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1.
Case Rep Med ; 2021: 6869342, 2021.
Article in English | MEDLINE | ID: mdl-34887925

ABSTRACT

INTRODUCTION: Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy due to an acquired autoantibody to ADAMTS13 that requires a boutique treatment, urgent plasma exchange. Thus, TTP is often termed a "cannot miss" diagnosis. CASE: We report a patient with TTP who had a history of immune thrombocytopenia (ITP), had atypical demographics for TTP, and had also met criteria for primary Sjogren's syndrome. This exceedingly rare combination presented a temptation to dismiss TTP as a diagnosis. Discussion. Our case further demonstrates the practical utility of using the PLASMIC score as a tool that can help identify patients with TTP even when the patient has statistically rare characteristics.

2.
Int J Cancer ; 145(11): 3022-3032, 2019 12 01.
Article in English | MEDLINE | ID: mdl-31018249

ABSTRACT

The normal colon epithelium is transformed into its neoplastic counterpart through a series of genetic alterations in driver genes including activating mutations in PIK3CA. Treatment often involves surgery followed by 5-fluorouracil (5-FU) based therapy, which has limited efficiency and serious side effects. We sought to determine whether fisetin, a dietary flavonoid, alone or in combination with 5-FU affected tumorigenesis in the mammalian intestine. We first determined the effect of fisetin, 5-FU or their combination on PIK3CA-mutant and PIK3CA wild-type colon cancer cells by assessing cell viability, colony formation, apoptosis and effects on PI3K/AKT/mTOR signaling. Treatment of PIK3CA-mutant cells with fisetin and 5-FU reduced the expression of PI3K, phosphorylation of AKT, mTOR, its target proteins, constituents of mTOR signaling complex and this treatment increased the phosphorylation of AMPKα. We then determined whether fisetin and 5-FU together or singly affected tumorigenesis in ApcMin/+ mice that also express constitutively active PI3K in the distal small intestine and colon. Tumor incidence was markedly lower in fisetin-treated FC1 3K1 ApcMin/+ mice that also express constitutively active PI3K in distal small intestine and colon, as compared to control animals, indicating that fisetin is a strong preventive agent. In addition, the combination of fisetin and 5-FU also reduced the total number of intestinal tumors. Fisetin could be used as a preventive agent plus an adjuvant with 5-FU for the treatment of PIK3CA-mutant colorectal cancer.


Subject(s)
Class I Phosphatidylinositol 3-Kinases/genetics , Colorectal Neoplasms/drug therapy , Flavonoids/administration & dosage , Fluorouracil/administration & dosage , Mutation , Animals , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Colorectal Neoplasms/genetics , Drug Synergism , Flavonoids/pharmacology , Flavonols , Fluorouracil/pharmacology , HCT116 Cells , HT29 Cells , Humans , Mice , Phosphorylation/drug effects , Signal Transduction/drug effects , Xenograft Model Antitumor Assays
3.
Anticancer Res ; 36(3): 845-52, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26976970

ABSTRACT

BACKGROUND: Despite receiving post-operative 5-fluorouracil (5-FU)-based chemotherapy, approximately 50% of patients with stage IIIC colon cancer experience recurrence. Currently, no molecular signature can predict response to 5-FU. MATERIALS AND METHODS: Mouse models of colon cancer have been developed and characterized. Individual tumors in these mice can be longitudinally monitored and assessed to identify differences between those that are responsive and those that are resistant to therapy. Gene expression was analyzed in serial biopsies that were collected before and after treatment with 5-FU. Colon tumors had heterogeneous responses to treatment with 5-FU. Microarray analysis of pre-treatment biopsies revealed that Hp1bp3, a gene encoding heterochromatin protein 1 binding protein 3, was differentially expressed between sensitive and resistant tumors. CONCLUSION: Using mouse models of human colorectal cancer, Hp1bp3 was identified as a candidate marker of intrinsic 5-FU resistance and may represent a potential biomarker for patient stratification or a target of clinical importance.


Subject(s)
Biomarkers, Tumor/genetics , Colonic Neoplasms/chemically induced , Colonic Neoplasms/genetics , Drug Resistance, Neoplasm , Nuclear Proteins/genetics , Animals , Colonic Neoplasms/drug therapy , Colonic Neoplasms/pathology , Dextran Sulfate , Female , Fluorouracil/therapeutic use , Gene Expression Profiling , Gene Expression Regulation, Neoplastic/drug effects , Humans , Male , Mice , Oligonucleotide Array Sequence Analysis
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