Effect of Duration of Symptoms on Orchiectomy Rates in Testicular Torsion in Patients Under 25: Important Prognostic Trends

The purpose of this study is to explore the relationship between duration of symptoms in testicular torsion and the effect on orchiectomy rates, with the intention of establishing an updated timeline for clinical management and surgical urgency

Growth inhibition of androgen-responsive prostate cancer cells with brefeldin A targeting cell cycle and androgen receptor

<p>Abstract</p> <p>Background</p> <p>Androgen ablation is one of the viable therapeutic options for patients with primary hormone (androgen)-dependent prostate cancer. However, an antibiotic brefeldin A (BFA) has been shown to exhibit the growth inhibitory effect on human cancer cells. We thus investigated if BFA might inhibit proliferation of androgen-responsive prostate cancer LNCaP cells and also explored how it would be carried out, focusing on cell cycle and androgen receptor (AR).</p> <p>Methods</p> <p>Androgen-mediated cellular events in LNCaP cells were induced using 5α-dihydrotestosterone (DHT) as an androgenic mediator. Effects of BFA on non-DHT-stimulated or DHT-stimulated cell growth were assessed. Its growth inhibitory mechanism(s) was further explored; performing cell cycle analysis on a flow cytometer, assessing AR activity by AR binding assay, and analyzing AR protein expression using Western blot analysis.</p> <p>Results</p> <p>DHT (1 nM) was capable of stimulating LNCaP cell growth by ~40% greater than non-stimulated controls, whereas BFA (30 ng/ml) completely inhibited such DHT-stimulated proliferation. Cell cycle analysis showed that this BFA-induced growth inhibition was associated with a ~75% reduction in the cell number in the S phase and a concomitant increase in the G₁cell number, indicating a G₁cell cycle arrest. This was further confirmed by the modulations of specific cell cycle regulators (CDK2, CDK4, cyclin D₁, and p21^WAF1), revealed by Western blots. In addition, the growth inhibition induced by BFA was accompanied by a profound (~90%) loss in AR activity, which would be presumably attributed to the significantly reduced cellular AR protein level.</p> <p>Conclusions</p> <p>This study demonstrates that BFA has a potent growth inhibitory activity, capable of completely inhibiting DHT (androgen)-stimulated LNCaP proliferation. Such inhibitory action of BFA appears to target cell cycle and AR: BFA led to a G₁cell cycle arrest and the down-regulation of AR activity/expression, possibly accounting for its primary growth inhibitory mechanism. Thus, it is conceivable that BFA may provide a more effective therapeutic modality for patients with hormone-dependent prostate cancer.</p

Possible immunotherapeutic potentiation with D-Fraction in prostate cancer cells

<p>Abstract</p> <p>Background</p> <p>Prostate cancer remains the most common malignancy among elderly men and the second leading cause of cancer death in the United States. Although several conventional therapies are currently available, they have a low efficacy and the more effective treatment modalities need to be established. Interferons (IFNs) are one of such options known as immunotherapy and demonstrated their antitumor effects on certain cancer types. Yet such antitumor activity should be improved or potentiated to have the satisfactory outcomes. In fact, <it>combination </it>therapy has been proposed as an alternative approach and is being underway in human and animal studies. Accordingly, we studied whether the combination of IFN-α and D-fraction (PDF), a bioactive mushroom extract, might potentiate anticancer activity of IFN-α in prostate cancer PC-3 cells <it>in vitro</it>.</p> <p>Results</p> <p>Potential effects of recombinant IFN-α_2b(0–100,000 IU/ml), PDF (0���1,000 μg/ml), or their combinations were assessed on the growth of PC-3 cells at 72 h. Cell cycle analysis using a flow cytometer and Western blot analysis were performed to explore antiproliferative mechanism of these agents. The dose-dependent study showed that IFN-α_2bup to 20,000 (20 K) IU/ml had no significant effects, but >60% growth reduction was attained ≤50 K IU/ml. Similarly, PDF showed no effects up to 250 μg/ml but ~65% growth reduction was seen at 1,000 μg/ml. When IFN-α_2band PDF were combined, a relatively low concentration (10 K IU/ml) of IFN-α_2band PDF (250 μg/ml) resulted in a ~65% growth reduction. This was accompanied by a G₁cell cycle arrest, indicated by cell cycle analysis. Western blots also revealed that the G₁-specific cell cycle regulators, CDK2, CDK4, CDK6, cyclin D₁, and cyclin E, had been significantly (>60%) down-regulated in IFN/PDF-treated cells.</p> <p>Conclusion</p> <p>The combination of IFN-α_2b(10 K IU/ml) and PDF (250 μg/ml) is capable of inducing a ~65% reduction in PC-3 cell growth. This appears to be due to a synergistic potentiation of two agents, leading to a G₁cell cycle arrest. Thus, it is conceivable that PDF may potentiate IFN-α_2bactivity, improving immunotherapy for prostate cancer.</p

