Modified Citrus Pectin Treatment in Non-Metastatic Biochemically Relapsed Prostate Cancer: Long-Term Results of a Prospective Phase II Study.

The optimal therapy for patients with non-metastatic biochemically relapsed prostate cancer (BRPC-M0) after local therapy is elusive. Thus, the evaluation of new non-toxic compounds in BRPC-M0 patients is warranted. PectaSol®-Modified citrus pectin (P-MCP) is a food supplement categorized as GRAS (Generally Recognized As Safe) by the FDA. It is a competitive inhibitor of the galectin-3 protein, which is involved in cancer pathogenesis. In an early report of the present phase 2 study, P-MCP treatment for 6 months led to prostate-specific antigen doubling time (PSADT) improvement in 75% of patients with BRPC-M0. Herein, we report the second long-term treatment phase of an additional 12 months of P-MCP therapy (4.8 g × 3/day orally) in patients without disease progression after the initial 6 months of therapy. Of the 46 patients that entered the second treatment phase, 7 patients withdrew consent and decided to continue therapy out of pocket, and 39 initiated the second treatment phase. After a total of 18 months of P-MCP treatment, 85% (n = 33) had a durable long-term response, with 62% (n = 24) showing decreased/stable PSA, 90% (n = 35) PSADT improvement, and all with negative scans. No patient had grade 3/4 toxicity. In conclusion, P-MCP may have long-term durable efficacy and is safe in BRPC-M0.

The potential roles of galectin-3 in AKI and CKD.

Acute kidney injury (AKI) is a common condition with high morbidity and mortality, and is associated with the development and progression of chronic kidney disease (CKD). The beta-galactoside binding protein galectin-3 (Gal3), with its proinflammatory and profibrotic properties, has been implicated in the development of both AKI and CKD. Serum Gal3 levels are elevated in patients with AKI and CKD, and elevated Gal3 is associated with progression of CKD. In addition, Gal3 is associated with the incidence of AKI among critically ill patients, and blocking Gal3 in murine models of sepsis and ischemia-reperfusion injury results in significantly lower AKI incidence and mortality. Here we review the role of Gal3 in the pathophysiology of AKI and CKD, as well as the therapeutic potential of targeting Gal3.

Modified Citrus Pectin Treatment in Non-Metastatic Biochemically Relapsed Prostate Cancer: Results of a Prospective Phase II Study.

Optimal therapy of biochemically relapsed prostate cancer (BRPC) after local treatment is elusive. An established modified citrus pectin (PectaSol®, P-MCP), a dietary polysaccharide, is an established antagonist of galectin-3, a carbohydrate-binding protein involved in cancer pathogenesis. Based on PSA dynamics, we report on the safety and the primary outcome analysis of a prospective phase II study of P-MCP in non-metastatic BRPC based. Sixty patients were enrolled, and one patient withdrew after a month. Patients (n = 59) were given P-MCP, 4.8 grams X 3/day, for six months. The primary endpoint was the rate without PSA progression and improved PSA doubling time (PSADT). Secondary endpoints were the rate without radiologic progression and toxicity. Patients that did not progress by PSA and radiologically at six months continued for an additional twelve months. After six months, 78% (n = 46) responded to therapy, with a decreased/stable PSA in 58% (n = 34), or improvement of PSADT in 75% (n = 44), and with negative scans, and entered the second twelve months treatment phase. Median PSADT improved significantly (p = 0.003). Disease progression during the first 6 months was noted in only 22% (n = 13), with PSA progression in 17% (n = 10), and PSA and radiologic progression in 5% (n = 3). No patients developed grade 3 or 4 toxicity.

A translational study of Galectin-3 as an early biomarker and potential therapeutic target for ischemic-reperfusion induced acute kidney injury.

