic Stem Cell Transplantation?

Cunninghamellamycosis is an unusual but often highly fatal mucormycosis caused by , which belongs to the basal lineage order Mucorales. It is especially fatal when the central nervous system is involved. So far, there are few reported cases of surgical treatment for intracranial mucormycosis in children after allogeneic haematopoietic stem cell transplantation (HSCT).

Mechanisms of Senescence-Related NKG2D Ligands Release and Immune Escape Induced by Chemotherapy in Neuroblastoma Cells.

Chemotherapy-induced senescence promotes immunocyte aggregation in the tumor microenvironment by upregulating the surface expression of activating ligands in cancer cells. However, these senescent tumor cells cannot be completely cleared and can induce tumor recurrence. Previous studiesshowed that soluble natural killer (NK) group 2D (NKG2D) ligands impair the recognition of multiple immune cells.

Successful low-dose chemotherapy for refractory Epstein-Barr virus-related post-transplant lymphoproliferative disorder following hematopoietic stem cell transplantation in a child with Wiskott-Aldrich syndrome.

We report the first case of a 12-year-old boy with Wiskott-Aldrich syndrome who developed CD20-weakly expressed and CD30-highly expressed Epstein-Barr virus-related post-transplant lymphoproliferative disorder refractory to rituximab treatment. The patient was effectively and safely treated with personalized low-dose chemotherapy and subsequently remained in complete remission for 1 year.

C/EBPβ enhances platinum resistance of ovarian cancer cells by reprogramming H3K79 methylation.

Chemoresistance is a major unmet clinical obstacle in ovarian cancer treatment. Epigenetics plays a pivotal role in regulating the malignant phenotype, and has the potential in developing therapeutically valuable targets that improve the dismal outcome of this disease. Here we show that a series of transcription factors, including C/EBPβ, GCM1, and GATA1, could act as potential modulators of histone methylation in tumor cells.

Prognostic and therapeutic value of disruptor of telomeric silencing-1-like (DOT1L) expression in patients with ovarian cancer.

Background: Epigenetics has been known to play a critical role in regulating the malignant phenotype. This study was designed to examine the expression of DOT1L (histone 3 lysine 79 methyltransferase) and H3K79 methylation in normal ovarian tissues and ovarian tumors and to explore the function of DOT1L and its underline mechanisms in ovarian cancer.

Methods: The expression of DOT1L and H3K79 methylation in 250 ovarian tumor samples and 24 normal ovarian samples was assessed by immunohistochemistry.

SIX1 coordinates with TGFβ signals to induce epithelial-mesenchymal transition in cervical cancer.

Epithelial-mesenchymal transition (EMT) plays a critical role in promoting tumor invasion and metastasis. However, the key cofactors that modulate the signal transduction to induce EMT have note been fully explored to date. The present study reports that sine oculis homeobox homolog 1 (SIX1) is able to promote EMT of cervical cancer by coordinating with transforming growth factor (TGF)β-SMAD signals.

Pharmacodynamics (PD) and pharmacokinetics (PK) of E7389 (eribulin, halichondrin B analog) during a phase I trial in patients with advanced solid tumors: a California Cancer Consortium trial.

Background: The California Cancer Consortium completed a phase I trial of E7389 (eribulin mesylate), an analog of the marine natural product halichondrin B. This trial was to determine the pharmacodynamics, pharmacokinetics, and MTD of E7389 administered by bolus injection weekly for 3 weeks out of four.

Methods: This trial included a rapid titration design.

SIX1 promotes tumor lymphangiogenesis by coordinating TGFβ signals that increase expression of VEGF-C.

Lymphatic vessels are one of the major routes for the dissemination of cancer cells. Malignant tumors release growth factors such as VEGF-C to induce lymphangiogenesis, thereby promoting lymph node metastasis. Here, we report that sine oculis homeobox homolog 1 (SIX1), expressed in tumor cells, can promote tumor lymphangiogenesis and lymph node metastasis by coordinating with TGFβ to increase the expression of VEGF-C.

Sine oculis homeobox homolog 1 promotes DNA replication and cell proliferation in cervical cancer.

Malignant proliferation is the fundamental trait of tumor cells. The initiation of DNA replication represents a key process for cell proliferation, and has a marked impact on tumorigenesis and progression. Here we report that Sine oculis homeobox homolog 1 (SIX1) functions as a master regulator in DNA replication of cervical cancer cells.

Sine oculis homeobox homolog 1 promotes α5β1-mediated invasive migration and metastasis of cervical cancer cells.

