No abstract available.
Colitis, Ulcerative/*drug therapy ; Female ; Humans ; Janus Kinases/*antagonists & inhibitors ; Male ; Protein Kinase Inhibitors/*administration & dosage ; Pyrimidines/*administration & dosage ; Pyrroles/*administration & dosage

In January 2006, Sunitinib was approved by the US Food and Drug Administration for the treatment of advanced renal cell carcinoma and gastrointestinal stromal tumor. Sunitinib inhibits the receptor tyrosine kinases that are involved with various receptors whose functions are related to tumor growth, angiogenesis and metastatic progression. The cutaneous adverse reactions of hand-foot syndrome associated with sunitinib are well known, but there have been no previous reports on these reactions in the Korean medical literature. We report here on a case of hand-foot syndrome due to this drug, and we discuss the possible mechanism of hand-foot syndrome caused by sunitinib.
Carcinoma, Renal Cell ; Gastrointestinal Stromal Tumors ; Hand-Foot Syndrome ; Indoles ; Paronychia ; Phosphotransferases ; Pyrroles ; Tyrosine ; United States Food and Drug Administration

In January 2006, Sunitinib was approved by the US Food and Drug Administration for the treatment of advanced renal cell carcinoma and gastrointestinal stromal tumor. Sunitinib inhibits the receptor tyrosine kinases that are involved with various receptors whose functions are related to tumor growth, angiogenesis and metastatic progression. The cutaneous adverse reactions of hand-foot syndrome associated with sunitinib are well known, but there have been no previous reports on these reactions in the Korean medical literature. We report here on a case of hand-foot syndrome due to this drug, and we discuss the possible mechanism of hand-foot syndrome caused by sunitinib.
Carcinoma, Renal Cell ; Gastrointestinal Stromal Tumors ; Hand-Foot Syndrome ; Indoles ; Paronychia ; Phosphotransferases ; Pyrroles ; Tyrosine ; United States Food and Drug Administration

OBJECTIVE: To determine the effect of different doses of atorvastatin on the serum soluble intercellular adhesion molecules-1 (sICAM-1) in patients undergoing percutaneous coronary intervention (PCI). METHODS: The study consisted of 38 patients with unstable angina and 10 patients with old infarction who underwent elected PCI for stenotic lesions of the coronary artery. Patients were randomly assigned to either aggressive group or conventional one. After PCI the patients took atorvastatin 20 mg per day or 10 mg per day. Blood lipid profile was examined before, and 3 months after the PCI. SICAM-1 was examined before the PCI, 48 hours and 3 months after the PCI. RESULTS: The total cholesterol and LDL-Cholesterol 3 months after the PCI in the 2 groups were lower than those before the PCI (P<0.01). The aggressive group showed greater reduction in concentrations of TC and LDL-C than the conventional group (P<0.01). The changes in concentrations of HDL-C between pre-PCI and 3 months after the PCI and TG were not obvious (P>0.05). sICAM-1 in the 2 groups 48 hours after the PCI significantly higher than that before the PCI (P<0.01). But sICAM-1 in the 2 groups 3 months after the PCI significantly lower than that before the PCI (P<0.01 or P<0.05). The aggressive group showed greater reduction than the conventional group (P<0.01). TC and LDL-C were positively correlated with sICAM-1(r=0.2413, r=0.2691, all P<0.05). CONCLUSION Atorvastatin 20 mg per day reduces TC, LDL-C, and sICAM-1 to a greater extent than atorvastatin 10 mg per day. The effect on sICAM-1 is partly related to reduce lipid profile.
Aged ; Atorvastatin ; Female ; Heptanoic Acids ; administration & dosage ; therapeutic use ; Humans ; Intercellular Adhesion Molecule-1 ; blood ; Male ; Middle Aged ; Percutaneous Coronary Intervention ; Pyrroles ; administration & dosage ; therapeutic use

OBJECTIVETo investigate the efficacy and safety of sunitinib as first-line therapy for metastatic renal cell carcinoma (mRCC) on a 2 weeks on/1 week off intermittent dosing schedule.

METHODSA total of 11 mRCC patients were enrolled to receive sunitinib 50 mg/day in 2 weeks on/1 week off schedule per 6 weeks till disease progression or intolerable toxicity occurred. The primary end point was progression free survival (PFS), the secondary end points were overall survival (OS), incidence of adverse effects and objective response.

RESULTSThe objective response rate in the 11 cases was 45.5% and disease control rate 72.7% (partial response n = 5, stable disease n = 3). Till the last follow up on Dec 2013, the median PFS was 17.0 months (95% CI 7.3 to 26.7 months), and median OS 26.0 months (95% CI 2.2 to 49.8 months). The common adverse events included leucopenia, thrombocytopenia, diarrhea, mucositis and hand-foot skin reaction. Dose reduction to 37.5 mg was seen only in 2 patients without discontinuation.

CONCLUSIONSSunitinib on an intermittent dosing schedule 2 weeks on /1 week off as first-line therapy for mRCC patients shows a good efficacy and tolerance, with less grade 3-4 drug-related toxicities and a tendency of prolonged PFS in mRCC patients.

