Augmentation of Docetaxel-Induced Cytotoxicity in Human PC-3 Androgen-Independent Prostate Cancer Cells by Combination With Four Natural Apoptosis-Inducing Anticancer Compounds.

Docetaxel (DTX) is the treatment of choice for metastatic castration-resistant prostate cancer. However, developing drug resistance is a significant challenge for achieving effective therapy. This study evaluated the anticancer and synergistic effects on DTX of four natural compounds (calebin A, 3'-hydroxypterostilbene, hispolon, and tetrahydrocurcumin) using PC-3 androgen-resistant human prostate cancer cells. We utilized the CellTiter-Glo® luminescent cell viability assay and human PC-3 androgen-independent prostate cancer cells to determine the antiproliferative effects of the four compounds alone and combined with DTX. Cytotoxicity to normal human prostate epithelial cells was tested in parallel using normal immortalized human prostate epithelial cells (RWPE-1). We used cell imaging and quantitative caspase-3 activity to determine whether these compounds induce apoptosis. We also measured the capacity of each drug to inhibit TNF-α-induced NF-kB using a colorimetric assay. Our results showed that all four natural compounds significantly augmented the toxicity of DTX to androgen-resistant PC-3 prostate cancer cells at IC50. Interestingly, when used alone, each of the four compounds had a higher cytotoxic activity to PC-3 than DTX. Mechanistically, these compounds induced apoptosis, which we confirmed by cell imaging and caspase-3 colorimetric assays. Further, when used either alone or combined with DTX, the four test compounds inhibited TNF-α-induced NF-kB production. More significantly, the cytotoxic effects on normal immortalized human prostate epithelial cells were minimal and non-significant, suggesting prostate cancer-specific effects. In conclusion, the combination of DTX with the four test compounds could effectively enhance the anti-prostate cancer activity of DTX. This combination has the added value of reducing the DTX effective concentration. We surmise that calebin A, 3'-hydroxypterostilbene, hispolon, and tetrahydrocurcumin were all excellent drug candidates that produced significant antiproliferative activity when used alone and synergistically enhanced the anticancer effect of DTX. Further in vivo studies using animal models of prostate cancer are needed to confirm our in vitro findings.

N-acetyl cysteine can blunt metabolic and cardiovascular effects via down-regulation of cardiotrophin-1 in rat model of fructose-induced metabolic syndrome.

In this study, we investigated the ability of N-acetyl cysteine (NAC) to alleviate the metabolic disorders in fructose-induced metabolic syndrome (MS) in male rats and to examine its protective effect on aortic and cardiac tissues via its influence on cardiotrophin-1 (CT-1) expression. NAC (20 mg/kg b.w./day) was administered to fructose induced MS animals for 12 weeks. Chronic fructose consumption (20% w/v) increased body weight gain, relative heart weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), insulin resistance (IR), and associated with metabolic alterations. Histological and immunohistochemical examination revealed aortic stiffness and myocardial degeneration and fibrosis together with increased CT-1 expression. Treatment with NAC improved IR, SBP, DBP, and mitigated dyslipidaemia and oxidative stress. Additionally, NAC down-regulated CT-1 expression in the heart and aorta. These findings demonstrated the protective effect of NAC against aortic and myocardial degeneration and fibrosis through down-regulation of CT-1 in fructose induced MS animal model.

Is it the time to implement the routine use of distress thermometer among Egyptian patients with newly diagnosed cancer?

BACKGROUND: The distress thermometer (DT) is an effective tool for identifying distress among cancer patients worldwide. However, DT has not been studied in Egyptian patients. We aimed to study the prevalence of distress among Egyptian patients with different types of cancers using DT. METHODS: A total of 550 patients with newly diagnosed hematological and solid cancers who were followed up at 3 Oncology Centers in Egypt were enrolled. They completed a sociodemographic and clinical status questionnaire, the DT and the Problem List (PL) scale. RESULTS: At a DT cut-off score of ≥4, 46% of patients had significant distress, which was related to the tumor site and stage. The most frequent problems reported were treatment decision (64.4%), worry (47%), and fears (44.5%). In univariate logistic regression analysis, participants who had significant distress described 23 out of 36 problems in the practical, family, emotional, and physical areas. After adjustment to sociodemographic and clinical characteristics, multivariable analysis confirmed that insurance, depression, fear, sadness, worry, loss of interest in usual activity, and sleep were independent factors associated with significant distress in cancer patients. CONCLUSIONS: Almost half of Egyptian patients newly diagnosed with cancer reported significant distress. Those who had significant distress described extra problems in the practical, family, emotional, and physical areas. We recommend the routine use of DT for screening Egyptian patients with cancer, as well as the involvement of the psycho-oncology and social services, at the time of their initial diagnosis.