PURPOSE: We evaluated Galectin-3 (Gal-3) as a potential early biomarker of acute kidney disease (AKI), and the effect of Gal-3 inhibition by modified citrus pectin (P-MCP) on renal ischemia/reperfusion (I/R) induced AKI. METHODS: Among fifty-two post-cardiac surgery patients, serum and urine Gal-3 levels were examined on intensive care unit (ICU) admission. In a rat renal I/R injury model, Gal-3 levels, renal function, and histopathology were evaluated in rats pretreated with P-MCP for one week (n = 16) compared to controls (n = 16). RESULTS: Among post-cardiac surgery patients, median serum and urine Gal-3 levels on ICU admission were higher in patients who developed AKI than those who did not (AKI vs non-AKI serum: 18.37 vs. 8.08 ng/ml, p < 0.001; AKI vs non-AKI urine:13.27 vs. 6.27 ng/ml, p < 0.001). Serum and urine Gal-3 levels were reliable biomarkers for detecting AKI (AUC: 0.88 and 0.87). In the rat renal I/R injury model, I/R caused an increase of Gal-3 at 0.5 h after reperfusion (p < 0.05). Gal-3 inhibition by P-MCP significantly decreased Gal-3 release and expression (p < 0.05), reduced interleukin (IL-6) release (p < 0.05), decreased renal dysfunction, and reduced renal tubular injury. CONCLUSIONS: Gal-3 is a potential early biomarker in the diagnosis of AKI. Inhibition of Gal-3 may provide therapeutic utility in the treatment of I/R-induced AKI.

Galectin-3 in septic acute kidney injury: a translational study.

BACKGROUND: Galectin-3 (Gal-3) is a pleiotropic glycan-binding protein shown to be involved in sepsis and acute kidney injury (AKI). However, its role has never been elucidated in sepsis-associated AKI (S-AKI). We aimed to explore Gal-3's role and its potential utility as a therapeutic target in S-AKI. METHODS: In 57 patients admitted to the intensive care unit (ICU) with sepsis, serum Gal-3 was examined as a predictor of ICU mortality and development of AKI. In a rat model of S-AKI induced by cecal ligation and puncture (CLP), 7-day mortality and serum Gal-3, Interleukin-6 (IL-6), and creatinine were examined at 2, 8, and 24 hours (h) post-CLP. Two experimental groups received the Gal-3 inhibitor modified citrus pectin (P-MCP) at 400 mg/kg/day and 1200 mg/kg/day, while the control group received water only (n = 18 in each group). RESULTS: Among 57 patients, 27 developed AKI and 8 died in the ICU. Serum Gal-3 was an independent predictor of AKI (OR = 1.2 [95% CI 1.1-1.4], p = 0.01) and ICU mortality (OR = 1.4 [95% CI 1.1-2.2], p = 0.04) before and after controlling for age, AKI, and acute physiology and chronic health evaluation (APACHE II) score. In the CLP rat experiment, serum Gal-3 peaked earlier than IL-6. Serum Gal-3 was significantly lower in both P-MCP groups compared to control at 2 h post-CLP (400 mg: p = 0.003; 1200 mg: p = 0.002), and IL-6 was significantly lower in both P-MCP groups at all time points with a maximum difference at 24 h post-CLP (400 mg: p = 0.015; 1200 mg: p = 0.02). In the Gal-3 inhibitor groups, 7-day mortality was significantly reduced from 61% in the control group to 28% (400 mg P-MCP: p = 0.03) and 22% (1200 mg P-MCP: p = 0.001). Rates of AKI per RIFLE criteria were significantly reduced from 89% in the control group to 44% in both P-MCP groups (400 mg: p = 0.007; 1200 mg: p = 0.007). CONCLUSIONS: This translational study demonstrates the importance of Gal-3 in the pathogenesis of S-AKI, and its potential utility as a therapeutic target.

Establishing low-density lipoprotein apheresis tolerability in patients with prior anaphylactoid reactions to lipoprotein apheresis using magnesium sulfate.

