ABSTRACT
Cancer immunotherapies are preferred over conventional treatments which are highly cytotoxic to normal cells. Focus has been on T cells but natural killer (NK) cells have equal potential. Concepts in cancer control and influence of sex require further investigation to improve successful mobilization of immune cells in cancer patients. Acute lymphoblastic leukemia (ALL) is a hematological malignancy mainly of B cell (B-ALL) and T cell (T-ALL) subtypes. Influence of ALL on NK cell is still unclear. Targeted next-generation sequencing was conducted on 62 activating/inhibitory receptors, ligands, effector, and exhaustion molecules on T-ALL (6 males) and normal controls (NC) (4 males and 4 females). Quantitative PCR (q-PCR) further investigated copy number variation (CNV), methylation index (MI), and mRNA expression of significant genes in T-ALL (14 males), NC (12 males and 12 females), and B-ALL samples (N = 12 males and 12 females). Bioinformatics revealed unique variants particularly rs2253849 (T>C) in KLRC1 and rs1141715 (A>G) in KLRC2 only among T-ALL (allele frequency 0.8-1.0). Gene amplification was highest in female B-ALL compared to male B-ALL (KLRC2, KLRC4, and NCR3, p < 0.05) and lowest in male T-ALL cumulating in deletion of KLRD1 and CD69. MI was higher in male ALL of both subtypes compared to normal (KIR2DL1-2 and 4 and KIR2DS2 and 4, p < 0.05) as well as to female B-ALL (KIR3DL2 and KIR2DS2, p < 0.05). mRNA expressions were low. Thus, ALL subtypes potentially regulated NK cell suppression by different mechanisms which should be considered in future immunotherapies for ALL.
Subject(s)
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , DNA Copy Number Variations , Female , Humans , Killer Cells, Natural , Male , NK Cell Lectin-Like Receptor Subfamily C/metabolism , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/metabolism , RNA, Messenger/metabolism , Receptors, Natural Killer Cell/genetics , Receptors, Natural Killer Cell/metabolismABSTRACT
CONTEXT: Bauhinia purpurea L. (Fabaceae) is a native plant species of many Asian countries, including Malaysia and India. In India, the root, stem, bark, and leaf of B. purpurea are used to treat various ailments, including ulcers and stomach cancer. OBJECTIVE: In an attempt to establish its pharmacological potential, we studied the antiulcer activity of lipid-soluble extract of B. purpurea obtained via extraction of air-dried leaves using chloroform. MATERIALS AND METHODS: The rats were administered the chloroform extract (dose range of 100-1000 mg/kg) orally after 24 h fasting. They were subjected to the absolute ethanol- and indomethacin-induced gastric ulcer, and pyloric ligation assays after 30 min. The acute toxicity study was conducted using a single oral dose of 5000 mg/kg extract and the rats were observed for the period of 14 days. omeprazole (30 mg/kg) was used as the standard control. RESULTS: At 5000 mg/kg, the extract produced no sign of toxicity in rats. The extract exhibited significant (p < 0.05) dose-dependent antiulcer activity for the ethanol-induced model. The extract also significantly (p < 0.05) increased the gastric wall mucus production and pH of gastric content, while significantly (p < 0.05) reducing the total volume and total acidity of the gastric content in the pylorus ligation assay. DISCUSSION AND CONCLUSION: The extract possesses antiulcer, antisecretory and cytoprotective activities, which could be attributed to its flavonoid and tannin content. These findings provide new information regarding the potential of lipid-soluble compounds of B. purpurea for the prevention and treatment of gastric ulcers.
