scholarly journals Quercetin as a Novel Therapeutic Approach for Lymphoma

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Saiedeh Razi Soofiyani ◽  
Kamran Hosseini ◽  
Haleh Forouhandeh ◽  
Tohid Ghasemnejad ◽  
Vahideh Tarhriz ◽  
...  
Keyword(s):  
Clinical Studies ◽  
Hodgkin’S Lymphoma ◽  
Experimental Studies ◽  
Hodgkin's Lymphoma ◽  
In Vivo Studies ◽  
Therapeutic Effects ◽  
Malignant Diseases ◽  
Antitumor Effects

Lymphoma is a name for malignant diseases of the lymphatic system including Hodgkin’s lymphoma and non-Hodgkin’s lymphoma. Although several approaches are used for the treatment of these diseases, some of them are not successful and have serious adverse effects. Therefore, other effective treatment methods might be interesting. Studies have indicated that plant ingredients play a key role in treating several diseases. Some plants have already shown a potential therapeutic effect on many malignant diseases. Quercetin is a flavonoid found in different plants and could be useful in the treatment of different malignant diseases. Quercetin has its antimalignant effects through targeting main survival pathways activated in tumor cells. In vitro/in vivo experimental studies have demonstrated that quercetin possesses a cytotoxic effect on lymphoid cancer cells. Regardless of the optimum results that have been obtained from both in vitro/in vivo studies, few clinical studies have analyzed the antitumor effects of quercetin in lymphoid cancers. Thus, it seems that more clinical studies should introduce quercetin as a therapeutic, alone or in combination with other chemotherapy agents. Here, in this study, we reviewed the anticancer effects of quercetin and highlighted the potential therapeutic effects of quercetin in various types of lymphoma.

scholarly journals Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2506
Author(s):  
Wamidh H. Talib ◽  
Ahmad Riyad Alsayed ◽  
Alaa Abuawad ◽  
Safa Daoud ◽  
Asma Ismail Mahmod
Keyword(s):  
Clinical Trials ◽  
Current Knowledge ◽  
Biological Activities ◽  
Experimental Studies ◽  
Therapeutic Effects ◽  
Cell Proliferation Inhibition ◽  
Different Types ◽  
Solid Foundation

Melatonin is a pleotropic molecule with numerous biological activities. Epidemiological and experimental studies have documented that melatonin could inhibit different types of cancer in vitro and in vivo. Results showed the involvement of melatonin in different anticancer mechanisms including apoptosis induction, cell proliferation inhibition, reduction in tumor growth and metastases, reduction in the side effects associated with chemotherapy and radiotherapy, decreasing drug resistance in cancer therapy, and augmentation of the therapeutic effects of conventional anticancer therapies. Clinical trials revealed that melatonin is an effective adjuvant drug to all conventional therapies. This review summarized melatonin biosynthesis, availability from natural sources, metabolism, bioavailability, anticancer mechanisms of melatonin, its use in clinical trials, and pharmaceutical formulation. Studies discussed in this review will provide a solid foundation for researchers and physicians to design and develop new therapies to treat and prevent cancer using melatonin.

scholarly journals Essential Oils as Treatment Strategy for Alzheimerʼs Disease: Current and Future Perspectives

Planta Medica ◽  
2018 ◽  
Vol 85 (03) ◽  
pp. 239-248 ◽  
Author(s):  
Anju Benny ◽  
Jaya Thomas
Keyword(s):  
Essential Oils ◽  
Clinical Studies ◽  
Symptomatic Relief ◽  
Memory Loss ◽  
Clinical Trial Data ◽  
In Vivo Studies ◽  
Scientific Databases ◽  
Preclinical And Clinical Studies

