scholarly journals Molecular Mechanisms of the Anti-Cancer Effects of Isothiocyanates from Cruciferous Vegetables in Bladder Cancer

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 575 ◽  
Author(s):  
Tomhiro Mastuo ◽  
Yasuyoshi Miyata ◽  
Tsutomu Yuno ◽  
Yuta Mukae ◽  
Asato Otsubo ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Molecular Mechanisms ◽  
Checkpoint Inhibitors ◽  
Treatment Strategies ◽  
Allyl Isothiocyanate ◽  
Cruciferous Vegetables ◽  
Current Trends ◽  
Carcinogenic Potential ◽  
Anti Cancer ◽  
Future Direction

Bladder cancer (BC) is a representative of urological cancer with a high recurrence and metastasis potential. Currently, cisplatin-based chemotherapy and immune checkpoint inhibitors are used as standard therapy in patients with advanced/metastatic BC. However, these therapies often show severe adverse events, and prolongation of survival is unsatisfactory. Therefore, a treatment strategy using natural compounds is of great interest. In this review, we focused on the anti-cancer effects of isothiocyanates (ITCs) derived from cruciferous vegetables, which are widely cultivated and consumed in many regions worldwide. Specifically, we discuss the anti-cancer effects of four ITC compounds—allyl isothiocyanate, benzyl isothiocyanate, sulforaphane, and phenethyl isothiocyanate—in BC; the molecular mechanisms underlying their anti-cancer effects; current trends and future direction of ITC-based treatment strategies; and the carcinogenic potential of ITCs. We also discuss the advantages and limitations of each ITC in BC treatment, furthering the consideration of ITCs in treatment strategies and for improving the prognosis of patients with BC.

scholarly journals Present Status, Limitations and Future Directions of Treatment Strategies Using Fucoidan-Based Therapies in Bladder Cancer

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3776
Author(s):  
Yasuyoshi Miyata ◽  
Tomohiro Matsuo ◽  
Kojiro Ohba ◽  
Kensuke Mitsunari ◽  
Yuta Mukae ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Adverse Events ◽  
Molecular Mechanisms ◽  
Immune Therapy ◽  
Treatment Strategies ◽  
Chemotherapeutic Agents ◽  
Protective Effects ◽  
Future Directions ◽  
Anti Cancer

Bladder cancer (BC) is a common urological cancer, with poor prognosis for advanced/metastatic stages. Various intensive treatments, including radical cystectomy, chemotherapy, immune therapy, and radiotherapy are commonly used for these patients. However, these treatments often cause complications and adverse events. Therefore, researchers are exploring the efficacy of natural product-based treatment strategies in BC patients. Fucoidan, derived from marine brown algae, is recognized as a multi-functional and safe substrate, and has been reported to have anti-cancer effects in various types of malignancies. Additionally, in vivo and in vitro studies have reported the protective effects of fucoidan against cancer-related cachexia and chemotherapeutic agent-induced adverse events. In this review, we have introduced the anti-cancer effects of fucoidan extracts in BC and highlighted its molecular mechanisms. We have also shown the anti-cancer effects of fucoidan therapy with conventional chemotherapeutic agents and new treatment strategies using fucoidan-based nanoparticles in various malignancies. Moreover, apart from the improvement of anti-cancer effects by fucoidan, its protective effects against cancer-related disorders and cisplatin-induced toxicities have been introduced. However, the available information is insufficient to conclude the clinical usefulness of fucoidan-based treatments in BC patients. Therefore, we have indicated the aspects that need to be considered regarding fucoidan-based treatments and future directions for the treatment of BC.

scholarly journals Anti-Cancer and Medicinal Potentials of Moringa Isothiocyanate

Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7512
Author(s):  
Yu-Yao Wu ◽  
Yan-Ming Xu ◽  
Andy T. Y. Lau
Keyword(s):  
Molecular Mechanisms ◽  
Relevant Literature ◽  
Treatment Strategies ◽  
Body Parts ◽  
Cancer Proliferation ◽  
Cancer Migration ◽  
Comprehensive Information ◽  
Anti Cancer ◽  
Future Direction ◽  
Moringa Isothiocyanate

