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  • Blackwell Science Pty  (34)
  • The American Association for Cancer Research (AACR)  (34)
  • Macmillian Magazines Ltd.  (21)
  • 1
    Publication Date: 2018-11-02
    Description: The most commonly utilized class of chemotherapeutic agents administered as a first-line therapy are antimitotic drugs; however, their clinical success is often impeded by chemoresistance and disease relapse. Hence, a better understanding of the cellular pathways underlying escape from cell death is critical. Mitotic slippage describes the cellular process where cells exit antimitotic drug-enforced mitotic arrest and "slip" into interphase without proper chromosome segregation and cytokinesis. The current report explores the cell fate consequence following mitotic slippage and assesses a major outcome following treatment with many chemotherapies, therapy-induced senescence. It was found that cells postslippage entered senescence and could impart the senescence-associated secretory phenotype (SASP). SASP factor production elicited paracrine protumorigenic effects, such as migration, invasion, and vascularization. Both senescence and SASP factor development were found to be dependent on autophagy. Autophagy induction during mitotic slippage involved the autophagy activator AMPK and endoplasmic reticulum stress response protein PERK. Pharmacologic inhibition of autophagy or silencing of autophagy-related ATG5 led to a bypass of G 1 arrest senescence, reduced SASP-associated paracrine tumorigenic effects, and increased DNA damage after S-phase entry with a concomitant increase in apoptosis. Consistent with this, the autophagy inhibitor chloroquine and microtubule-stabilizing drug paclitaxel synergistically inhibited tumor growth in mice. Sensitivity to this combinatorial treatment was dependent on p53 status, an important factor to consider before treatment. Implications: Clinical regimens targeting senescence and SASP could provide a potential effective combinatorial strategy with antimitotic drugs. Mol Cancer Res; 16(11); 1625–40. ©2018 AACR .
    Print ISSN: 1541-7786
    Electronic ISSN: 1557-3125
    Topics: Medicine
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  • 2
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Tetramethylpyrazine (TMP) is one of the active principles contained in Ligusticum chuanxiong Hort. (Umbelliferae), a herb that has been used widely in China to treat vascular disorders.2. In an attempt to elucidate the possible mechanisms of action of TMP, the effect of TMP on intracellular calcium concentrations ([Ca2+]i) was investigated in cultured vascular smooth muscle (A7r5) cells using the Ca2+-sensitive dye Fura-2 as an indicator.3. The increase in [Ca2+]i in A7r5 cells produced by vasopressin (1 µmol/L) or phenylephrine (1 µmol/L) was attenuated by TMP in a concentration-dependent manner. Only inhibitors specific to ATP-sensitive potassium (KATP) channels or small conductance calcium-activated potassium (SKCa) channels attenuated the action of TMP (10 µmol/L) on [Ca2+]i. However, blockers of other K+ channels failed to modify the inhibitory action of TMP (10 µmol/L) on [Ca2+]i.4. The action of TMP on membrane potential in A7r5 cells was monitored by the fluorescence of bisoxonol. Tetramethylpyrazine caused a concentration-dependent inhibition of changes in membrane potential elicited by KCl (20 mmol/L) or phenylephrine (1 µmol/L), an effect that was totally reversed by glibenclamide (100 µmol/L) and apamin (100 nmol/L) in combination.5. The results obtained indicate that the decrease in [Ca2+]i in A7r5 cells produced by TMP is mediated mainly by opening of KATP and/or SKCa channels.