AbstractAlzheimerʼs disease is a multifarious neurodegenerative disease that causes cognitive impairment and gradual memory loss. Several hypotheses have been put forward to postulate its pathophysiology. Currently, few drugs are available for the management of Alzheimerʼs disease and the treatment provides only symptomatic relief. Our aim is to review the relevant in vitro, in vivo, and clinical studies focused toward the potential uses of essential oils in the treatment of Alzheimerʼs disease. Scientific databases such as PubMed, ScienceDirect, Scopus, and Google Scholar from April 1998 to June 2018 were explored to collect data. We have conducted wide search on various essential oils used in different models of Alzheimerʼs disease. Out of 55 essential oils identified for Alzheimerʼs intervention, 28 have been included in the present review. A short description of in vivo studies of 13 essential oils together with clinical trial data of Salvia officinalis, Salvia lavandulifolia, Melissa officinalis, Lavandula angustifolia, and Rosmarinus officinalis have been highlighted. In vitro studies of remaining essential oils that possess antioxidant and anticholinesterase potential are also mentioned. Our literary survey revealed encouraging results regarding the various essential oils being studied in preclinical and clinical studies of Alzheimerʼs disease with significant effects in modulating the pathology through anti-amyloid, antioxidants, anticholinesterase, and memory-enhancement activity.

Viscum album (L) extracts in cancer treatment: a systematic review of in vitro and in vivo studies

2021 ◽  
Vol 14 (2) ◽  
pp. 52-52
Author(s):  
Aloisio Cunha de Carvalho ◽  
Leoni Villano Bonamin
Keyword(s):  
Systematic Review ◽  
Experimental Studies ◽  
Pharmaceutical Preparations ◽  
Viscum Album ◽  
In Vitro Models ◽  
In Vivo Studies ◽  
Pubmed Database ◽  
Anti Cancer

Background: Several reviews about phytotherapy and homeopathy have been published in the last years, including Viscum album (VA.L). VA is a parasite plant whose extract has anti-cancer proprieties and is used alone or in combination with conventional chemotherapy. Methods: We performed a systematic review about the in vivo and in vitro models described in the literature, including veterinary clinical trials. The literature was consulted from Pubmed database. Results: There are several kinds of pharmaceutical preparations about VA and their active principles used in experimental studies, lectin being frequently studied (alone or as an extract compound). More than 50% of available literature about VA is related to the lectin effects. On the other hand, the effects of viscotoxins are less studied. Among the in vivo experimental studies about VA and its compounds, the B16 murine melanoma is the most used model, followed by Ehrlich, Walker and Dalton tumors. The results point to the apoptotic effects, metastasis control and tumor regression. Some veterinary clinical studies about the use of VA in the treatment of sarcoid, fibrosarcoma and neuroblastoma are quoted in literature too, with interesting results. Considering the in vitro models, our review revealed that NALM6 leukemia cells, B16 melanoma and NC1-H460 lung carcinoma were the most studied tumor models, apoptosis signals being the most important findings. Only one study verified immunoglobulin and interleukin production. All consulted papers were related to phytotherapy preparations only. Conclusions: Although the literature about the anti-cancer activity of VA extract and its lectins is enough, there is a marked lack of information about viscotoxin activities and about the effects of homeopathic preparations of this plant on animal tumors and on in vitro cultivated tumor cells.

A Bispecific Diabody That Mediates Natural Killer Cell Cytotoxicity Against Xenotransplantated Human Hodgkin’s Tumors

Blood ◽  
1999 ◽  
Vol 94 (8) ◽  
pp. 2562-2568 ◽  
Author(s):  
Michaela A.E. Arndt ◽  
Jürgen Krauss ◽  
Sergey M. Kipriyanov ◽  
Michael Pfreundschuh ◽  
Melvyn Little
Keyword(s):  
Natural Killer ◽  
Hodgkin’S Lymphoma ◽  
Bispecific Antibody ◽  
Killer Cell ◽  
Hodgkin's Lymphoma ◽  
Natural Killer Cell Cytotoxicity ◽  
Variable Domains ◽  
Bispecific Diabody

