Increased generation of reactive oxygen species (ROS) and an altered redox status have long been observed in cancer cells, and recent studies suggest that this biochemical property of cancer cells can be exploited for therapeutic benefits. Cancer cells in advanced stage tumours frequently exhibit multiple genetic alterations and high oxidative stress, suggesting that it might be possible to preferentially eliminate these cells by pharmacological ROS insults. However, the upregulation of antioxidant capacity in adaptation to intrinsic oxidative stress in cancer cells can confer drug resistance. Abrogation of such drug-resistant mechanisms by redox modulation could have significant therapeutic implications. We argue that modulating the unique redox regulatory mechanisms of cancer cells might be an effective strategy to eliminate these cells.

Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach?

Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life. Despite the lower bioavailability, therapeutic efficacy of...

Bioavailability of curcumin: problems and promises.

Curcumin (diferuloylmethane) is a polyphenol derived from the plant Curcuma longa, commonly called turmeric. Extensive research over the last 50 years has indicated this polyphenol can both prevent and treat cancer. The anticancer potential of curcumin stems from its ability to suppress proliferation of a wide variety of tumor cells, down-regulate transcription factors NF- κB, AP-1 and Egr-1; down-regulate the expression of COX2, LOX, NOS, MMP-9, uPA, TNF, chemokines, cell surface adhesion molecules and cyclin D1; down-regulate growth factor receptors (such as EGFR and HER2); and inhibit the activity of c-Jun N-terminal kinase, protein tyrosine kinases and protein serine/threonine kinases. In several systems, curcumin has been described as a potent antioxidant and anti-inflammatory agent. Evidence has also been presented to suggest that curcumin can suppress tumor initiation, promotion and metastasis. Pharmacologically, curcumin has been found to be safe. Human clinical trials indicated no dose-limiting toxicity when administered at doses up to 10 g/day. All of these studies suggest that curcumin has enormous potential in the prevention and therapy of cancer. The current review describes in detail the data supporting these studies. Curcumin, derived from turmeric (vernacular name: Haldi), is a rhizome of the plant Curcuma longa. The medicinal use of this plant has been documented in Ayurveda (the Indian

Anticancer potential of curcumin: preclinical and clinical studies.

https://alzheimer.neurology.ucla.edu/pubs/YangJBCcurc2005.pdf

Curcumin Inhibits Formation of Amyloid β Oligomers and Fibrils, Binds Plaques, and Reduces Amyloid in Vivo

The use of herbal medicinal products and supplements has increased tremendously over the past three decades with not less than 80% of people worldwide relying on them for some part of primary health care. Although therapies involving these agents have shown promising potential with the efficacy of a good number of herbal products clearly established, many of them remain untested and their use are either poorly monitored or not even monitored at all. The consequence of this is an inadequate knowledge of their mode of action, potential adverse reactions, contraindications and interactions with existing orthodox pharmaceuticals and functional foods to promote both safe and rational use of these agents. Since safety continues to be a major issue with the use of herbal remedies, it becomes imperative, therefore, that relevant regulatory authorities put in place appropriate measures to protect public health by ensuring that all herbal medicines are safe and of suitable quality. This review discusses toxicity related-issues and major safety concerns arising from the use of herbal medicinal products and also highlights some important challenges associated with effective monitoring of their safety.

/pdf/the-growing-use-of-herbal-medicines-issues-relating-to-1ckeueyb3l.pdf

The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety

Role of urinary cytology and urinary deoxyribonucleic acid flow cytometry in the diagnosis of bladder cancer.