Moringa oleifera (M. oleifera), which belongs to the Moringaceae family, is a common herb, rich in plant compounds. It has a variety of bioactive compounds that can act as antioxidants, antibiotics, anti-inflammatory and anti-cancer agents, etc., which can be obtained in different body parts of M. oleifera. Isothiocyanates (ITCs) from M. oleifera are one class of these active substances that can inhibit cancer proliferation and promote cancer cell apoptosis through multiple signaling pathways, thus curbing cancer migration and metastasis, at the same time they have little adverse effect on normal cells. There are multiple variants of ITCs in M. oleifera, but the predominant phytochemical is 4-(α-L-rhamnosyloxy)benzyl isothiocyanate, also known as moringa isothiocyanate (MIC-1). Studies have shown that MIC-1 has the possibility to be used clinically for the treatment of diabetes, neurologic diseases, obesity, ulcerative colitis, and several cancer types. In this review, we focus on the molecular mechanisms underlying the anti-cancer and anti-chronic disease effects of MIC-1, current trends, and future direction of MIC-1 based treatment strategies. This review combines the relevant literature of the past 10 years, in order to provide more comprehensive information of MIC-1 and to fully exploit its potentiality in the clinical settings.

scholarly journals Anti-Cancer and Protective Effects of Royal Jelly for Therapy-Induced Toxicities in Malignancies

2018 ◽  
Vol 19 (10) ◽  
pp. 3270 ◽  
Author(s):  
Yasuyoshi Miyata ◽  
Hideki Sakai
Keyword(s):  
Molecular Mechanisms ◽  
Royal Jelly ◽  
Biological Activities ◽  
Treatment Strategies ◽  
Protective Effects ◽  
Beneficial Effects ◽  
Glandular Secretion ◽  
Anti Cancer ◽  
The Future ◽  
Queen Honeybee

Royal jelly (RJ) is a glandular secretion produced by worker honeybees and is a special food for the queen honeybee. It results in a significant prolongation of the lifespan of the queen honeybee compared with the worker honeybees through anti-inflammatory, anti-oxidant and anti-microbial activities. Consequently, RJ is used as cosmetic and dietary supplement throughout the world. In addition, in vitro studies and animal experiments have demonstrated that RJ inhibits cell proliferation and stimulates apoptosis in various types of malignant cells and affects the production of various chemokines, anti-oxidants and growth factors and the expression of cancer-related molecules in patients with malignancies, especially in patients treated with anti-cancer agents. Therefore, RJ is thought to exert anti-cancer effects on tumor growth and exhibit protective functions against drug-induced toxicities. RJ has also been demonstrated to be useful for suppression of adverse events, the maintenance of the quality of life during treatment and the improvement of prognosis in animal models and patients with malignancies. To understand the mechanisms of the beneficial effects of RJ, knowledge of the changes induced at the molecular level by RJ with respect to cell survival, inflammation, oxidative stress and other cancer-related factors is essential. In addition, the effects of combination therapies of RJ and other anti-cancer agents or natural compounds are important to determine the future direction of RJ-based treatment strategies. Therefore, in this review, we have covered the following five issues: (1) the anti-cancer effects of RJ and its main component, 10-hydroxy-2-decenoic acid; (2) the protective effects of RJ against anti-cancer agent-induced toxicities; (3) the molecular mechanisms of such beneficial effects of RJ; (4) the safety and toxicity of RJ; and (5) the future directions of RJ-based treatment strategies, with a discussion on the limitations of the study of the biological activities of RJ.

scholarly journals Immunotherapy in the Treatment of Urothelial Bladder Cancer: Insights From Single-Cell Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Jingyu Zang ◽  
Kaiyan Ye ◽  
Yang Fei ◽  
Ruiyun Zhang ◽  
Haige Chen ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Single Cell ◽  
Molecular Mechanisms ◽  
Single Cell Analysis ◽  
Treatment Guidelines ◽  
Checkpoint Inhibitors ◽  
Cell Analysis ◽  
Urothelial Bladder Cancer ◽  
Global Challenge ◽  
Urothelial Bladder

Urothelial bladder cancer (UBC) is a global challenge of public health with limited therapeutic options. Although the emergence of cancer immunotherapy, most notably immune checkpoint inhibitors, represents a major breakthrough in the past decade, many patients still suffer from unsatisfactory clinical outcome. A thorough understanding of the fundamental cellular and molecular mechanisms responsible for antitumor immunity may lead to optimized treatment guidelines and new immunotherapeutic strategies. With technological developments and protocol refinements, single-cell approaches have become powerful tools that provide unprecedented insights into the kaleidoscopic tumor microenvironment and intricate cell-cell communications. In this review, we summarize recent applications of single-cell analysis in characterizing the UBC multicellular ecosystem, and discuss how to leverage the high-resolution information for more effective immune-based therapies.