Sine oculis homeobox homolog 1 (SIX1) has been supposed to be correlated with the metastasis and poor prognosis of several malignancies. However, the effect of SIX1 on the metastatic phenotype of tumor cells and the underlying mechanisms were still unclear to date. Here we report that SIX1 can promote α5β1-mediated metastatic capability of cervical cancer cells.

Effects of iodonium-class flavin dehydrogenase inhibitors on growth, reactive oxygen production, cell cycle progression, NADPH oxidase 1 levels, and gene expression in human colon cancer cells and xenografts.

Iodonium-class flavoprotein dehydrogenase inhibitors have been demonstrated to possess antiproliferative potential and to inhibit reactive oxygen production in human tumor cells, although the mechanism(s) that explains the relationship between altered cell growth and the generation of reactive oxygen species (ROS) remains an area of active investigation. Because of the ability of these compounds to inhibit the activity of flavoprotein-containing epithelial NADPH oxidases, we chose to examine the effects of several iodonium-class flavoprotein inhibitors on human colon cancer cell lines that express high, functional levels of a single such oxidase (NADPH oxidase 1, or Nox1). We found that diphenyleneiodonium (DPI), di-2-thienyliodonium (DTI), and iodonium diphenyl inhibited the growth of Caco2, HT-29, and LS-174T colon cancer cells at concentrations (10-250nM for DPI, 0.

Phase I study of nelfinavir in liposarcoma.

Purpose: HIV protease inhibitors are associated with HIV protease inhibitor-related lipodystrophy syndrome. We hypothesized that liposarcomas would be similarly susceptible to the apoptotic effects of an HIV protease inhibitor, nelfinavir.

Methods: We conducted a phase I trial of nelfinavir for liposarcomas.

Single-dose pharmacokinetic and toxicity analysis of pyrrole-imidazole polyamides in mice.

Purpose: Pyrrole-imidazole (Py-Im) polyamides are programmable, sequence-specific DNA minor groove-binding ligands. Previous work in cell culture has shown that various polyamides can be used to modulate the transcriptional programs of oncogenic transcription factors. In this study, two hairpin polyamides with demonstrated activity against androgen receptor signaling in cell culture were administered to mice to characterize their pharmacokinetic properties.

Nelfinavir induces liposarcoma apoptosis through inhibition of regulated intramembrane proteolysis of SREBP-1 and ATF6.

Purpose: We previously reported that nelfinavir (NFV) induces G(1) cell-cycle block and apoptosis selectively in liposarcoma cell lines due to increased SREBP-1 (sterol regulatory element binding protein-1) expression in the absence of increased transcription. We postulate that NFV interferes with regulated intramembrane proteolysis of SREBP-1 and ATF6 (activating transcription factor 6).

Experimental Design: Time-lapse, confocal microscopic studies show that NFV inhibits the nuclear translocation of full-length SREBP-1-EGFP and ATF6-EGFP fusion proteins.

Advanced glycation end products of DNA: quantification of N2-(1-Carboxyethyl)-2'-deoxyguanosine in biological samples by liquid chromatography electrospray ionization tandem mass spectrometry.

Methylglyoxal (MG) and related alpha-oxoaldehydes react with proteins, lipids, and DNA to give rise to covalent adducts known as advanced glycation end products (AGEs). Elevated levels of AGEs have been implicated in the pathological complications of diabetes, uremia, Alzheimer's disease, and possibly cancer. There is therefore widespread interest in developing sensitive methods for the in vivo measurement of AGEs as prognostic biomarkers and for treatment monitoring.

Oblimersen and alpha-interferon in metastatic renal cancer: a phase II study of the California Cancer Consortium.

Purpose: Oblimersen is an 18-base oligodeoxynucleotide encoding antisense to the gene for bcl-2, an anti-apoptotic protein that is upregulated in renal and other cancers. This study was designed to evaluate the combination of oblimersen with alpha-Interferon in advanced renal cancer. Trial endpoints were antitumor efficacy and toxicity, pharmacokinetics, and evidence of apoptosis in peripheral blood mononuclear cells.

Phase I trial of intraperitoneal gemcitabine in the treatment of advanced malignancies primarily confined to the peritoneal cavity.

Purpose: To determine the maximally tolerated dose, toxicity, and pharmacokinetics of i.p. gemcitabine.

A dityrosyl-diiron radical cofactor center is essential for human ribonucleotide reductases.

Ribonucleotide reductase catalyzes the reduction of ribonucleotides to deoxyribonucleotides for DNA biosynthesis. A tyrosine residue in the small subunit of class I ribonucleotide reductase harbors a stable radical, which plays a central role in the catalysis process. We have discovered that an additional tyrosine residue, conserved in human small subunits hRRM2 and p53R2, is required for the radical formation and enzyme activity.