BACKGROUND: Lipoprotein apheresis (LA) tolerability is a key factor for the utilization of this therapy. Common reactions to LA are hypotension and nausea. Serious reactions include severe hypotension and anaphylactoid reactions (0.13%-1.3% and 0.2%-0.4%, respectively). The bradykinin response drives these reactions and can worsen with the use of angiotensin-converting-enzyme inhibitors. Efforts to mitigate these reactions are necessary for the tolerability of LA with a dextran sulfate-adsorption (DSA) system. MATERIALS AND METHODS: In an effort to increase apheresis tolerability, seven patients at The University of Kansas, Department of Clinical Pharmacology, who had prior anaphylactoid reactions (defined as general cutaneous flushing, nausea/vomiting, tongue swelling, lightheadedness, and hypotension) to the DSA despite pharmacologic intervention, were treated with pre-LA intravenous magnesium adapted from a protocol developed by co-author Eliaz. This protocol consists of 1.5 g of magnesium sulfate administered over 45 minutes. All seven patients were treated with intravenous magnesium sulfate immediately before LA. RESULTS: No episodes of anaphylactoid reactions during LA have been reported to date. CONCLUSIONS: Magnesium infusion before DSA can be utilized to establish tolerability in patients with prior anaphylactoid reactions to LA. Proposed mechanisms include temporary stabilization of the negative-positive interactions of the dextran sulfate filter leading to a reduction of circulating bradykinin, reduction of nitric oxide, and reduction of the sympathetic response to LA.

Intravenous Honokiol in Drug-Resistant Cancer: Two Case Reports.

Context: Long-term patient survival in cancer is affected by drug resistance. Honokiol (HNK) is a small-molecule polyphenol isolated from the bark and seed cones of Magnolia officinalis. HNK has been shown to enhance the effects of chemotherapy and inhibit drug resistance in preclinical models. HNK was well tolerated in multiple animal models when administered orally, intravenously (IV), and via intraperitoneal route. However, there are limited human data on the use of HNK in general, and specifically via IV (HNK-IV) in cancer. Objective: We aim to assess the efficacy, safety, and tolerability of HNK-IV in patients with drug-resistant tumors. Methods: This is a case study of 2 cancer patients who utilized HNK-IV as part of their cancer treatment regimen. The initial infusion of HNK was 10 mg/kg body weight, and subsequent treatments were increased up to 50 mg/kg according to individual tolerance, over 2 weeks. Results: Positive clinical response was achieved in both patients, including improved symptoms and quality of life. No serious adverse side effects occurred, and there were no adverse effects on laboratory parameters (complete blood count, kidney, and liver function). Transient sedation and minor nausea were noted and resolved postinfusion. Conclusions: This is the first report of HNK-IV in human patients. Given the positive clinical results, safety, and tolerability, the use of HNK-IV warrants further investigation regarding optimum formulation, and its use as adjunctive therapy in cancer patients.

Pleiotropic Effects of Modified Citrus Pectin.

Modified citrus pectin (MCP) has a low-molecular-weight degree of esterification to allow absorption from the small intestinal epithelium into the circulation. MCP produces pleiotropic effects, including but not limited to its antagonism of galectin-3, which have shown benefit in preclinical and clinical models. Regarding cancer, MCP modulates several rate-limiting steps of the metastatic cascade. MCP can also affect cancer cell resistance to chemotherapy. Regarding fibrotic diseases, MCP modulates many of the steps involved in the pathogenesis of aortic stenosis. MCP also reduces fibrosis to the kidney, liver, and adipose tissue. Other benefits of MCP include detoxification and improved immune function. This review summarizes the pleiotropic effects of MCP.

Modified Citrus Pectin / Alginate Dietary Supplement Increased Fecal Excretion of Uranium: A Family.