Vascular toxicity associated with anti-angiogenic drugs

2020 ◽  
Vol 134 (18) ◽  
pp. 2503-2520
Author(s):  
Karla B. Neves ◽  
Augusto C. Montezano ◽  
Ninian N. Lang ◽  
Rhian M. Touyz
Keyword(s):  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Adenosine Diphosphate ◽  
No Production ◽  
Vascular Effects ◽  
Vegf Inhibitors ◽  
Vascular Toxicity ◽  
Endothelin System ◽  
Anti Cancer

Abstract Over the past two decades, the treatment of cancer has been revolutionised by the highly successful introduction of novel molecular targeted therapies and immunotherapies, including small-molecule kinase inhibitors and monoclonal antibodies that target angiogenesis by inhibiting vascular endothelial growth factor (VEGF) signaling pathways. Despite their anti-angiogenic and anti-cancer benefits, the use of VEGF inhibitors (VEGFi) and other tyrosine kinase inhibitors (TKIs) has been hampered by potent vascular toxicities especially hypertension and thromboembolism. Molecular processes underlying VEGFi-induced vascular toxicities still remain unclear but inhibition of endothelial NO synthase (eNOS), reduced nitric oxide (NO) production, oxidative stress, activation of the endothelin system, and rarefaction have been implicated. However, the pathophysiological mechanisms still remain elusive and there is an urgent need to better understand exactly how anti-angiogenic drugs cause hypertension and other cardiovascular diseases (CVDs). This is especially important because VEGFi are increasingly being used in combination with other anti-cancer dugs, such as immunotherapies (immune checkpoint inhibitors (ICIs)), other TKIs, drugs that inhibit epigenetic processes (histone deacetylase (HDAC) inhibitor) and poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors, which may themselves induce cardiovascular injury. Here, we discuss vascular toxicities associated with TKIs, especially VEGFi, and provide an up-to-date overview on molecular mechanisms underlying VEGFi-induced vascular toxicity and cardiovascular sequelae. We also review the vascular effects of VEGFi when used in combination with other modern anti-cancer drugs.

The Potential of T Cell Immunoglobulin and Mucin-Domain containing-3 (Tim-3) in Designing Novel Immunotherapy for Bladder Cancer

2021 ◽  
Vol 21 ◽  
Author(s):  
Monireh Mohsenzadegan ◽  
Parizad Bavandpour ◽  
Mohammad Reza Nowroozi ◽  
Erfan Amini ◽  
Masoumeh Kourosh-Arami ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
T Cells ◽  
T Cell ◽  
Tumor Immunity ◽  
Checkpoint Inhibitors ◽  
Number Of Patients ◽  
Anti Cancer ◽  
Domain 3

: Targeting inhibitory receptors on T cells in the tumor sites can promote effective anti-tumor immunity in bladder cancer. Unfortunately, the main dilemma is that a large number of patients remain refractory to CTLA-4, PD-1, and PD-L1 blockade therapies. T-cell immunoglobulin and mucin domain 3 (Tim-3) is an inhibitory receptor expressed on T cells and innate immune cells. Both in vivo and in vitro data from patients with advanced cancers support the role of Tim-3 inhibition in satisfactory anti-tumor immunity. In bladder cancer, the expression level of Tim-3 significantly increases with advanced pathological grade and T stage. Therefore, rationality implies that designing novel monoclonal antibodies reactive with Tim-3 alone or in combination with other checkpoint inhibitors may indicate a favorable response in bladder cancer. Here, we aimed to investigate the possibility of targeting Tim-3 as a novel anti-cancer treatment for bladder cancer.

scholarly journals Anti-Hepatocellular Carcinoma Biomolecules: Molecular Targets Insights

2021 ◽  
Vol 22 (19) ◽  
pp. 10774
Author(s):  
Nouf Juaid ◽  
Amr Amin ◽  
Ali Abdalla ◽  
Kevin Reese ◽  
Zaenah Alamri ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Molecular Targets ◽  
Quantitative Structure Activity Relationship ◽  
Efficient Treatment ◽  
Signaling Mechanisms ◽  
Anti Cancer ◽  
Therapeutic Molecules ◽  
Essential Resource

