Androgen deprivation therapy, which is the standard treatment for metastatic prostate cancer, includes nonsteroidal antiandrogenic drugs, such as flutamide, nilutamide and bicalutamide. Of them, bicalutamide rarely induces interstitial pneumonia. We report a case of bicalutamide-induced interstitial pneumonia. A 68-year old male diagnosed with prostate cancer and multiple bone metastases presented with dry cough and low grade fever for 3 days. He had taken bicalutamide (50 mg/day) for 13 months. High resolution computed tomography revealed ground glass opacity in his right upper lung. The laboratory studies showed no eosinophilia in the serum and bronchoalveolar lavage fluid. Despite the use of antimicrobial agents for 2 weeks, the extent of the lung lesions increased to the left upper and right lower lung. He had no environmental exposure, collagen vascular disease and microbiological causes. Under the suspicion of bicalutamide-induced interstitial pneumonia, bicalutamide was stopped and prednisolone (1 mg/kg/day) was initiated. The symptoms and radiologic abnormalities were resolved with residual minimal fibrosis.
Anilides ; Anti-Infective Agents ; Bronchoalveolar Lavage Fluid ; Collagen ; Cough ; Environmental Exposure ; Eosinophilia ; Fever ; Fibrosis ; Flutamide ; Glass ; Humans ; Imidazolidines ; Lung ; Lung Diseases, Interstitial ; Male ; Neoplasm Metastasis ; Nitriles ; Prednisolone ; Prostatic Neoplasms ; Tosyl Compounds ; Vascular Diseases

OBJECTIVE: To investigate the timing of reaching maximum improvement of the lower urinary tract symptoms (LUTS) in patients with advanced prostate cancer treated with maximal androgen blockade(MAB), and to provide guidelines for the treatment program. METHODS: We collected the data of 45 advanced prostate cancer patients complicated with lower urinary tract symptoms who were treated by MAB. The international prostate symptom score (IPSS) and maximum urinary flow rate (Qmax) were selected as indicators reflecting the degree of lower urinary tract symptoms and were observed before the MAB, 3, 6, and 9 months after the patients received MAB. We also observed the changes of prostate volume and analyzed the role of MAB in improving LUTS in patients with prostate cancer. RESULTS: The IPSS and Qmax had significant difference between the 3rd month after the patients received MAB and before the MAB (P<0.05). No significant difference was found between the 3rd month and the 6th month after the patients received MAB (P>0.05). The prostate volume had significant difference in the 3rd month and the 6th month (P<0.05), but no significant difference in the 6th month and the 9th month (P>0.05). CONCLUSION MAB for patients with advanced prostate cancer can improve their lower urinary tract symptoms, whose main effect is presented in the 3rd months after the androgen deprivation therapy.
Aged ; Aged, 80 and over ; Androgen Antagonists ; therapeutic use ; Anilides ; therapeutic use ; Flutamide ; therapeutic use ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Nitriles ; therapeutic use ; Prostatic Neoplasms ; complications ; drug therapy ; Tosyl Compounds ; therapeutic use ; Urination Disorders ; drug therapy ; etiology

A total of 62 leprosy patients, 47 lepromatous type, 9 tuberculoid, 5 borderline group and 1 indeterminate group, have been treated with a synthesized thiocarbanilide L-4, and the effectiveness of L-4 administration in the treatment of leprosy is evaluated on the basis of clinical and bacteriological improvements. The results are summarized and conc1uded as follows; 1. L-4, contained in gelatin capsule, can be safely administered orally to the patients through slow induction, from initial dosages of 50 mg to 100 mg dai1y to the therapeutic maintenance levels of 200 mg to 300 mg daily, for a period of time. 2. L-4 administration has brought apparent and remarkable improvement in clinical symptoms of the patients after a relatively short period of medication compared with that of DDS administration. 3. Changes of SFG values caused by L-4 administration were much speedier than, (or, at least, equivalent to) the effect caused by DDS. The changes of SFG values, in general, synchronized fairly well with clinical improvement of the patients. 4. Lepromatous cases with leprosy reaction or sulfone allergy responded well to L-4 medication with remarkable clinical improvement, and prolonged administration of L-4 did not provoke such a precipitating action to leprosy reaction as did DDS.
Adolescent ; Adult ; Anilides/chemical synthesis ; Anilides/therapeutic use* ; Anti-Infective Agents/chemical synthesis ; Anti-Infective Agents/therapeutic use* ; Child ; Female ; Human ; Leprosy/drug therapy* ; Male ; Middle Age ; Sulfur*

AIMTo evaluate the long-term effectiveness, side effects and compliance rates of two types of drugs (luteinizing hormone-releasing hormone [LHRH] agonist and antiandrogen) that were used individually to treat patients with localized prostate cancer (T1-2) at our institution.