CONTEXT: Uranium is found in geological deposits around the world. Toxicology of uranium includes nephrotoxicity, carcinogenicity, genotoxicity, diminished bone growth, and developmental defects. Mining and agricultural practices have escalated the regional exposure. OBJECTIVE: A family of six living in the Phoenix, AZ area had concerns about uranium exposure. For intervention, a dietary supplement of modified citrus pectin: sodium alginate (2:1) was recommended based on research supporting abilities to lower heavy metal toxicity. METHODS: Baseline urine and fecal samples were analyzed using inductively coupled plasma mass spectrometry. The supplement was self-administered at 3 capsules (750 mg/capsule) twice daily. Samples were taken at baseline, 6-days, and 6-weeks, additional fecal samples before stopping supplement and then after a 6-week washout period. Home water system was tested as well for heavy metals. RESULTS: Urine showed no detectable uranium whereas feces had significant change at 6-days, which persisted at 6-weeks. After a post-treatment period of 6-weeks, a decrease in excretion was seen in 5 of the 6 subjects. Home water showed cautionary levels of uranium. CONCLUSION: The supplement promoted fecal excretion of what is likely ongoing low-level exposure via ingestion. This is the first report of a supplement promoting uranium excretion suggesting it may reduce negative health effects in regions where chronic uranium exposure is known.

Modified Citrus Pectin as a Potential Sensitizer for Radiotherapy in Prostate Cancer.

BACKGROUND: Radiotherapy is one of the primary therapies for localized prostatic carcinoma. Therefore, there is an emerging need to sensitize prostatic cancer cells to chemotherapy/radiotherapy. Modified citrus pectin (MCP) is an effective inhibitor of galectin-3 (Gal-3), which is correlated with tumor progression, proliferation, angiogenesis, and apoptosis. PURPOSE: This study was directed to evaluate the efficacy of combining ionizing radiation (IR) with MCP on PCa cells. STUDY DESIGN: Effects of treatments on PCa cells survival were evaluated using XTT assay, flow cytometry, and clonogenic survival assay. Expression of selected proteins was estimated using western blotting. Cell motility, migration, and invasion were determined. Contribution of reactive oxygen species production to treatment effects on cell viability was tested. RESULTS: Radiotherapy combined with MCP reduced viability and enhanced radiosensitivity associated with a decrease in Gal-3, cleavage of the precursor of caspase-3, increased expression of the pro-apoptotic protein Bax, and downregulation of DNA repair pathways, poly-ADP-ribose polymerase, and proliferating cell nuclear antigen. MCP significantly reduced the invasive and migratory potential of PCa cells. Combining sodium pyruvate with MCP and IR mitigated the effect on cell viability. CONCLUSION: Our findings demonstrated that MCP sensitized PCa cells to IR by downregulating anti-apoptotic Gal-3, modulating DNA repair pathways, and increasing ROS production. For the first time the correlation between MCP, radiotherapy, and Gal-3 for prostatic cancer treatment was found. In addition, MCP reduced the metastatic properties of PCa cells. These findings provide MCP as a radiosensitizing agent to enhance IR cytotoxicity, overcome radioresistance, and reduce clinical IR dose.

The effects of galectin-3 depletion apheresis on induced skin inflammation in a porcine model.

Galectin-3 (Gal-3), a ß-galactoside-binding lectin that is expressed in mammalian cells, is known to modulate several biological functions such as cell-cell adhesion, macrophage activation, angiogenesis, metastasis, and fibrosis. The goal of this study was to evaluate the ability of Gal-3 depletion apheresis using an adsorption column with immobilized anti-Gal-3-antibody to reduce inflammation induced by Complete Freund's Adjuvant injection in a skin inflammation porcine model. Here, we report that plasma perfusion by apheresis through a Gal-3 binding immuno-affinity column reduces plasma Gal-3 levels to below limits of quantitative detection, and results in significant decrease in skin inflammation, including degree and duration of inflammatory lesions. Human plasma was tested ex vivo and found to be efficiently depleted using the anti-Gal-3 affinity column. This study demonstrates the potential of Gal-3 depletion apheresis as a therapeutic method for inflammation-mediated disease, supporting continued research in this area for clinical application.

