2.Mcl-1 as a potential therapeutic target for human hepatocelluar carcinoma.
Qin YU ; Zhao-Yu LIU ; Qiong CHEN ; Ju-Sheng LIN
Journal of Huazhong University of Science and Technology (Medical Sciences) 2016;36(4):494-500
Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality in part due to its high resistance to chemotherapeutic drugs. The anti-apoptotic Mcl-1 expression has been reported as a resistance factor in various types of tumors. Here, we investigated the expression of Mcl-1 in hepatoma cells and HCC tissues and its relationship with p53, and analyzed the possibility of the gene as a molecular target for HCC therapy. HCC specimens of 30 patients were examined by immunohistochemistry for Mcl-1 and p53 expression. Mcl-1 expression in hepatoma cell lines was measured by RT-PCR and Western blotting. The suppression of Mcl-1 by RNA interference or specific phosphatidylinositol-3 kinase (PI3K) inhibitor, LY294002, was evaluated as monotherapy, and it was combined with mitomycin C (MMC) in treating hepatoma cell line HepG2. Cell viability and apoptosis were assessed by MTT and FACS analysis. Finally, changes of Mcl-1 or p53 expression in various hepatoma cell lines were examined after transfection with Mcl-1 siRNA, the Mcl-1 expression plasmid, or the wide-type p53 expression plasmid, respectively. Mcl-1 protein was remarkably enhanced in HCC tissues as compared with adjacent non-tumor liver tissues. In addition, Mcl-1 was prominently expressed in HepG2 and Hep3B cells, weakly in SMMC7721 cells, and not in L02 cells. P53 protein was also overexpressed in HCC tissues and there was a significant correlation between the expression of p53 and Mcl-1. Silencing Mcl-1 by RNAi or LY294002 downregulated Mcl-1 expression and led to decreased cell viability and increased apoptosis. Combination of MMC and Mcl-1 RNAi or LY294002 exhibited a significant chemosensitizing effect. The expression of p53 was not influenced by Mcl-1 siRNA in HepG2 cells or transfection with the Mcl-1 expression plasmid in L02 cells. Furthermore, the expression of Mcl-1 in Hep3B cells was also not significantly changed after transfection with the wild-type p53 expression plasmid. It is concluded that Mcl-1 is overexpressed in HCC tissues. The mechanisms by which silencing Mcl-1 sensitizes hepatoma cells towards chemotherapy may be not attributed to the upregulated expression of p53 but the dysfunction of p53 through Mcl-1/p53 interaction. Mcl-1 may be a potential target of gene therapy for HCC.
Adenoma, Liver Cell
;
drug therapy
;
genetics
;
pathology
;
Apoptosis
;
drug effects
;
Biomarkers, Tumor
;
biosynthesis
;
genetics
;
Chromones
;
administration & dosage
;
Gene Expression Regulation, Neoplastic
;
drug effects
;
Hep G2 Cells
;
Humans
;
Liver Neoplasms
;
drug therapy
;
genetics
;
pathology
;
Morpholines
;
administration & dosage
;
Myeloid Cell Leukemia Sequence 1 Protein
;
biosynthesis
;
genetics
;
RNA, Small Interfering
;
genetics
;
Transfection
;
Tumor Suppressor Protein p53
;
biosynthesis
;
genetics
3.Change in Somatostatinergic Tone of Acromegalic Patients according to the Size of Growth Hormone-Producing Pituitary Tumors.
Sang Ouk CHIN ; Suk CHON ; You Cheol HWANG ; In Kyung JEONG ; Seungjoon OH ; Sung Woon KIM
Journal of Korean Medical Science 2013;28(12):1774-1780
The aim of this study was to investigate the relationship between somatostatinergic tone (SST) and the size of growth hormone (GH)-producing pituitary tumors. GH levels of 29 patients with newly diagnosed acromegaly were measured using a 75-gram oral glucose tolerance test (OGTT), an insulin tolerance test (ITT), and an octreotide suppression test (OST). Differences between GH levels during the ITT and the OGTT (DeltaGH(IO)), and between the OGTT and the OST at the same time point (DeltaGH(OS)) were compared according to the size of the tumor and the response pattern to the OST. DeltaGH(IO) of macroadenomas (n=22) was non-significantly higher than those of microadenomas while DeltaGH(OS) of macroadenomas were significantly higher than those of microadenomas. According to further analyses of macroadenomas based on the response pattern to the OST, GH levels during the ITT were significantly higher in non-responders. DeltaGH(OS) showed near-significant differences between responders and non-responders. In conclusion, as the size of the pituitary tumor increases, the effect of glucose on SST appears to be attenuated. Macroadenomas that are non-responders to the OST possess a portion of GH secretion exceeding the range of regulation by SST.
