No abstract available.
Antineoplastic Agents/*adverse effects ; Female ; Humans ; Indoles/*adverse effects ; Male ; Proteinuria/*chemically induced ; Pyrroles/*adverse effects ; Renal Insufficiency/*chemically induced

Drug Combinations ; Drug Eruptions ; diagnosis ; etiology ; Humans ; Hypolipidemic Agents ; adverse effects ; Indoles ; adverse effects ; Male ; Middle Aged ; Niacin ; adverse effects ; Skin Diseases, Vesiculobullous ; chemically induced ; diagnosis

Objective: To evaluate the safety and efficacy of anlotinib plus irinotecan in the second-line treatment of patients with metastatic colorectal cancer (mCRC). Methods: This prospective phase 1/2 study was conducted in 2 centers in China (Cancer Hospital of Chinese Academy of Medical Sciences and Jiangsu Province Hospital). We enrolled patients with mCRC whose disease had progressed after first-line systemic therapy and had not previously treated with irinotecan to receive anlotinib plus irinotecan. In the phase 1 of the trial, patients received anlotinib (8 mg, 10 mg or 12 mg, po, 2 weeks on/1 week off) in combination with fixed-dose irinotecan (180 mg/m(2), iv, q2w) to define the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). In the phase 2, patients were treated with the RP2D of anlotinib and irinotecan. The primary endpoints were MTD and objective response rate (ORR). Results: From May 2018 to January 2020, a total of 31 patients with mCRC were enrolled. Anlotinib was well tolerated in combination with irinotecan with no MTD identified in the phase 1, and the RP2D was 12 mg. Thirty patients were evaluable for efficacy analysis. Eight patients achieved partial response, and 21 had stable disease, 1 had progressive disease. The ORR was 25.8% and the disease control rate was 93.5%. With a median follow-up duration of 29.5 months, the median progression-free survival and overall survival were 6.9 months (95% CI: 3.7, 9.3) and 17.6 months (95% CI: 12.4, not evaluated), respectively. The most common grade 3 treatment-related adverse events (≥10%) were neutropenia (25.8%) and diarrhea (16.1%). There was no treatment-related death. Conclusion: The combination of anlotinib and irinotecan has promising anti-tumor activity in the second-line treatment of mCRC with a manageable safety profile.
Humans ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Colorectal Neoplasms/pathology* ; Indoles/therapeutic use* ; Irinotecan/therapeutic use* ; Prospective Studies

ObjectiveTo investigate the therapeutic effects of commonly used selective α-adrenergic receptor antagonists (α-ARA) on benign prostatic hyperplasia (BPH).

METHODSPubMed, Embase and CNKI databases were searched for the literature about selective α-ARAs for the treatment of BPH and the information was extracted on the common adverse reactions in the course of treatment. Multivariate meta-analysis was conducted to investigate the therapeutic effects of different α-ARAs.

RESULTSThe total rates of adverse effects of silodosin and tamsulosin were the highest, 51.9% and 34.0% respectively, with the highest incidences of headache (38.3%), weakness (23.6%) and dizziness (17.5%). Besides, tamsulosin ranked the first in inducing sexual dysfunction of the male patients with BPH (70.4%).

CONCLUSIONSDoxazosin is preferable as the first-choice treatment of BPH for its therapeutic effect and improvement of the patient's quality of life. Silodosin and tamsulosin, however, can be selectively used according to the patient's specific tolerance to different adverse effects.

Adrenergic alpha-Antagonists ; adverse effects ; therapeutic use ; Doxazosin ; adverse effects ; therapeutic use ; Humans ; Indoles ; adverse effects ; therapeutic use ; Male ; Network Meta-Analysis ; Prostatic Hyperplasia ; drug therapy ; Quality of Life ; Sexual Dysfunction, Physiological ; chemically induced ; Tamsulosin ; adverse effects ; therapeutic use

BACKGROUNDFamitinib is a novel and potent multitargeting receptor tyrosine kinase inhibitor. The phase I clinical study showed that famitinib was well tolerated and had a broad anti-tumor spectrum. The purpose of this study was to examine the efficacy and safety of famitinib for the treatment of metastatic renal cell carcinoma (mRCC).