METHODSNinety-seven patients who were diagnosed in the period from April 1997 to January 2000 as having clinically localized prostate cancer (T1-2) received either LHRH agonist (leuprolide acetate 7.5 mg/month) monotherapy (group 1, n = 62) or antiandrogen monotherapy (group 2, n = 35; 18 received bicalutamide 50 mg q.d., 13 received nilutamide 150 mg t.i.d. and 4 received flutamide 250 mg t.i.d.). The mean age in both groups was 76 years.

RESULTSThe mean follow-up time was (50.8 +/- 8.5) months in group 1 and (43.1 +/- 2.2) months in group 2. Prostate-specific antigen (PSA) levels rose in only 1 of the 62 patients (1.6%) in group 1, and in 20 of the 35 patients (57.1%) in group 2. In group 2, 10 of the 20 patients (50%) with increasing PSA levels were treated with LHRH salvage therapy, and eight (80%) responded. Hot flashes (54.8%) and lethargy (41.9%) were the most common side effects in group 1. In contrast, nipple-tenderness (40%) and light-dark adaptation (17.1%) were more often seen in group 2. Only 1 of the 62 patients (1.6%) in group 1 switched to another medication because of adverse side effects; whereas 8 of the 35 patients (22.9%) in group 2 did so.

CONCLUSIONUnlike antiandrogen monotherapy, LHRH agonist monotherapy provided long-term durable control of localized prostate cancer (T1-2). It can also be an effective treatment option for patients whose disease failed to respond to antiandrogen monotherapy. The limitations of our study are the lack of health outcomes analysis and a small sample size.

Aged ; Aged, 80 and over ; Androgen Antagonists ; adverse effects ; therapeutic use ; Anilides ; adverse effects ; therapeutic use ; Flutamide ; adverse effects ; therapeutic use ; Gonadotropin-Releasing Hormone ; agonists ; Humans ; Imidazolidines ; adverse effects ; therapeutic use ; Leuprolide ; adverse effects ; therapeutic use ; Male ; Nitriles ; adverse effects ; therapeutic use ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms ; drug therapy ; Retrospective Studies ; Tosyl Compounds ; adverse effects ; therapeutic use

Even in the era of novel targeted agents, switching to a second-line nonsteroidal antiandrogen (NSAA) is still widely used in treating metastatic castration-resistant prostate cancer (mCRPC), especially in undeveloped countries. However, whether prior treatment with a second-line NSAA would impact the efficacy of abiraterone acetate (Abi) remains uncertain. In the current study, 87 mCRPC patients treated with Abi were analyzed. Among them, 21 were treated with a second-line NSAA (from bicalutamide to flutamide) before receiving abiraterone, while the remaining 66 received Abi directly. Therapeutic efficacy of Abi was compared between those with and without prior second-line NSAA using Kaplan-Meier curves, log-rank test, and Cox regression models. The therapeutic efficacy of Abi was similar between those with or without the prior switching treatment of flutamide, in terms of either prostate-specific antigen progression-free survival (PSA-PFS, 5.5 vs 5.6 months, P = 0.967), radiographic progression-free survival (rPFS, 12.8 vs 13.4 months, P = 0.508), overall survival (OS, not reached vs 30.6 months, P = 0.606), or PSA-response rate (71.4% [15/21] vs 60.6% [40/66], P = 0.370). This is the first time that the impact of prior switching of treatment to a second-line NSAA on the efficacy of Abi in mCRPC patients has been addressed. Our data support that, use of prior sequential bicalutamide and flutamide does not seem to preclude response to abiraterone, although larger cohort studies and, ideally, a randomized controlled trial are needed. These findings will facilitate doctors' decision-making in the treatment of mCRPC patients, especially for those with previous experience of switching NSAA second-line treatments in the clinic.
Abiraterone Acetate/therapeutic use* ; Aged ; Aged, 80 and over ; Androgen Antagonists/therapeutic use* ; Anilides/therapeutic use* ; Antineoplastic Agents, Hormonal/therapeutic use* ; Disease-Free Survival ; Female ; Flutamide/therapeutic use* ; Humans ; Kaplan-Meier Estimate ; Male ; Nitriles/therapeutic use* ; Nonsteroidal Anti-Androgens/therapeutic use* ; Prostate-Specific Antigen/analysis* ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Retrospective Studies ; Survival Analysis ; Tosyl Compounds/therapeutic use* ; Treatment Outcome