CD16/CD30 bispecific monoclonal antibodies can induce remissions of Hodgkin’s disease refractory to chemo- and radiotherapy. However, the development of human antimouse immunoglobulin antibodies and allergic reactions precludes repeated applications of the antibody. Moreover, problems of producing and purifying sufficient amounts of material limit the clinical practicability of this novel treatment approach. To overcome these obstacles, we have constructed a bispecific antibody in a diabody form that only employs the variable domains of the CD16/CD30 hybrid hybridoma. The diabody compared favorably with the parent CD16/CD30 bispecific antibody in its ability to activate and target natural killer cells in vitro. Its administration to mice bearing xenografted Hodgkin’s lymphoma resulted in a marked regression of tumor growth, thus proving for the first time the capability of a diabody for immune recruitment in vivo. The CD16/CD30 diabody is a novel reagent that should considerably facilitate the immunotherapy of patients with refractory Hodgkin’s lymphoma.

scholarly journals How Harmful Is Particulate Matter Emitted from Biomass Burning? A Thailand Perspective

2019 ◽  
Vol 5 (4) ◽  
pp. 353-377 ◽  
Author(s):  
Helinor J. Johnston ◽  
William Mueller ◽  
Susanne Steinle ◽  
Sotiris Vardoulakis ◽  
Kraichat Tantrakarnapa ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Health Effects ◽  
Biomass Burning ◽  
Large Body ◽  
Experimental Studies ◽  
In Vivo Studies ◽  
Indoor And Outdoor Environments ◽  
Epidemiology Studies

Abstract Purpose of Review A large body of epidemiological evidence demonstrates that exposure to particulate matter (PM) is associated with increased morbidity and mortality. Many epidemiology studies have investigated the health effects of PM in Europe and North America and focussed on traffic derived PM. However, elevated levels of PM are a global problem and the impacts of other sources of PM on health should be assessed. Biomass burning can increase PM levels in urban and rural indoor and outdoor environments in developed and developing countries. We aim to identify whether the health effects of traffic and biomass burning derived PM are similar by performing a narrative literature review. We focus on Thailand as haze episodes from agricultural biomass burning can substantially increase PM levels. Recent Findings Existing epidemiology, in vitro and in vivo studies suggest that biomass burning derived PM elicits toxicity via stimulation of oxidative stress, inflammation and genotoxicity. Thus, it is likely to cause similar adverse health outcomes to traffic PM, which causes toxicity via similar mechanisms. However, there is conflicting evidence regarding whether traffic or biomass burning derived PM is most hazardous. Also, there is evidence that PM released from different biomass sources varies in its toxic potency. Summary We recommend that epidemiology studies are performed in Thailand to better understand the impacts of PM emitted from specific biomass sources (e.g. agricultural burning). Further, experimental studies should assess the toxicity of PM emitted from more diverse biomass sources. This will fill knowledge gaps and inform evidence-based interventions that protect human health.

scholarly journals Crocetin Extracted from Saffron Shows Antitumor Effects in Models of Human Glioblastoma

2020 ◽  
Vol 21 (2) ◽  
pp. 423 ◽  
Author(s):  
Alessandro Colapietro ◽  
Andrea Mancini ◽  
Flora Vitale ◽  
Stefano Martellucci ◽  
Adriano Angelucci ◽  
...  
Keyword(s):  
Wound Repair ◽  
Fatty Acid Synthase ◽  
Disease Free Survival ◽  
In Vivo Studies ◽  
Comparable Efficacy ◽  
Antitumor Effects ◽  
Radio Therapy ◽  
U87 Cells