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Sulphotransferases are a superfamily of enzymes involved in both detoxification and bioactivation of endogenous and exogenous compounds. The arylsulphotransferase SULT1A1 has been implicated in a decreased activity and thermostability when the wild-type arginine at position 213 of the coding sequence is substituted by a histidine. SULT1A1 is the isoform primarily associated with the conversion of dietary N-OH arylamines to DNA binding adducts and is therefore of interest to determine whether this polymorphism is linked to colorectal cancer.2. Genotyping, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, was performed using DNA samples of healthy control subjects (n = 402) and patients with histologically proven colorectal cancer (n = 383). Both control and test populations possessed similar frequencies for the mutant allele (32.1 and 31%, respectively; P = 0.935). Results were not altered when age and gender were considered as potential confounders in a logistic regression analysis.3. Examination of the sulphonating ability of the two allozymes with respect to the substrates p-nitrophenol and paracetamol showed that the affinity and rate of sulphonation was unaffected by substitution of arginine to histidine at position 213 of the amino acid sequence.4. From this study, we conclude that the SULT1A1 R213H polymorphism is not linked with colorectal cancer in this elderly Australian population.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Fluorescent Ca2+ indicators, such as fura-2/AM and calcium green-1, have become one of the most popular tools for measuring intracellular calcium ([Ca2+]i).2. Electrical stimulation triggers a cascade of events in the cardiac muscle, which results in a [Ca2+]i transient and, eventually, contraction. The events that occur in electrically induced cardiac myocytes mimic the normal physiological events in vivo.3. The electrically induced [Ca2+]i transient represents influx of Ca2+ from outside and mobilization of Ca2+ from the intracellular store and is directly related to contraction. Thus, it is more important to determine the electrically induced [Ca2+]i transient than [Ca2+]i. The [Ca2+]i transient can be easily measured with the spectrofluorescence method using fura 2/AM as the Ca2+ indicator in a single ventricular myocyte preparation.4. We made use of the results of studies on carbachol, tetrandrine and cardiotoxin to illustrate the usefulness of the electrically induced [Ca2+]i transient in the study of actions of cardiac drugs.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. The effects of κ opioid receptor stimulation on cardiac rhythm and the underlying signal pathways were investigated in the rat.2. Stimulation of κ opioid receptors with 40–50 μmol/L U50 488H, a selective κ opioid receptor agonist, induced dysrhythmias and increased inositol 1,4,5-trisphosphate (IP3) production in rat isolated, perfused heart. The pro-arrhythmic effects of U50 488H were abolished by 5 μmol/L nor- binaltorphimine (nor-BNI), a specific κ opioid receptor antagonist.3. The effect of U50 488H on cardiac dysrhythmia and IP3 production were abolished by 1 mmol/L neomycin and streptomycin, phospholipase C (PLC) inhibitors.4. At 1 μmol/L, U50 488H, which itself has no effect on cardiac rhythm and IP3 production, significantly attenuated the potentiating effect of 1 μmol/L noradrenaline (NA) on dysrhythmias, which were induced by low flow in the isolated heart. The effects of U50 488H were abolished by 1 μmol/L nor-BNI. Cytosolic cAMP production was augmented by 1 μmol/L NA and this was significantly attenuated by 1 μmol/L U50 488H.5. At 1 μmol/L, U50 488H also reduced [Ca2+]i oscillations induced by 0.5 μmol/L NA and 0.5 μmol/L forskolin, an activator of adenylate cyclase (AC).6. In conclusion, U50 488H exerted pro- and anti-arrhythmic actions at high and lower concentrations, respectively. The former effect was mediated via the PLC/IP3 pathway, while the latter was mediated via the AC/cAMP pathway.