Antineoplastic Agents ; administration & dosage ; pharmacology ; therapeutic use ; Carcinoma, Renal Cell ; drug therapy ; Disease-Free Survival ; Drug Administration Schedule ; Humans ; Indoles ; administration & dosage ; pharmacology ; therapeutic use ; Kidney Neoplasms ; drug therapy ; Pilot Projects ; Pyrroles ; administration & dosage ; pharmacology ; therapeutic use ; Treatment Outcome

BACKGROUNDSunitinib has been proved an effective new option for treatment of metastatic renal cell carcinoma (mRCC). Analysis of clinical data of 22 patients, who were exposed to sunitinib for at least 1 year, was conducted to evaluate the long-term efficacy and safety of sunitinib for the treatment of mRCC.

METHODSA total of 54 patients with mRCC were treated with sunitinib malate, 50 mg/d orally, on a 4-weeks-on and 2-weeks-off dosing schedule in Peking University First Hospital. Treatment continued until disease progression, unacceptable adverse events (AEs), or death. Among them, 22 patients continued treatment for at least 1 year. The clinical data of these 22 patients were prospectively collected for analysis. AEs were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0. Tumor response was evaluated in accordance with the Response Evaluation Criteria in Solid Tumors.

RESULTSMedian progression-free survival was 19.5 months until last follow-up. The best efficacy results achieved were complete response, partial response, and stable disease for 2, 9, and 11 patients, respectively. Objective response rate was 50%. The most common AEs were hand-foot syndrome (95%) and hypertension (91%). Other common AEs were thyroid-stimulating hormone elevation (82%), platelet decrease (77%), and loss of appetite (77%). Only one patient withdrew from treatment for cardiac infarction. Another nine patients experienced dose modifications or short-term suspensions.

CONCLUSIONLong-term exposure to sunitinib malate showed encouraging efficacy in the treatment of mRCC. At the same time, the tolerability was good.

Adult ; Aged ; Antineoplastic Agents ; administration & dosage ; Carcinoma, Renal Cell ; drug therapy ; pathology ; Drug Administration Schedule ; Female ; Follow-Up Studies ; Humans ; Indoles ; administration & dosage ; Kidney Neoplasms ; drug therapy ; pathology ; Male ; Middle Aged ; Neoplasm Metastasis ; Pyrroles ; administration & dosage ; Young Adult

OBJECTIVETo evaluate whether taking atorvastatin for long time has positive effects on age-related renal impairment.

METHODS20-month-age normal female Wistar rats were divided into three groups (n = 9). First group were fed atorvastatin 10 mg/(kg x d). Second group were fed atorvastatin 1 mg/(kg x d). Third group were fed the same volume normal saline served as control. All the rats were sacrificed after four months. 3-month-age normal female Wistar rats (n = 9) also served as normal control. Kidney weight, serum creatinine (Scr) and blood-lipoids were measured. Paraffin sections of renal tissues were stained with PAS and Sirius red. Sclerosis index of glomerulus was calculated.

RESULTSRenal mass diminution was found in all the groups of aging rats. Scr was decreased in the group of aging rats with atorvastatin 1 mg/(kg x d). The level of blood-lipoids of aging rats was higher than that of young rats. The level of serum cholesterol and low-density lipoprotein (LDL) were decreased in first group (both P < 0.05) and only LDL decreased in second group (P < 0.05). Morphological changes of aging kidney were focal segmental glomerulosclerosis, widen of mesangial region, infiltration of inflammatory cells and sclerosis of arteriole. The treatment of atorvastatin improved the pathologic changes in the aging rats significantly, especially in the first group.

CONCLUSIONTaking atorvastatin for long time can notably improve the pathological changes of aging kidney. All these effects may be induced by lowing of blood-lipoids, relieving the sclerosis of renal arteriole and reducing the infiltration of inflammatory cells.

Aging ; physiology ; Animals ; Anticholesteremic Agents ; administration & dosage ; pharmacology ; Arteriosclerosis ; pathology ; prevention & control ; Atorvastatin Calcium ; Female ; Heptanoic Acids ; administration & dosage ; pharmacology ; Kidney ; pathology ; Kidney Diseases ; prevention & control ; Pyrroles ; administration & dosage ; pharmacology ; Rats ; Rats, Wistar ; Renal Artery ; pathology

OBJECTIVETo observe the effect of atorvastatin on eNOS synthesis in the vital organs of aging rats and explore its mechanism for protection against myocardial ischemia-reperfusion injury.

METHODSTwenty-month-old Wistar rats were given daily atorvastatin lavage for 4 months. Myocardial ischemia-reperfusion model was established by ligating the coronary artery. The rats were randomized into normal control group, untreated model group, medication without surgery group, and atorvastatin-treated surgical group. The content of eNOS in the heart, liver and kidneys was detected by Western blotting, and eNOS mRNA expression by RT-PCR. The effects of different doses of atorvastatin on eNOS expressions were also evaluated.

