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

ABSTRACT: 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.

SUBMITTER: Keizman D

PROVIDER: S-EPMC8706421 | biostudies-literature |

REPOSITORIES: biostudies-literature

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

Project description: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.

| S-EPMC10459199 | biostudies-literature

Galectin-3 Inhibition With Modified Citrus Pectin in Hypertension.

Project description:We investigated the effect of galectin-3 (Gal-3) inhibition with modified citrus pectin on markers of collagen metabolism in a proof-of-concept randomized placebo-controlled trial of participants with elevated Gal-3 levels and hypertension. Although higher Gal-3 levels were associated with female sex, diabetes, and reduced glomerular filtration rate in cross-sectional analyses, treatment with modified citrus pectin did not change collagen markers. The effect of Gal-3 inhibition among individuals with heart failure warrants further investigation.

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

Project description: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-? (TNF-?) 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-? 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.

| S-EPMC5576403 | biostudies-literature

Citrus pectin modified by microfluidization and ultrasonication: Improved emulsifying and encapsulation properties.

Project description:In this study, modified citrus pectin treated with a combination of microfluidization and ultrasonication was compared to the original and ultrasonication treated pectin on hydrodynamic diameter, molecular weight, polydispersity, zeta potential, apparent viscosity, Fourier-transform infrared spectroscopy (FTIR), 2,2-diphenyl-1-picryl hydrazyl (DPPH) radical scavenging capacity, scanning electron microscope (SEM), atomic force microscopy (AFM), their emulsifying properties and encapsulation properties. Modified pectin treated with a combination of microfluidization and moderate ultrasonication (MUB) was found to have lowest hydrodynamic diameter (418 nm), molecular weight (237.69 kDa) and polydispersity (0.12), and relatively low apparent viscosity among all pectin samples. Furthermore, it showed significantly higher DPPH radical scavenging capacity than the original pectin although only slightly higher than that of ultrasonication treated one (UB). MUB showed a thin fibrous morphology and decreased degree of branching from SEM and AFM. Emulsion stabilized by MUB had highest centrifugal and thermal stability compared to emulsions stabilized by UB and the original pectin. This could be attributed to higher interfacial loading of MUB (17.90 mg/m2) forming more compact interfacial layer observed by confocal laser scanning microscopy (CLSM). Moreover, both MUB and UB exhibited improved encapsulation functionality to protect cholecalciferol (vitamin D3) from UV degradation compared to the original pectin.

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Prospective Comparison of F-18 Choline PET/CT Scan Versus Axial MRI for Detecting Bone Metastasis in Biochemically Relapsed Prostate Cancer Patients.

Project description:We compared fluor-18 choline positron emission tomography/computed tomography (PET/CT) and axial skeleton magnetic resonance imaging (MRI) prospectively obtained for the detection of bone metastases in non-castrated patients with biochemically recurrent prostate cancer following primary treatment. PET/CT was performed 45 min post-injection of 3-4 MBq/kg F-18 methyl choline. MRI included T1- and fluid sensitive T2-weighted images of the spine and pelvis. Readers were initially blinded from other results and all scans underwent independent double reading. The best valuable comparator (BVC) defined the metastatic status. On the basis of the BVC, 15 out of 64 patients presented with 24 bone metastases. On a patient level, the sensitivity and specificity of MRI and PET were not significantly different. On a lesion level, the sensitivity of MRI was significantly better compared to PET, and the specificity did not differ significantly. In conclusion, axial MRI is an interesting screening tool for the detection of bone metastases because of its low probability of false negative results. However, F-18 choline PET is a valuable addition as it can overrule false positive MRI results and detect non-axial metastases.

| S-EPMC5745392 | biostudies-literature

Purification, chemical analysis and inhibitory effects on galectin-3 of enzymatic pH-modified citrus pectin.

Project description:Modified citrus pectin (MCP), a commercially available dietary supplement prepared from citrus pectin, contains several different polysaccharide domains, but its primary chemical structure and the binding epitopes that antagonize galectin-3 function remain unclear. In this study, five fractions were isolated from MCP after endo-polygalacturonase degradation (EMCP) and a combination of DEAE-cellulose and Sepharose CL-6B or Sephadex G-75 chromatography. Their primary structures, abilities to inhibit galectin-3-mediated hemagglutination, and antiproliferation activities on MCF-7 and A549 cell lines were studied. Results showed that EMCP-3p, one of the five fractions, was composed of Glc (89.8%), Gal (3.8%), Ara (3.1%), GalA (1.1%), Man (0.9%), and Rha (1.3%) with an average molecular weight of 88.4 KDa, which had the most substantial degree of galectin-3 inhibition with an MIC of 31.25 μg/mL, and it exhibited remarkable cytotoxicity against MCF-7 (36.7%) and A549 (57.4%) cell lines. These results provide new insight into the structure-function relationships of EMCP-derived polysaccharides.

| S-EPMC8628203 | biostudies-literature

Phase II Trial of Acai Juice Product in Biochemically Recurrent Prostate Cancer.