Improvements in Self-reported Lower Urinary Tract Symptoms With Prostate Health Supplement.

Context: Benign prostatic hyperplasia (BPH) produces lower urinary tract symptoms (LUTS) that diminish quality of life. Conventional treatments are often accompanied by adverse side effects. By contrast, consumers of phytochemicals-based dietary supplements often report a reduction in symptoms without side effects. The field needs studies that quantify the strength and character of perceived benefits. Objectives: The study intended to quantify the character and strength of perceived improvements in LUTS in men, after the consumption of a prostate health supplement. Design: The research team sent questionnaires to 200 potential participants, requesting their self-reported retrospective assessments of their LUTS for the month prior to starting their use of a prostate health supplement, ProstaCaid (ie, at baseline from memory), and their assessments at the time of the study (ie, postintervention) based on their current symptoms. Setting: The study was conducted from consumers of ProstaCaid at their home through a mailed questionnaire from Econugenics (Santa Rosa, CA, USA). Participants: Participants were 65 male patients, ages 56 to 86 y, including those diagnosed with BPH, prostate cancer, or multiple diagnoses, or who had no formal diagnosis. Interventions: Participants had taken at least 2 capsules/d of the supplement for a minimum of 2 mo. Outcome Measures: Participants were asked to recall and rate urinary tract symptoms: (1) incomplete emptying (ie, sensation of not emptying the bladder), (2) urinary frequency, (3) intermittency, (4) urgency, (5) weak stream, (6) straining, and (7) nocturia, (ie, how many times the participant typically gets up at night to urinate). A questionnaire based on the international prostate symptom score questionnaire was used. Logistic regressions, based on the proportional odds ratios of LUTS scores, were used for statistical analysis. Results: The participants reported substantial improvements in a range of individual and composite LUTS scores. In addition, the variability of current scores was substantially reduced compared with recalled, past scores, indicating that the perceived improvements were shared among the respondents. Statistical analysis identified urgency and weak stream as the symptoms showing the greatest reduction in perceived severity, which therefore could be used as the subject of future case-controlled studies. Conclusions: When properly interpreted, retrospective, self-reported data can yield insights into the perceived benefits of supplements and help guide the care of patients who augment traditional treatment with alternative medicines. Reported improvements can also guide the development of testable hypotheses for randomized, case-controlled studies.

Synergistic Antioxidant and Anti-Inflammatory Effects between Modified Citrus Pectin and Honokiol.

Inflammation is a normal physiological process; however, dysregulation of this process may contribute to inflammatory-based chronic disorders and diseases in animals and humans. Therefore, the antioxidant and anti-inflammatory properties of natural products, often recognized in traditional medicine systems, represent therapeutic modalities to reduce or prevent uncontrolled inflammatory processes which in turn potentially ameliorate or prevent sequelae of inflammatory-based symptoms of chronic diseases. We have investigated the antioxidant and anti-inflammatory effects of honokiol (HNK) and modified citrus pectin (MCP) in vitro and examined whether the MCP : HNK combination has synergistic effects on antioxidant and anti-inflammatory properties. Although both HNK and MCP induced a dose-dependent increase in antioxidant activity, the latter has a consistently higher antioxidant effect. The MCP : HNK (9 : 1) combination induced a synergistic effect on antioxidant activity suggesting that the combination is significantly more efficacious than individual compounds. In mouse monocytes, the lipopolysaccharide- (LPS-) induced tumor necrosis-α (TNF-α) synthesis was significantly inhibited by HNK and the MCP : HNK combination in a dose-dependent manner and synergistic effects were clearly demonstrated with the combination on TNF-α inhibition. This combination effect was also evident on inhibition of nuclear factor-kappa B activity, cyclooxygenase-II activity, and lipid peroxidation in mouse monocytes. Further research into the combination is warranted.

BreastDefend enhances effect of tamoxifen in estrogen receptor-positive human breast cancer in vitro and in vivo.