Chemosensitizing effect of maitake mushroom extract on carmustine cytotoxicity in human bladder cancer cells

Background: Despite several therapeutic options available for bladder cancer, the outcomes are less satisfactory.  To find a more effective modality, we were interested in the bioactive mushroom extract, PDF, which has been shown to sensitize certain anticancer drugs.  Accordingly, we investigated if cytotoxic effects of several anticancer drugs used on bladder cancer patients could be enhanced with PDF in vitro.Methods: Human bladder cancer T24 cells were treated with four anticancer drugs, carmustine (BCNU), 5-fluorouracil (5FU), cisplatin (CPL), and doxorubicin (DOX) alone, their combinations, or in combination with PDF, and cell viability was determined.  To explore the anticancer mechanism, the status of glyoxalase I (Gly-I), an enzyme involved in the drug resistance of cancer cells, and oxidative stress that can cause severe cellular injury/damage was also assessed.Results: BCNU and 5FU alone resulted in a >50% reduction in cell viability but CPL and DOX had no such effects.  Only a combination of BCNU and PDF led to a drastic (~90%) cell viability reduction, accompanied by inactivation of Gly-I and an increase in oxidative stress.  However, any combinations of other drugs and PDF had little effects on cell viability, Gly-I activity, or severity of oxidative stress.Conclusions: This study shows that anticancer activity of BCNU is significantly potentiated with PDF in T24 cells.  This is rather attributed to inactivated Gly-I and increased oxidative stress.  Therefore, PDF appears to have a chemosensitizing effect capable of enhancing BCNU cytotoxicity, which may offer an alternative, improved therapeutic option for bladder cancer

Comparison of weighted and unweighted methods of wealth indices for assessing SOCIO-ECONOMIC status

Due to some of the limitations of monetary measures, various non-monetary approaches for assessing household wealth have been developed as alternative tools for classifying household socio-economic status. Among them, wealth indices based on household durable assets are being used. The literature revealed that two basic methods of constructing wealth indices are employed: an unweighted method, where assets are weighted equally; and a weighted method, where specific weights are assigned to assets. In the case of using the weighted method, weighting can be assigned using various techniques. The overall objective of the study is to compare the wealth indices constructed by using weighted and unweighted methods for assessing the socio-economic status of households in rural Bangladesh. Firstly, the study attempts to construct wealth indices based on durable assets using the unweighted method and two techniques of the weighted method: weighted index using the inverse of proportion, and weighted index using principal component analysis (PCA). Following this, the study compares some distributional characteristics of these indices as well as monetary indicators. At the same time, the study evaluates and examines some attractive properties of these indices such as the extent of clumping and truncation, consistency with traditional monetary measures. Comparative analysis revealed that the unweighted asset index, as well as weighted asset index using PCA, can be treated as an efficient alternative to the monetary measures to evaluate the living standard of the households in the present study. However, due to some advantage\u27s asset index using PCA can be considered to be somewhat better than the unweighted index. But, as the unweighted asset index is not very different from the weighted asset index using PCA, it can also be used as an alternative to the monetary measures without the need to use weighting