Project description:BACKGROUND:Plant derivatives have been studied as therapies for prostate cancer based on their purported anti-inflammatory and antioxidant properties and low toxicities. The acai berry is an example of a plant rich in phytochemicals, which may slow the growth of prostate cancer. METHODS:This was a phase II, Simon 2-stage clinical trial in patients with biochemically recurrent prostate cancer with a primary endpoint of prostate-specific antigen (PSA) response. Patients were asymptomatic, with a rising PSA of at least 0.2 ng/mL, and were treated with twice daily intake of Acai Juice Product until PSA progression, with a primary endpoint of PSA response. RESULTS:Twenty-one patients were enrolled in the first stage of the trial. One of those patients had a PSA response within the study time period. The PSA doubling time was lengthened in 71% of patients (95% confidence interval = 48% to 89%) on the trial, and in a small number of responders, this was sustained over an extended time. CONCLUSIONS:This study did not meet its primary endpoint of 50% PSA response. Nevertheless, the overall tolerability and effects on PSA stabilization warrant further exploration in a biochemically recurrent population.

| S-EPMC6247557 | biostudies-literature

Heat-modified citrus pectin induces apoptosis-like cell death and autophagy in HepG2 and A549 cancer cells.

Project description:Cancer is still one of the leading causes of death worldwide, and finding new treatments remains a major challenge. Previous studies showed that modified forms of pectin, a complex polysaccharide present in the primary plant cell wall, possess anticancer properties. Nevertheless, the mechanism of action of modified pectin and the pathways involved are unclear. Here, we show that citrus pectin modified by heat treatment induced cell death in HepG2 and A549 cells. The induced cell death differs from classical apoptosis because no DNA cleavage was observed. In addition, Z-VAD-fmk, a pan-caspase inhibitor, did not influence the observed cell death in HepG2 cells but appeared to be partly protective in A549 cells, indicating that heat-modified citrus pectin might induce caspase-independent cell death. An increase in the abundance of the phosphatidylethanolamine-conjugated Light Chain 3 (LC3) protein and a decrease in p62 protein abundance were observed in both cell types when incubated in the presence of heat-modified citrus pectin. These results indicate the activation of autophagy. To our knowledge, this is the first time that autophagy has been revealed in cells incubated in the presence of a modified form of pectin. This autophagy activation appears to be protective, at least for A549 cells, because its inhibition with 3-methyladenine increased the observed modified pectin-induced cytotoxicity. This study confirms the potential of modified pectin to improve chemotherapeutic cancer treatments.

| S-EPMC4368604 | biostudies-literature

PSMA- and GRPR-Targeted PET: Results from 50 Patients with Biochemically Recurrent Prostate Cancer.

Project description:Novel radiopharmaceuticals for PET are being evaluated for the diagnosis of biochemical recurrence (BCR) of prostate cancer (PC). We compared the gastrin-releasing peptide receptor-targeting 68Ga-RM2 with the prostate-specific membrane antigen (PSMA)-targeting 68Ga-PSMA11 and 18F-DCFPyL. Methods: Fifty patients underwent both 68Ga-RM2 PET/MRI and 68Ga-PSMA11 (n = 23) or 18F-DCFPyL (n = 27) PET/CT at an interval ranging from 1 to 60 d (mean ± SD, 15.8 ± 17.7 d). SUVmax was collected for all lesions. Results: 68Ga-RM2 PET was positive in 35 and negative in 15 of the 50 patients. 68Ga-PSMA11/18F-DCFPyL PET was positive in 37 and negative in 13 of the 50 patients. Both scans detected 70 lesions in 32 patients. Forty-three lesions in 18 patients were identified on only 1 scan: 68Ga-RM2 detected 7 more lesions in 4 patients, whereas 68Ga-PSMA11/18F-DCFPyL detected 36 more lesions in 13 patients. Conclusion: 68Ga-RM2 remains a valuable radiopharmaceutical even when compared with the more widely used 68Ga-PSMA11/18F-DCFPyL in the evaluation of BCR of PC. Larger studies are needed to verify that identifying patients for whom these 2 classes of radiopharmaceuticals are complementary may ultimately allow for personalized medicine.

| S-EPMC8612333 | biostudies-literature

Migration and proliferation of cancer cells in culture are differentially affected by molecular size of modified citrus pectin.

Project description:While chemically and thermally modified citrus pectin (MCP) has already been studied for health benefits, it is unknown how size-fractionated oligo- and polysaccharides differentially affect cancer cell behavior. We produced thermally MCP and fractionated it by molecular size to evaluate the effect these polymers have on cancer cells. MCP30/10 (between 30 and 10?kDa) had more esterified homogalacturonans (HG) and fewer rhamnogalacturonans (RG-I) than MCP and MCP30 (higher than 30?kDa), while MCP10/3 (between 10 and 3?kDa) showed higher amounts of type I arabinogalactans (AGI) and lower amounts of RG-I. MCP3 (smaller than 3?kDa) presented less esterified HG and the lowest amount of AGI and RG-I. Our data indicate that the enrichment of de-esterified HG oligomers and the AGI and RG-I depletions in MCP3, or the increase of AGI and loss of RGI in MCP30/10, enhance the anticancer behaviors by inhibiting migration, aggregation, and proliferation of cancer cells.

| S-EPMC6886127 | biostudies-literature

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