Over recent years, many authors discussed the effects of different natural compounds on glioblastoma (GBM). Due to its capacity to impair survival and progression of different cancer types, saffron extract (SE), named crocetin (CCT), is particularly noteworthy. In this work, we elucidated the antitumor properties of crocetin in glioma in vivo and in vitro models for the first time. The in vitro results showed that the four tumor cell lines observed in this study (U251, U87, U138, and U373), which were treated with increasing doses of crocetin, showed antiproliferative and pro-differentiative effects as demonstrated by a significant reduction in the number of viable cells, deep changes in cell morphology, and the modulation of mesenchymal and neuronal markers. Indeed, crocetin decreased the expression of Cluster of Differentiation CD44, CD90, CXCR4, and OCT3/4 mesenchymal markers, but increased the expression of βIII-Tubulin and neurofilaments (NFH) neuronal linage-related markers. Epigenetic mechanisms may modulate these changes, since Histone Deacetylase, HDAC1 and HDAC3 were downmodulated in U251 and U87 cells, whereas HDAC1 expression was downmodulated in U138 and U373 cells. Western blotting analyses of Fatty Acid Synthase, FASN, and CD44 resulted in effective inhibition of these markers after CCT treatment, which was associated with important activation of the apoptosis program and reduced glioma cell movement and wound repair. The in vivo studies aligned with the results obtained in vitro. Indeed, crocetin was demonstrated to inhibit the growth of U251 and U87 cells that were subcutaneously injected into animal models. In particular, the Tumor To Progression or TTP values and Kaplan–Meier curves indicated that crocetin had more major effects than radiotherapy alone, but similar effects to temozolomide (TMZ). An intra-brain cell inoculation of a small number of luciferase-transfected U251 cells provided a model that was able to recapitulate recurrence after surgical tumor removal. The results obtained from the orthotopic intra-brain model indicated that CCT treatment increased the disease-free survival (DFS) and overall survival (OS) rates, inducing a delay in appearance of a detectable bioluminescent lesion. CCT showed greater efficacy than Radio Therapy (RT) but comparable efficacy to temozolomide in xenograft models. Therefore, we aimed to continue the study of crocetin’s effects in glioma disease, focusing our attention on the radiosensitizing properties of the natural compound and highlighting the ways in which this was realized.

scholarly journals Prosopis Plant Chemical Composition and Pharmacological Attributes: Targeting Clinical Studies from Preclinical Evidence

Biomolecules ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 777 ◽  
Author(s):  
Javad Sharifi-Rad ◽  
Farzad Kobarfard ◽  
Athar Ata ◽  
Seyed Abdulmajid Ayatollahi ◽  
Nafiseh Khosravi-Dehaghi ◽  
...  
Keyword(s):  
Chemical Composition ◽  
Clinical Studies ◽  
Positive Impact ◽  
Biological Effects ◽  
Food Supplement ◽  
In Vivo Studies ◽  
Plant Chemical ◽  
Food Applications

Members of the Prosopis genus are native to America, Africa and Asia, and have long been used in traditional medicine. The Prosopis species most commonly used for medicinal purposes are P. africana, P. alba, P. cineraria, P. farcta, P. glandulosa, P. juliflora, P. nigra, P. ruscifolia and P. spicigera, which are highly effective in asthma, birth/postpartum pains, callouses, conjunctivitis, diabetes, diarrhea, expectorant, fever, flu, lactation, liver infection, malaria, otitis, pains, pediculosis, rheumatism, scabies, skin inflammations, spasm, stomach ache, bladder and pancreas stone removal. Flour, syrup, and beverages from Prosopis pods have also been potentially used for foods and food supplement formulation in many regions of the world. In addition, various in vitro and in vivo studies have revealed interesting antiplasmodial, antipyretic, anti-inflammatory, antimicrobial, anticancer, antidiabetic and wound healing effects. The phytochemical composition of Prosopis plants, namely their content of C-glycosyl flavones (such as schaftoside, isoschaftoside, vicenin II, vitexin and isovitexin) has been increasingly correlated with the observed biological effects. Thus, given the literature reports, Prosopis plants have positive impact on the human diet and general health. In this sense, the present review provides an in-depth overview of the literature data regarding Prosopis plants’ chemical composition, pharmacological and food applications, covering from pre-clinical data to upcoming clinical studies.