OBJECTIVETo investigate the effect of c-Met inhibitor cabozantinib (XL-184) in inhibiting Listeria monocytogenes (LM) from invading Caco-2 cells to reduce the cell injury.

METHODSThe cell invasion capacity of LM was assayed in Caco-2 cells incubated with different doses of XL-184 for different durations. Caco-2 cells incubated with XL-184 were seeded on the upper room of the transwell chamber, and the cell monolayer was exposed to LM infection followed by addition of horseradish peroxidase (HRP). The trans-epithelial electric resistance (TEER), HRP concentration and LM colony-forming unit (CFU) were measured in the cell monolayer. Fluorescent staining was used to evaluate the cell viability, and LDH release from the cells was examined to assess the changes in cell membrane permeability.

RESULTSXL-184 significantly decreased LM invasion rate in Caco-2 cells in a dose- and time-dependent manner (P=0.000), and this effect was enhanced by co-incubation of the cells with ampicillin (P<0.05). In the cell membrane permeability assay in the monolayer cells, XL-184 markedly inhibited LM-induced reduction of TEER (P<0.05) and significantly suppressed LM-induced enhancement of cell membrane permeability shown by reduced HRP concentration and LM count in the lower chamber (P=0.000). The cells infected with LM showed significantly lowered cell viability, which was rescued by XL-184 (P<0.01); XL-184 also dose-dependently reduced LDH release from the cells (P<0.05).

CONCLUSIONSXL-184 can suppress LM invasion in Caco-2 cells to reduce the cell injury, suggesting its value as a promising candidate agent for prevention and treatment of LM infections.

Anilides ; pharmacology ; Caco-2 Cells ; Cell Membrane Permeability ; drug effects ; Cell Survival ; Humans ; Listeria monocytogenes ; drug effects ; Pyridines ; pharmacology

OBJECTIVETo explore the chemopreventive effect of curcumin on DMH induced colorectal carcinogenesis and the underlining mechanism.

METHODSTotally 40 Wistar rats were divided into the model group and the curcumin group by random digit table, 20 in each group. Meanwhile, a normal control group was set up (n =10). A colorectal cancer model was induced by subcutaneously injecting 20 mg/kg DMH. The tumor incidence and the inhibition rate were calculated. The effect of curcumin on the expression of peroxisome proliferator-activated receptor gamma (PPARγ) in rat colon mucosal tissues was observed using immunohistochemistry and Western blot. HT 29 cell line were cultured and divided into a control group, the curcumin + GW9662 (2-chloro-5-nitro-N-4-phenylbenzamide) intervention group, and the curcumin group. The inhibition of different concentrations curcumin on HT29 cell line was detected using MTT. The expression of curcumin on PPARy was also detected using Western blot.

RESULTSThe tumor incidence was 80. 00% (12/15 cases) in the model group, obviously higher than that of the curcumin group (58. 82%, 10/17 cases, P <0. 05). The inhibition rate of curcumin on DMH induced colorected carcinoma reached 26. 46%. Compared with the normal control group, the expression of PPARγ protein was significantly increased in the curcumin group and the model group (P <0. 01). Compared with the model group at the same time point, the expression of PPARy protein was significantly enhanced in the curcumin group (P <0. 05). MTT analysis showed that curcumin could inhibit the proliferation of in vitro HT 29 cells in dose and time dependent manners. The expression of PPARy protein was significantly increased in the GW9662 group and the curcumin group, showing statistical difference when compared with the normal control group (P <0. 01). Compared with the GW9662 group, the expression of PPARγ protein was significantly increased in the curcumin group (P <0. 01).