RESULTSAtorvastatin significantly promoted eNOS synthesis in the heart, liver and kidney of the rats (P<0.05) regardless of myocardial ischemia-reperfusion. A higher dose of atorvastatin caused a more obvious increase of eNOS protein and mRNA expression in the vital organs of the aging rats (P<0.05).

CONCLUSIONAtorvastatin can increase eNOS synthesis in the vital organs of aging rats, which partially explains the organ-protective effect of atorvastatin against myocardial ischemia- reperfusion.

Animals ; Atorvastatin Calcium ; Female ; Heptanoic Acids ; administration & dosage ; pharmacology ; Kidney ; metabolism ; Liver ; metabolism ; Male ; Myocardial Reperfusion Injury ; drug therapy ; metabolism ; Myocardium ; metabolism ; Nitric Oxide Synthase Type III ; genetics ; metabolism ; Pyrroles ; administration & dosage ; pharmacology ; Rats ; Rats, Wistar

OBJECTIVETo evaluate the efficacy of atorvastatin in preventing contrast agent-induced nephropathy (CIN) in patients undergoing coronary angiography and explore the mechanism.

METHODSA total of 180 patients undergoing coronary angiography or percutaneous coronary interventions (PCI) were randomized into regular dose and high dose atorvastatin groups (n=90). Serum creatinine (Scr), glomerular filtration rate (GFR), cystatin, peripheral blood levels of myeloperoxidase (MPO), malondialdehyde (MDA), and superoxide dismutase (SOD) before and after the procedure were compared between the two groups.

RESULTSThe incidence of CIN was significantly lower in high-dose atorvastatin group than in the regular dose group. At 48-72 h after the surgery, serum Scr and cystatin levels were significantly lower and eGFR was significantly higher in the high-dose group. At 24 h after the surgery, MPO and MDA levels were significantly lower, and SOD activity was significantly higher in high-dose group than in the regular dose group.

CONCLUSIONHigh-dose atorvastatin used before angiography is more effective than the regular dose in attenuating contrast agent-induced renal dysfunction, and its mechanism is related with the inhibition of oxidative stress.

Aged ; Atorvastatin Calcium ; Contrast Media ; adverse effects ; Coronary Angiography ; adverse effects ; Female ; Heptanoic Acids ; administration & dosage ; pharmacology ; therapeutic use ; Humans ; Kidney Diseases ; chemically induced ; prevention & control ; Male ; Middle Aged ; Oxidative Stress ; drug effects ; Pyrroles ; administration & dosage ; pharmacology ; therapeutic use

OBJECTIVETo compare the efficacy of high and low dose atorvastatin on preventing contrast induced nephropathy (CIN) in patients underwent diagnostic and therapeutic coronary intervention.

METHODSAll patients received atorvastatin 10 mg/d on the basis of hydrated therapy (n = 100) and high dose group received additional atorvastatin 80 mg at 12 to 24 hours before procedure (n = 50). Scr, Ccr, blood beta(2)-M, urine NAG/Cr, and urine osmolality before and after the procedure were compared between the groups.

RESULTSBaseline demographic characteristics and nephropathy risk factors were similar between groups. Ccr was significantly reduced while blood beta(2)-M and uric NAG/Cr were significantly increased in low dose group (all P < 0.05). Blood beta(2)-M in the high dose group was significantly lower than that in the low dose group at day 1 [(2.35 +/- 0.52) mg/L vs. (2.67 +/- 0.64) mg/L, P = 0.008], day 3 [(2.49 +/- 0.55) mg/L vs. (2.80 +/- 0.64) mg/L, P = 0.011] and day 5 [(2.29 +/- 0.53) mg/L vs. (2.56 +/- 0.66) mg/L, P = 0.026] post-procedure respectively;urine NAG/Cr in the high dose group was also significantly lower than that in the low dose group at day 1 [(1.19 +/- 0.30) U/mmol vs. (1.46 +/- 0.34) U/mmol, P < 0.001], day 3 [(1.30 +/- 0.30) U/mmol vs. (1.59 +/- 0.33) U/mmol, P < 0.001], and day 5 [(1.10 +/- 0.30) U/mmol vs. (1.34 +/- 0.35) U/mmol, P = 0.001] post-procedure respectively;Ccr in the high dose group was significantly higher than that in the low dose group at day 1 [(73.69 +/- 20.99) ml/min vs. (65.19 +/- 18.72) ml/min, P = 0.035], day 3 [(64.04 +/- 15.82) ml/min vs. (56.79 +/- 14.50) ml/min, P = 0.019]post-procedure respectively.

CONCLUSIONHigh dose atorvastatin use before angiography is superior than low dose atorvastatin on attenuating contrast induced renal dysfunction.

Aged ; Atorvastatin Calcium ; Contrast Media ; adverse effects ; Coronary Angiography ; methods ; Female ; Heptanoic Acids ; administration & dosage ; therapeutic use ; Humans ; Kidney Diseases ; chemically induced ; prevention & control ; Kidney Failure, Chronic ; chemically induced ; prevention & control ; Male ; Middle Aged ; Pyrroles ; administration & dosage ; therapeutic use