Construction and Characterization of a Novel Ribonuclease Immunotoxin Consisting of Two Ranpirnase (Rap) Molecules Fused to an Internalizing Anti-CD74 Humanized IgG4 Antibody.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3289-3289
Author(s):  
Sailaja S. Vanama ◽  
Puja Sapra ◽  
Hans J. Hansen ◽  
Ivan D. Horak ◽  
David M. Goldenberg ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Xenograft Model ◽  
Hodgkin's Lymphoma ◽  
Light Chains ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Sds Page

Abstract Ranpirnase (Rap), isolated from frog (Rana pipiens) oocytes, is a monomeric ribonuclease (MW 11800) that kills cells by degrading t-RNA upon internalization. Previous studies indicated that the cytotoxicity of Rap could be enhanced more than 10,000-fold when the enzyme is chemically conjugated to an internalizing antibody. Here we describe the construction and characterization of 2L-Rap-hLL1-γ4P, composed of two Rap molecules fused to hLL1, an internalizing anti-CD74 humanized monoclonal antibody. To reduce unwanted cytotoxicity, the IgG1 constant region of hLL1 was replaced with an IgG4 that contains a proline mutation in the hinge region. The Rap gene was inserted at the N-terminus of the light chain in the expression vector of hLL1 and expressed in NS0 mouse myeloma cells. The fusion protein was characterized by a variety of techniques, including SE-HPLC, SDS-PAGE, in vitro transcription translation (IVTT) assay using luciferase reporter system, and competition ELISA to measure the binding affinity for CD74. The in vitro potency was determined in non-Hodgkin’s lymphoma (Daudi) and multiple myeloma (MC/CAR) cell lines by MTS tetrazolium dye reduction assay. In vivo pharmacokinetics and biodistribution of radiolabeled 2L-Rap-hLL1- γ4P was compared to radiolabeled hLL1 mAb in naïve mice and in vivo therapeutic efficacy of 2L-Rap-hLL1- γ4P was determined in a xenograft model of Burkitt’s non-Hodgkin’s lymphoma (Daudi). Purified 2L-Rap-hLL1- γ4P was shown to be a single peak by SE-HPLC and its MW determined by MALDI-TOF to be 177,150, which is in agreement with the MW of one IgG (150,000) plus two Rap molecules (24,000). Reducing-SDS-PAGE of 2L-Rap-hLL1- γ4P revealed the presence of 3 bands, one corresponding to the heavy chain and the other two appearing to be derived from the Rap-fused light chains (38,526 and 36,700 by MS). Occurrence of the 2 light chains was shown to be due to glycosylation of Rap at the N69 residue. The binding affinity of 2L-Rap-hLL1- γ4P for CD74 was indistinguishable from that of hLL1. Both 2L-Rap-hLL1- γ4P and hLL1 bound to CD74 with subnanomolar affinity. The EC50 of RNase activity, as measured by the IVTT assay, was 300 pM for 2L-Rap-hLL1- γ4P and 30 pM for recombinant Rap (expressed in E. coil). In in vitro cytotoxicity assays, 2L-Rap-hLL1- γ4P was significantly cytotoxic against Daudi (EC50 280 pM) and the myeloma cell line, MC/CAR (EC50 50 nM). In contrast, free Rap or naked hLL1 did not demonstrate significant cytotoxicity at the concentrations tested. In vivo, the pharmacokinetic profile of 2L-Rap-hLL1- γ4P was almost identical to that of naked hLL1. Both 2L-Rap-hLL1- γ4P and hLL1 showed biphasic clearance from the circulation; the α and β half-life (t1/2) of 2L-Rap-hLL1- γ4P were 5 h and 119 h, respectively, and those of hLL1 were 4 h and 125 h, respectively. In tissue biodistribution studies, no significant difference was observed between 2L-Rap-hLL1- γ4P and hLL1 with regards to normal tissue uptake. Early efficacy results in the Daudi Burkitt’s non-Hodgkin’s lymphoma xenograft model demonstrate that treatment with a single dose of 2L-Rap-hLL1- γ4P as low as 1 μg/mouse significantly improves survival in comparison to untreated control mice (P<0.0001).