CONCLUSIONCurcumin could inhibit DMH-induced rat colorectal carcinogenesis and the growth of in vitro cultured HT 29 cell line, which might be achieved by activating PPARy signal transduction pathway.

Anilides ; Animals ; Carcinogenesis ; Colorectal Neoplasms ; drug therapy ; metabolism ; Curcumin ; pharmacology ; therapeutic use ; PPAR gamma ; metabolism ; Rats ; Rats, Wistar ; Signal Transduction

Endogenously eliminating the hematoma is a favorable strategy in addressing intracerebral hemorrhage (ICH). This study sought to determine the role of retinoid X receptor-α (RXR-α) in the context of hematoma absorption after ICH. Our results showed that pharmacologically activating RXR-α with bexarotene significantly accelerated hematoma clearance and alleviated neurological dysfunction after ICH. RXR-α was expressed in microglia/macrophages, neurons, and astrocytes. Mechanistically, bexarotene promoted the nuclear translocation of RXR-α and PPAR-γ, as well as reducing neuroinflammation by modulating microglia/macrophage reprograming from the M1 into the M2 phenotype. Furthermore, all the beneficial effects of RXR-α in ICH were reversed by the PPAR-γ inhibitor GW9662. In conclusion, the pharmacological activation of RXR-α confers robust neuroprotection against ICH by accelerating hematoma clearance and repolarizing microglia/macrophages towards the M2 phenotype through PPAR-γ-related mechanisms. Our data support the notion that RXR-α might be a promising therapeutic target for ICH.
Anilides/pharmacology* ; Cerebral Hemorrhage/drug therapy* ; Hematoma/drug therapy* ; Humans ; Macrophages ; Microglia ; Neuroprotection ; PPAR gamma ; Retinoid X Receptor alpha

The changes of methemoglobin concentration in the blood after the use of lidocatine or Marcaine were investigated in the human and the rabbits. In the human the drugs were give by the epidural route and intramuscularly in rabbits. Lidocaine did not increase the methemoglobin concentration in humans but marcaine increased the methemoglobin concentration in the blood.
Bupivacaine* ; Humans ; Lidocaine ; Methemoglobin* ; Rabbits

This study aims to detect the expression of metabotropic glutamate receptors (mGluRs) in lung carcinoma A549 cells, and to investigate the effects of mGluR8 and mGluR4 activation on the growth of A549 cells in vitro. The mRNA expression levels of the 8 subtypes of mGluRs in A549 cells were determined by real-time PCR. Immunohistochemistry was used to analyze the protein expression of mGluR4 and mGluR8 in A549 cells and lung tissue sections obtained from lung adenocarcinoma patients. To observe the effects of mGluR8 and mGluR4 activation on the growth of A549 cells, the cultured cells were treated with (S)-3,4-DCPG (an agonist of mGluR8) and VU0155041 (an agonist of mGluR4), respectively, and then the cell viability was analyzed by CCK-8 kit, the percentage of DNA synthesis was detected by EdU incorporation, and the apoptosis of the cells was measured by hoechst 33258 staining and flow cytometry. The results showed that there were low expressions of mGluR1, mGluR5, mGluR6, mGluR7 mRNA, no expression of mGluR2 and mGluR3 mRNA, and high expressions of mGluR8 and mGluR4 mRNA in A549 cells. Accordingly, there were also mGluR4 and mGluR8 protein expressions in the A549 cells and the lung adenocarcinoma tissue sections. VU0155041 had no effect on the growth of A549 cells, but (S)-3,4-DCPG significantly decreased the cells' growth in a dose-dependent manner and increased the apoptosis of the cells. The results revealed a role of mGluR8 in the growth and apoptosis of A549 cells and suggested a potential target for clinical treatment of lung cancer.
Anilides ; pharmacology ; Apoptosis ; Benzoates ; pharmacology ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; Cyclohexanecarboxylic Acids ; pharmacology ; Glycine ; analogs & derivatives ; pharmacology ; Humans ; Lung Neoplasms ; pathology ; Receptors, Metabotropic Glutamate ; physiology