To evaluate the oncological 
outcomes and complications of patients with saturated prostate cryoablation. A cohort of 208 patients cumulatively treated between June 2008 and December 2012 qualified for study inclusion, each undergoing total-gland cryoablation for prostate cancer. The degree of saturated prostate cryoablation was defined as the average prostate volume per cryoprobe (APVC), and divided into four groups (groups 1–4: <3 ml, 3 to <4 ml, 4 to <5 ml, ≧5 ml, respectively). Post-ablative complications were measured prospectively at weeks 1, 2, 4, 8, 12, and 24 by using the Common Terminology Criteria for Adverse Events. Biochemical failure was gauged by Phoenix criterion. The Kruskal–Wallis rank sum test and Chi-square test were used to compare clinical characteristics of therapeutic subsets. The Cox proportional hazard model was applied for comparison of recurrence risk between groups. APVC group 1 had the highest pre-operative PSA value and smallest prostate size among the groups. Multivariate analysis of risks of biochemical failures revealed that the larger the APVC, the higher the hazard (p for trend = 0.01). Compared to the group 1 patients, the hazard ratios of biochemical failures in groups 2–4 were 4.4 (confidence interval (CI): 0.5–37), 8.8 (CI 1.1–73), and 9.4 (CI 1.1–78), respectively. Nevertheless, the complication rate of APVC group 1 patients was similar to the other three groups. Saturated prostate cryoablation by reducing APVC would be beneficial for cancer control without compromising patient safety.

Prognostic value of saturated prostate cryoablation for localized prostate cancer.

The present invention is correlated with a derivative of 18β-glycyrrhetinic acid apt to suppressing cancer cells, which is selected from a group comprising of structure I and structure II: wherein residue R1 is selected from one of CH3 and CH2C6H5, residue R2 is selected from one of COOCH3, COOCH2CH3, COOCH(CH3)2, CONHCH2CH3, CONHCH2CH2CH3, and CONHCH2(CH3)2, and residue R3 is selected from one of COOCH2CH3, COOCH(CH3)2, CONHCH2CH3, CONHCH2CH2CH3, and CONHCH2(CH3)2.

DERIVATIVE OF 18beta-GLYCYRRHETINIC ACID APT TO SUPPRESS CANCER CELLS

Analysis of transrectal and suprapubic ultrasonography for prostate size evaluation

Enzalutamide significantly improved clinical outcomes compared with placebo in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) with disease progression despite androgen deprivation therapy (ADT) in the PREVAIL study. However, few patients from Asia were enrolled. Our study (NCT02294461) aimed to evaluate the safety and efficacy of enzalutamide in this disease setting in patients in mainland China, Korea, Taiwan, and Hong Kong.In this double-blind, phase III study, patients with asymptomatic/mildly symptomatic metastatic prostate cancer and disease progression despite ADT were randomized to enzalutamide (160 mg/day) or placebo. The primary endpoint was time to prostate-specific antigen (PSA) progression. Secondary endpoints included overall survival, radiographic progression-free survival, time to first skeletal-related event (SRE), time to initiation of cytotoxic chemotherapy, PSA response ≥ 50%, best overall soft-tissue response, and safety. Pre-planned interim analysis was scheduled following approximately 175 PSA-progression events (67% of targeted total of 261 events). An additional 5-year landmark analysis of overall survival, time to antineoplastic therapy, and safety was performed.The double-blind study period was stopped after interim analysis owing to the benefit of enzalutamide over placebo. Overall, 388 patients were randomized (enzalutamide, n = 198; placebo, n = 190). Baseline characteristics were balanced between treatment groups. Enzalutamide significantly reduced risk of PSA progression vs placebo (hazard ratio 0.38; 95% CI 0.27-0.52; P < 0.0001). Median time to PSA progression was 8.31 months with enzalutamide and 2.86 months with placebo. Secondary endpoints, including 5-year overall survival, were significantly improved with enzalutamide, except time to first SRE. Adverse-event incidence was similar between enzalutamide and placebo. Fatigue was the most common drug-related adverse event in both treatment groups.Enzalutamide significantly reduced risk of PSA progression, improved secondary efficacy endpoints, and was well tolerated in chemotherapy-naïve Asian patients with mCRPC with disease progression despite ADT.www.gov NCT02294461. 

/pdf/enzalutamide-in-chemotherapy-naive-metastatic-castration-3axsrln6.pdf

Yeong-Shiau Pu

Papers

Role of urinary cytology and urinary deoxyribonucleic acid flow cytometry in the diagnosis of bladder cancer.

Prognostic value of saturated prostate cryoablation for localized prostate cancer.

DERIVATIVE OF 18beta-GLYCYRRHETINIC ACID APT TO SUPPRESS CANCER CELLS

Analysis of transrectal and suprapubic ultrasonography for prostate size evaluation

Enzalutamide in Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer: An Asian Multiregional, Randomized Study