METHODSThe data of famitinib in treating patients with mRCC from the single-center phases I and II clinical trials were analyzed. Famitinib was administered orally at the dose of 13-30 mg once daily until tumor progression, occurrence of intolerable adverse reactions or withdrawal of the informed consent.

RESULTSA total of 24 patients with mRCC were treated including 17 patients at a dose of 25 mg once daily, 4 patients at a dose of 27 mg and 1 patient each at a dose of 13 mg, 20 mg and 30 mg, respectively. Twelve (50.0%) patients achieved partial response (PR) and 9 patients achieved stable disease (SD). Progressive disease was found in 3 (12.5%) patients. The disease control rate was 87.5%. The median follow-up time was 17.6 months; the median progression free survival (PFS) was 10.7 (95% CI 7.0-14.4) months; and the estimated median overall survival (OS) time was 33.0 (95% CI 8.7-57.3) months. The adverse drug reactions mainly included hypertension (54.1%), hand-foot skin reactions (45.8%), diarrhea (33.3%), mucositis (29.2%), neutropenia (45.8%), thrombocytopenia (29.2%), hyperlipidemia (41.7%) and proteinuria (41.7%). The incidence rate of grades 3 and 4 adverse events was low, mainly including hypertension 12.5%, hand-foot skin reactions 4.2%, neutropenia 4.2%, thrombocytopenia 4.2%, hyperlipidemia 4.2% and proteinuria 12.5%.

CONCLUSIONSFamitinib has significant anti-tumor activity in mRCC. The common adverse reactions are generally manageable.

Adult ; Aged ; Carcinoma, Renal Cell ; drug therapy ; Female ; Humans ; Indoles ; adverse effects ; therapeutic use ; Kidney Neoplasms ; drug therapy ; Male ; Protein Kinase Inhibitors ; Pyrroles ; adverse effects ; therapeutic use ; Retrospective Studies ; Treatment Outcome ; Young Adult

Adult ; Animals ; Colitis ; chemically induced ; pathology ; Colon ; pathology ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; Female ; Humans ; Indigo Carmine ; Indoles ; administration & dosage ; adverse effects ; Male ; Middle Aged ; Phytotherapy ; Psoriasis ; drug therapy ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effect of different concentrations of glucose on the permeability of human umbilical vein endothelial cell monolayer and the protective effect of protein kinase C (PKC) inhibitor Ro-31-8425 against high-glucose exposure.

METHODSCultured human umbilical vein endothelial cell line EA.hy926 cells were exposed to 5.5 mmol/L glucose (control) and high-concentration glucose (10, 15, 20, 25.5, and 30 mmol/L), and the endothelial monolayer permeability was assessed by measuring the flux of FITC-labeled dextran (FITC-DΧ) across the endothelial cells. The cultured EA.hy926 cells were treated with 5.5 mmol/L glucose +saline, high glucose (25.5 mmol/L) +saline, or high glucose (25.5 mmol/L) +Ro-31-8425(10 µmol/L), and the level of PKC phosphorylation and endothelial monolayer permeability were evaluated.

RESULTSHigh glucose dose-dependently increased the permeability of the endothelial cell monolayer (P<0.01), and glucose at 25.5 mmol/L significantly increased the phosphorylation level of PKCα and PKCβ II in the cells (P<0.01). Treatment with 10 µmol/L Ro-31-8425 obviously attenuated high-glucose-induced PKCα and PKCβ II phosphorylation (P<0.01) as well as the increase of the cell monolayer permeability (P<0.01).

CONCLUSIONSHigh glucose increases the hyperpermeability of human umbilical vein endothelial cell monolayer mediated by the phosphorylation of PKC, and the PKC inhibitor Ro-31-8425 can reverse such effects.

Capillary Permeability ; drug effects ; Cells, Cultured ; Endothelium, Vascular ; drug effects ; metabolism ; Glucose ; adverse effects ; Human Umbilical Vein Endothelial Cells ; drug effects ; Humans ; Indoles ; pharmacology ; Maleimides ; pharmacology ; Protein Kinase C ; antagonists & inhibitors

OBJECTIVETo investigate the effect of fluvastatin on lysophosphatidylcholine (LPC)-induced ventricular arrhythmias and its mechanism.