BACKGROUND: Tamoxifen (TAM) has been widely used for the treatment of estrogen receptor (ER)-positive breast cancer and its combination with other therapies is being actively investigated as a way to increase efficacy and decrease side effects. Here, we evaluate the therapeutic potential of co-treatment with TAM and BreastDefend (BD), a dietary supplement formula, in ER-positive human breast cancer. METHODS: Cell proliferation and apoptosis were determined in ER-positive human breast cancer cells MCF-7 by MTT assay, quantitation of cytoplasmic histone-associated DNA fragments and expression of cleaved PARP, respectively. The molecular mechanism was identified using RNA microarray analysis and western blotting. Tumor tissues from xenograft mouse model were analyzed by immunohistochemistry. RESULTS: Our data clearly demonstrate that a combination of 4-hydroxytamoxifen (4-OHT) with BD lead to profound inhibition of cell proliferation and induction of apoptosis in MCF-7 cells. This effect is consistent with the regulation of apoptotic and TAM resistant genes at the transcription and translation levels. Importantly, TAM and BD co-treatment significantly enhanced apoptosis, suppressed tumor growth and reduced tumor weight in a xenograft model of human ER-positive breast cancer. CONCLUSION: BD sensitized ER-positive human breast cancer cells to 4-OHT/TAM treatment in vitro and in vivo. BreastDefend can be used in an adjuvant therapy to increase the therapeutic effect of tamoxifen in patients with ER-positive breast cancer.

Methods for the detection and serum depletion of porcine galectin-3.

BACKGROUND: Circulating galectin-3 (Gal-3) is elevated in systemic inflammatory disorders, fibrotic diseases, and in cancers. Gal-3 is a promising cancer target where it promotes tumorigenesis and metastasis, as well as in renal, pulmonary, hepatic, and cardiovascular diseases, because of its role as a driver of fibrotic remodeling. This reports goal was to establish methods for the detection and removal of porcine Gal-3 that will enable further studies of the therapeutic potential of Gal-3 depletion by apheresis in porcine disease models. The long-term aim is to develop a safe, effective method of removing Gal-3 via apheresis as a standalone therapeutic tool and as an adjuvant to other therapies. METHODS: Purified recombinant porcine Gal-3 was prepared and used as the standard for development of a porcine Gal-3 enzyme-linked immunosorbent assay (ELISA). Different affinity column matrices that incorporated either a rat IgG2a anti-Gal-3 monoclonal antibody or carbohydrate ligand were assessed for depletion of Gal-3 from porcine serum. RESULTS: A porcine Gal-3 ELISA with a linear range from 0.3 to 20 ng/mL was able to detect native porcine Gal-3 in both fetal (∼150-200 ng/mL) and juvenile (∼5-15 ng/mL) porcine serum samples. Use of an anti-Gal-3 monoclonal antibody affinity column depleted Gal-3 from porcine serum to at least 313 pg/mL, the limit of ELISA detection. CONCLUSIONS: Methods have been developed for the detection and depletion of porcine Gal-3. These methods will be used to study the specific effects of Gal-3 depletion via apheresis in porcine models of disease.

Honokiol inhibits migration of renal cell carcinoma through activation of RhoA/ROCK/MLC signaling pathway.

Honokiol, a biologically active compound isolated from Magnolia bark, has been shown to possess promising anticancer effect through induction of apoptosis. However, there is a relative lack of information regarding its anti­metastatic activity. Renal cell carcinoma (RCC) is the most common malignancy of the adult kidney and is known for high risk of metastasis. Clinically, therapeutic methods for metastatic RCC cases are limited and efforts to exploit new treatments are still ongoing. The results of our current investigation first revealed that honokiol suppressed the proliferation of different human RCCs without affecting cell viability. In addition, honokiol inhibited migration of highly metastatic RCC 786­0 cells and stimulated the activity of small GTPase, RhoA. Furthermore, phosphorylated myosin light chain (MLC) and excessive formation of actin stress fibers were identified in 786­0 cells treated with honokiol. Interestingly, the pharmacological Rho­associated protein kinase (ROCK) inhibitor Y­27632 attenuated contraction of actin stress fibers induced by honokiol and abrogated honokiol­mediated inhibition of cell migration. Together these important findings suggest that honokiol suppresses the migration of highly metastatic RCC through activation of RhoA/ROCK/MLC signaling and warrants attention in the treatment of RCC metastasis as a novel therapeutic approach.