Serum Procalcitonin in Patients With Combined Lung Cancer and Idiopathic Pulmonary Fibrosis (LC-IPF).

Background Procalcitonin (PCT) is a potential biomarker for sepsis and acts as a guide to antibiotic administration. Previous studies showed that lung cancer (LC) may increase serum PCT levels. However, no studies addressed serum PCT in patients with combined LC and idiopathic pulmonary fibrosis (IPF): LC-IPF. We aimed to evaluate the significance of serum PCT in patients with LC-IPF. Methods A total of 137 patients with IPF who had complete follow-up data were reviewed. They were categorized into two groups: 30 patients with LC and IPF (LC-IPF) and 82 patients with IPF only (IPF). PCT assays in the two groups were done using the enzyme-linked immunosorbent assay (ELISA) technique. Results Median serum PCT (IQR) was significantly higher in patients with LC-IPF in comparison to those with IPF only (0.655± 3.60 vs 0.07 ± 0.11 ng/ml, p=0.016), respectively. LC-IPF patients with neuroendocrine (NE) component, stage IV disease, and with >2 metastatic sites had a significantly higher PCT in comparison to those with non-NE, stages I-III, and <2 metastatic sites, respectively. The presence of the NE component was the only independent risk factor predictive for PCT positivity in patients with LC-IPF; OR1.8 (95% confidence interval (CI) 0.042-2.145; p = 0.042). Conclusion Patients with LC-IPF have higher serum PCT levels than those with IPF alone. These levels are related to the presence of NE component, advanced cancer stage, and the presence of multiple metastases. The presence of the NE component is the only independent risk factor predictive for PCT positivity in patients with LC-IPF. Further studies are warranted.

Is COVID-19 Similar in Pregnant and Non-Pregnant Women?

Approximately one-third of infected pregnant women died from severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) epidemics of the past two decades. It is logical to predict that pregnant women infected with the novel coronavirus (SARS-CoV-2) might be at higher risk for severe illness, morbidity, or mortality compared with non-pregnant women. However, a review of the literature indicates that pregnant women are not more likely to be seriously ill than other healthy non-pregnant women if they develop coronavirus disease (COVID-19). This observation begs the question: "Why does pregnancy not increase the risk for acquiring SARS-CoV-2 infection, nor does it worsen the clinical course of COVID-19 compared with non-pregnant individuals?" Herein, we try to explain our observations when considering whether the immunologic changes of pregnancy and other physiologic adaptations of pregnancy affect the virulence and course of SARS-CoV-2 infection.

Effect of single and repeated administration of amitriptyline on neuropathic pain model in rats: Focus on glutamatergic and upstream nitrergic systems.

AIMS: Few studies have compared the interaction of single and repeated administration of amitriptyline (amit) with the nitrergic system and glutamatergic system in the experimental model of neuropathic pain. We aimed to evaluate the antinociceptive effect of single and repeated administration of amit and to assess whether glutamate preceded inducible nitric oxide synthase (iNOS) inhibition as a mechanism of the analgesic effect of amit in the neuropathic model of pain. MATERIALS AND METHODS: Male Wistar rats were subjected to left sciatic nerve ligation. The effect of single (25 mg kg-1) and repeated (10 mg kg-1 daily for 3 weeks) administration of amit intraperitoneally (i.p.) alone or in combination with aminoguanidine (AG i.p., 100 mg kg-1 for 3 days, a selective iNOS inhibitor) and MK-801 (0.05 mg kg-1 i.p., NMDA antagonist) on resting paw posture and mechanical hyperalgesia were studied. Glutamate level and iNOS protein expression in hippocampus were detected. KEY FINDINGS: Single and repeated administration of amit alone or in combination with AG or MK-801 demonstrated a significant decrease in resting pain score and increase in the pain threshold. Both glutamate and nitrite levels decreased in the hippocampi of single and repeated amit + MK-801 groups. Immunohistochemistry showed a marked decrease in iNOS immunoreactivity in rats treated with single and repeated amit + MK-801. SIGNIFICANCE: Our results suggest that glutamate-dependent mechanisms are involved in the analgesic responses to amit administration. Importantly, glutamatergic system and its upstream nitrergic system play an important role in the antinociceptive action of amit.