Acromegaly/*diagnosis/*pathology
;
Adenoma/drug therapy/*pathology
;
Adult
;
Aged
;
Antineoplastic Agents, Hormonal/therapeutic use
;
Female
;
Glucose Tolerance Test
;
Human Growth Hormone/*blood/secretion
;
Humans
;
Insulin/blood
;
Insulin-Like Growth Factor I/analysis
;
Male
;
Middle Aged
;
Octreotide/therapeutic use
;
Pituitary Neoplasms/drug therapy/*pathology
4.Korean Guidelines for Colonoscopic Polypectomy.
Suck Ho LEE ; Sung Jae SHIN ; Dong Il PARK ; Seong Eun KIM ; Sung Pil HONG ; Sung Noh HONG ; Dong Hoon YANG ; Bo In LEE ; Young Ho KIM ; Hyun Soo KIM ; Suk Kyun YANG ; Hyo Jong KIM ; Se Hyung KIM ; Hyun Jung KIM
The Korean Journal of Gastroenterology 2012;59(2):85-98
There are indirect evidences to suggest that 80% of colorectal cancers (CRC) develop from adenomatous polyps and that, on average, it takes 10 years for a small polyp to transform into invasive CRC. In multiple cohort studies, colonoscopic polypectomy has been shown to significantly reduce the expected incidence of CRC by 76% to 90%. Colonoscopic polypectomy is performed frequently in primary, secondary and tertiary and medical centers in Korea. However, there are no evidence-based, procedural guidelines for the appropriate performance of this procedure, including the technical aspects. For the guideline presented here, Pubmed, Medline, and Cochrane Library literature searches were performed. When little or no data from well-designed prospective trials were available, an emphasis was placed on the results from large series and reports from recognized experts. Thus, these guidelines for colonoscopic polypectomy are based on a critical review of the available data as well as expert consensus. Further controlled clinical studies are needed to clarify aspects of this statement, and revision may be necessary as new data become available. This guideline is intended to be an educational device to provide information that may assist endoscopists in providing care to patients. This guideline is not a rule and should not be construed as a legal standard of care or as encouraging, advocating, requiring, or discouraging any particular treatment. Clinical decisions for any particular case involve a complex analysis of the patient's condition and the available courses of action.
Adenoma/diagnosis/*surgery
;
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
;
Aspirin/therapeutic use
;
Colonic Polyps/pathology/*surgery
;
Colonoscopy
;
Colorectal Neoplasms/diagnosis/*surgery
;
Databases, Factual
;
Epinephrine/therapeutic use
;
Gastrointestinal Hemorrhage/prevention & control
;
Humans
;
Lymphatic Metastasis
;
Republic of Korea
;
Surgical Instruments
;
Thrombosis/drug therapy
;
Vasoconstrictor Agents/therapeutic use
5.Management of a patient with schizophrenia and underlying pituitary macroadenoma.
Kah Wee NG ; Jimmy LEE ; Verma SWAPNA
Annals of the Academy of Medicine, Singapore 2010;39(11):868-869
Adenoma
;
complications
;
pathology
;
Adult
;
Antipsychotic Agents
;
adverse effects
;
therapeutic use
;
Aripiprazole
;
Benzodiazepines
;
adverse effects
;
therapeutic use
;
Bromocriptine
;
adverse effects
;
therapeutic use
;
Dopamine Antagonists
;
adverse effects
;
therapeutic use
;
Female
;
Hormone Antagonists
;
adverse effects
;
therapeutic use
;
Humans
;
Hyperprolactinemia
;
complications
;
etiology
;
Piperazines
;
adverse effects
;
therapeutic use
;
Pituitary Neoplasms
;
complications
;
pathology
;
Quinolones
;
adverse effects
;
therapeutic use
;
Risperidone
;
adverse effects
;
therapeutic use
;
Schizophrenia
;
drug therapy
;
etiology
;
pathology
;
Serotonin Antagonists
;
adverse effects
;
therapeutic use
;
Trifluoperazine
;
adverse effects
;
therapeutic use