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  • 6
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Backgrounds and Aims:  There is relatively little data on the seroprevalence of Helicobacter pylori in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). This study aims at establishing the seroprevalence of and the factors associated with H. pylori infection in Chinese CAPD patients.Methods:  All CAPD patients from a single dialysis centre were invited to participate in the study. Diagnosis of H. pylori infection was made serologically by the pylori DTect ELISA method. Dyspeptic symptoms were assessed by the Hong Kong Index of Dyspepsia (HKID) Questionnaire. Demographic, clinical and laboratory parameters were correlated with the H. pylori serology results.Results:  One hundred and thirty-six Chinese CAPD patients were included in the study. The mean age of the patients was 61.8 ± 12.5 years with a male to female ratio of 1:1.4. The mean duration of CAPD was 54 ± 42 months. Thirty-five patients (26%) have positive serology against H. pylori. Nineteen patients had a HKID score of 〉16. There was no association between H. pylori seropositivity and dyspeptic symptoms (P = 0.62). Patients who were seropositive for H. pylori were significantly older (64.9 ± 9.5 years vs 60.7 ± 13.2 years, P 〈 0.05) and had lower KT/V-values than patients who were seronegative for H. pylori (1.88 ± 0.3 vs 2.03 ± 0.3, P 〈 0.05). Patients with positive or negative H. pylori serological status did not differ in terms of demographic parameters (e.g. sex, duration of CAPD), clinical factors (e.g. bodyweight, body mass index, hepatitis status, use of H2 antagonists or proton pump inhibitors) and laboratory data (e.g. haemoglobin, serum urea, creatinine, albumin and parathyroid hormone levels).Conclusions:  The seroprevalence of H. pylori infection among Chinese CAPD patients is 26%. Helicobacter pylori seropositivity is not associated with dyspepsia. Older age and lower KT/V-values appear to be associated with the development of H. pylori seropositivity in our dialysis population.
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  • 8
    ISSN: 1442-2042
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract  Aim: To compare bacillus Calmette-Guerin (BCG) with epirubicin in adjuvant therapy of superficial bladder transitional cell carcinoma, with respect to recurrence, progression and survival. Prognostic factors are also evaluated.Methods: Between October 1991 and September 1999, all patients harboring superficial bladder cancers (Ta or T1) with any of the relevant criteria (stage 〉 a, grade 〉 1, size 〉 1 cm, multiple or recurrent tumors), after complete transurethral resection were randomized to receive either 81 mg Connaught strain BCG or 50 mg epirubicin. Patients with recurrences were eligible to crossover, even repeatedly, until progression. Recurrence, progression and survival were analyzed in relation to initial treatment, patient characteristics and tumor characteristics.Results: There were 209 patients included in the study, 149 men and 60 women. The mean age was 69.9 years (range, 24–92). The BCG group consisted of 102 patients and the epirubicin group contained 107 patients. Final analysis was made at a median follow up of 23, 47 and 61 months for recurrence, progression and survival, respectively. The 10-year Kaplan-Meier estimates for recurrence-free, progression-free and disease-specific survival were 61%, 78% and 80%, respectively, for the BCG group. The corresponding figures were 32%, 74% and 92%, respectively, for the epirubicin group. Time to recurrence differed significantly between two treatment groups (P = 0.0004). Multiplicity increased the risk of recurrence, while grading influenced recurrence, progression and disease specific survival.Conclusions: Bacillus Calmette-Guerin prolonged time to recurrence when compared with epirubicin. Grading was shown to be a universal prognostic factor for recurrence, progression and disease specific survival.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Melbourne, Australia : Blackwell Science Pty
    Nephrology 7 (2002), S. 0 
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
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  • 10
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: SUMMARY:  Cytomegalovirus (CMV) disease is common in postrenal transplant recipients, and may predispose the patients to secondary bacterial or fungal infections. However, simultaneous coinfection is rare and often makes diagnosis difficult. We report a case of CMV pneumonitis in a renal transplant recipient presenting with elevated CMV pp65 antigen level and abnormal chest radiograph. Despite potent and broad-spectrum antimicrobial therapy, his condition deteriorated rapidly – he soon went into respiratory failure, septic shock and died several days later. Transbronchial biopsy and bronchoalveolar lavage obtained before the patient's death showed evidence of invasive pulmonary aspergillosis with concomitant CMV pneumonitis. High index of suspicion and early and empirical initiation of antifungal therapy may be necessary for successful management of fulminant pneumonia in solid organ transplant recipients.
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