Synthetic 15-mer Peptide (PCK3145) Derived from Prostate Secretory Protein with In Vitro and In Vivo Activity Against Non-Hodgkin’s Lymphoma and Other Hematologic Malignancies.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1388-1388
Author(s):  
Mireille Guerin ◽  
Cynthia Therien ◽  
Gorazd Krosl ◽  
Jinzi J. Wu ◽  
Helene Dulude ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Tumour Growth ◽  
Hematologic Malignancies ◽  
Secretory Protein ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Anti Tumor Activity

Abstract Prostate secretory protein 94 (PSP-94) has been shown to exert anti-tumor activity against prostate cancer cells, particularly in the form of PCK3145, a synthetic peptide corresponding to amino acids 31–45 of PSP-94. Indeed, when tested in a murine model, this peptide could reduce experimental prostate tumour growth. In addition, when evaluated in a Phase I clinical study, this peptide demonstrated a particularly interesting safety profile, with almost complete lack of toxicity. In order to determine whether PCK3145 could exert cytotoxic activity against other marrow infiltrating cancers, we tested its activity both in vitro and in vivo against non-Hodgkin’s lymphoma (NHL) and other hematologic cancers. Interestingly, PCK3145 inhibited the proliferation of human NHL (SR) and myeloma (RPMI-8226) cell lines in vitro. To explore its anti-tumor activity in vivo, the impact of PCK3145 was also measured by inoculating P815 malignant cells into syngeneic DBA mice. First, four groups of 6 DBA mice were injected subcutaneously with 2x104 P815 cells and then treated with subcutaneous injections of PCK3145, and compared to a peptide with the scrambled amino acid sequence, PCK5266 (peptide derived from amino acids 52 to 66 of PSP-94), and phosphate-buffered saline (PBS). Treatment with PCK3145 significantly decreased the growth of P815 tumours in comparison to PBS (p<0.001), scrambled peptide (p<0.05) and PCK5266 (p<0.01), confirming in vivo anti-tumor activity and suggesting that tumour growth inhibition is due to the specific amino acid sequence of PCK3145. The same model was used to determine the effect of PCK3145 on metastatic dissemination following intraperitoneal administration of the peptide. PCK3145 treatment led to a decreased number of liver metastasis compared to PBS (p<0.05) and scrambled peptide (p<0.05) controls. In order to determine whether PCK3145 exerted its activity by altering metalloproteinase release, metalloproteinase MMP-9 levels were measured 3 weeks post-tumor cell exposure. MMP-9 levels, measured by ELISA, in the peripheral blood of treated P815 bearing mice were similar to those obtained with healthy animals (12.83±1.890 (mean±SD) ng/ml and 7.183±0.4070 ng/ml, respectively), while MMP-9 levels were elevated in mice treated with PBS and scrambled peptide (35.12±8.559 ng/ml and 22.60±3.944 ng/ml, respectively; p<0.05). We next tested PCK3145 treatment on human SR lymphoma cell line grown subcutaneously in NOD/SCID mice. Similarly to results obtained with murine tumors, treatment with PKC3145 resulted in significant inhibition of SR non-Hodgkin’s lymphoma growth compared to treatment with PBS (p<0.001) and scrambled peptide (p<0.01). These results demonstrate that in vivo treatment with PCK3145 can reduce tumor cell proliferation of both murine and human hematologic cancers. In addition, PCK3145 has the potential to inhibit tumor cells dissemination by lowering MMP-9 secretion. Thus, PCK3145 represents a unique peptide demonstrating sequence-specific anti-tumor activity against NHL and other hematologic malignancies. Based on these results, clinical studies are being designed to evaluate its therapeutic activity in humans.

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