METHODSTwenty male SD rats were randomly allocated into two equal groups, namely LPC treatment group and fluvastatin pretreatment group. Langendorff apparatus was used for cardiac perfusion ex vivo with 5 µmol/L LPC for 5 min followed by washing for 30 min in LPC treatment group, and in fluvastatin pretreatment group, a 30-min perfusion with 10 µmol/L fluvastatin was administered before LPC perfusion. The LPC-induced nonselective cation current (I(NSC)) in the ventricular myocytes was recorded using the whole-cell voltage-clamp method.

RESULTSFluvastatin significantly inhibited LPC-induced ventricular tachyarrhythmia/fibrillation and I(NSC). The small G-protein Rho inhibitor (C3) and Rho-kinase inhibitor (Y-27632) in the pipette solution also suppressed LPC-induced I(NSC).

CONCLUSIONFluvastatin offers cardiac protection against LPC by inhibiting LPC-induced I(NSC). LPC induces fatal arrhythmia via a Rho/Rho-kinase-mediated pathway.

Animals ; Arrhythmias, Cardiac ; chemically induced ; metabolism ; Drug Antagonism ; Fatty Acids, Monounsaturated ; pharmacology ; Indoles ; pharmacology ; Ion Channels ; drug effects ; Lysophosphatidylcholines ; adverse effects ; Male ; Myocytes, Cardiac ; metabolism ; Rats ; Rats, Sprague-Dawley ; rho-Associated Kinases ; metabolism

Acute generalized exanthematous pustulosis is a rare severe pustular cutaneous adverse reaction characterized by a rapid clinical course with typical histological findings. It is accompanied by fever and acute eruption of non-follicular pustules overlying erythrodermic skin. The causative agents are most frequently antibacterial drugs. We present a patient with acute generalized exanthematous pustulosis caused by methylene blue and indigotin dyes.
Acute Generalized Exanthematous Pustulosis/*chemically induced/drug therapy/pathology ; Administration, Oral ; Adrenal Cortex Hormones/therapeutic use ; Aged ; Biopsy ; Coloring Agents/administration & dosage/*adverse effects ; Humans ; Indoles/administration & dosage/*adverse effects ; Intradermal Tests ; Male ; Methylene Blue/administration & dosage/*adverse effects ; Skin/*drug effects/pathology ; Treatment Outcome

Sunitinib as a multitarget tyrosine kinase inhibitor is one of the anti-tumor agents, approved by the United States Food and Drug Administration to use treat gastrointestinal stromal tumor and metastatic renal cell carcinoma. The agent is known to commonly induce adverse reactions such as fatigue, nausea, diarrhea, stomatitis, esophagitis, hypertension, skin toxicity, reduciton in cardiac output of left ventricle, and hypothyroidism. However, it has been reported to rarely induce adverse reactions such as nephrotic syndrome and irreversible reduction in renal functions, and cases of intestinal perforation or pneumatosis interstinalis as such reactions have been consistently reported. In this report, a 66-year old man showing abdominal pain had renal cell carcinoma and history of sunitinib at a dosage of 50 mg/day on a 4-weeks-on, 2-weeks-off schedule. Seven days after the third cycle he was referred to the hospital because of abdominal pain. Computed tomography showed pneumoperitoneum with linear pneumatosis intestinalis in his small bowel. The patient underwent surgical exploration that confirmed the pneumatosis intestinalis at 100 cm distal to Treitz's ligament. We report a rare case of intestinal perforation with pneumatosis intestinalis after administration of sunitinib to a patient with metastatic renal cell carcinoma.
Aged ; Antineoplastic Agents/adverse effects/*therapeutic use ; Carcinoma, Renal Cell/*drug therapy ; Drug Administration Schedule ; Humans ; Indoles/adverse effects/*therapeutic use ; Intestinal Perforation/*diagnosis/etiology/surgery ; Kidney Neoplasms/*drug therapy ; Lung/radiography ; Male ; Pneumatosis Cystoides Intestinalis/*diagnosis/etiology ; Positron-Emission Tomography ; Pyrroles/adverse effects/*therapeutic use ; Tomography, X-Ray Computed