Lipoprotein apheresis reduces circulating galectin-3 in humans.

BACKGROUND: Plasma galectin-3 (Gal-3) is elevated in, and drives, diverse systemic inflammatory disorders, including cancer, cardiovascular diseases, and diabetes. Circulating Gal-3 promotes tumorigenesis and metastasis, as well as fibrotic remodeling, and is a promising therapeutic target. Apheresis has proven utility in reducing circulating disease-promoting substances, exemplified by the success of lipoprotein apheresis (LA) in abrogating cardiovascular disease progression in drug-refractory hypercholesterolemia patients. We compared the clinical utility of two FDA-approved LA systems in reducing plasma Gal-3 in humans. METHODS: Plasma Gal-3 levels were assessed by ELISA in blinded samples drawn pre- and post-apheresis from hypercholesterolemia patients (n = 10/group) undergoing therapeutic LA using either a heparin-induced extracorporeal LDL precipitation (HELP) or dextran sulfate-adsorption (DSA) system. RESULTS: Mean baseline plasma Gal-3 concentrations (±SD) were 14.3 ± 5.1 (range 6.6-22.8) and 14.5 ± 2.8 (range 10.6-19.8) ng/mL in the HELP and DSA groups, respectively. Post-apheresis Gal-3 levels were respectively reduced by 19.4% and 22.7% in the HELP (P = 0.0094) and DSA (P = 0.0027) systems (paired t-tests); the difference between devices was insignificant (P = 0.5288; Mann-Whitney). Post-treatment Gal-3 levels were 11.3 ± 3.7 (HELP; range 4.5-16.3) and 11.3 ± 3.8 (DSA; range 7.5-20.7) ng/mL. CONCLUSIONS: Circulating Gal-3 levels showed a statistically significant decrease in humans undergoing therapeutic LA. Although absolute Gal-3 reduction was ≈19-23%, this effect, combined with reducing atherogenic LDL and other inflammation mediators (e.g., CRP, fibrinogen, Lp-PLA2 ), may enhance apheresis clinical benefits. Applying new Gal-3-specific extraction technologies to apheresis may be advantageous in treating diverse pathologies that are promoted by elevated plasma Gal-3. J. Clin. Apheresis 31:388-392, 2016. © 2015 Wiley Periodicals, Inc.

Honokiol inhibits bladder tumor growth by suppressing EZH2/miR-143 axis.

The oncoprotein EZH2, as a histone H3K27 methyltransferase, is frequently overexpressed in various cancer types. However, the mechanisms underlying its role in urinary bladder cancer (UBC) cells have not yet fully understood. Herein, we reported that honokiol, a biologically active biphenolic compound isolated from the Magnolia officinalis inhibited human UBC cell proliferation, survival, cancer stemness, migration, and invasion, through downregulation of EZH2 expression level, along with the reductions of MMP9, CD44, Sox2 and the induction of tumor suppressor miR-143. Either EZH2 overexpression or miR-143 inhibition could partially reverse honokiol-induced cell growth arrest and impaired clonogenicity. Importantly, it was first revealed that EZH2 could directly bind to the transcriptional regulatory region of miR-143 and repress its expression. Furthermore, honokiol treatment on T24 tumor xenografts confirmed its anticancer effects in vivo, including suppression tumor growth and tumor stemness, accompanied by the dysregulation of EZH2 and miR-143 expressions. Our data suggest a promising therapeutic option to develop drugs targeting EZH2/miR-143 axis, such as honokiol, for bladder cancer treatment.