This report explores the available curative molecules directed against hepatocellular carcinoma (HCC). Limited efficiency as well as other drawbacks of existing molecules led to the search for promising potential alternatives. Understanding of the cell signaling mechanisms propelling carcinogenesis and driven by cell proliferation, invasion, and angiogenesis can offer valuable information for the investigation of efficient treatment strategies. The complexity of the mechanisms behind carcinogenesis inspires researchers to explore the ability of various biomolecules to target specific pathways. Natural components occurring mainly in food and medicinal plants, are considered an essential resource for discovering new and promising therapeutic molecules. Novel biomolecules normally have an advantage in terms of biosafety. They are also widely diverse and often possess potent antioxidant, anti-inflammatory, and anti-cancer properties. Based on quantitative structure–activity relationship studies, biomolecules can be used as templates for chemical modifications that improve efficiency, safety, and bioavailability. In this review, we focus on anti-HCC biomolecules that have their molecular targets partially or completely characterized as well as having anti-cancer molecular mechanisms that are fairly described.

Relationships between anticancer effects and serum gemcitabine levels, human antigen-R expression, and their combination in advanced urothelial cancer treated with gemcitabine and platinum agents.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 445-445
Author(s):  
Yuji Sagara ◽  
Yasuyoshi Miyata ◽  
Tsutomu Yuno ◽  
Kyohei Araki ◽  
Yuichiro Nakamura ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Treatment Strategies ◽  
Upper Urinary Tract ◽  
University Hospital ◽  
Active Metabolites ◽  
Serum Samples ◽  
Human Antigen R ◽  
Number Of Patients ◽  
Anti Cancer ◽  
Platinum Agents

445 Background: Combination therapy of gemcitabine (GEM) and platinum agents and immune-checkpoint inhibitors are standard regimens for advanced urothelial carcinoma (UC), and optimum selection is important to improve the prognosis. Human antigen R (HuR) increases the protein expression of the enzyme deoxycytidine kinase, which is involved in metabolizing the prodrug GEM into its active metabolites. HuR expression is a predictor for the response to gemcitabine-based chemotherapy in a variety of cancers. This study evaluated the relationship between combination pattern of serum GEM level and HuR expression in cancer cells and anti-cancer effects of GEM-based regimens in patients advanced UC. Methods: Twenty-seven advanced UC patients (bladder = 8 and upper urinary tract = 19) were treated with a combination of GEM and platinum agents (cisplatin = 15 and carboplatin = 12) as first-line chemotherapy in Nagasaki University Hospital. Serum samples were collected 30 min after GEM injection. HuR expression was examined by immunohistochemical methods. Results: Positive expression of HuR was detected in 17 (63.0%) patients, and the mean/SD of serum GEM level was 14.9/5.1 μg/mL. C-HuR expression was not associated with anti-cancer effect (P = 0.066). Serum GEM level in the progressive disease (PD) group (10.4/4.7 μg/mL) was lower than that in groups with CR + PR (16.2/3.7) or SD (16.3/6.1); however, these differences were not significant. For the anti-cancer effect of the combination of serum GEM level and HuR expression, all 3 patients with low GEM levels (under median) and negative HuR expression showed PD. In contrast, among 7 patients with high GEM levels and positive C-HuR expression, no patients showed PD, and relationship between their combination pattern and anti-cancer effect was significant (P = 0.010). Conclusions: Serum GEM level or HuR expression was not associated with anti-cancer effects; however, their combination pattern was significantly associated. Although we examined a small number of patients, our results are useful for determining treatment strategies in patients with advanced UC.

scholarly journals Bladder-Sparing Chemoradiotherapy Combined with Immune Checkpoint Inhibition for Locally Advanced Urothelial Bladder Cancer—A Review

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 38
Author(s):  
Jons W. van Hattum ◽  
Ben-Max de Ruiter ◽  
Jorg R. Oddens ◽  
Maarten C. C. M. Hulshof ◽  
Theo M. de Reijke ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Survival Data ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Locally Advanced ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Term Survival ◽  
First Choice ◽  
Bladder Sparing

Despite current treatment strategies, the 5-year overall survival of muscle-invasive bladder cancer (MIBC) is approximately 50%. Historically, radical cystectomy (RC) with neoadjuvant chemotherapy has been the first-choice treatment for this patient group. Recently, several studies have reported encouraging results of using immune checkpoint inhibitors (ICI) prior to RC. However, in recent years, bladder-sparing alternatives such as CRT have gained popularity. The effect of radiotherapy on the tumor microenvironment is an important rationale for combining CRT with ICI therapy. Worldwide, twelve immunochemoradiotherapy (iCRT) trials are ongoing. Each study employs a different chemotherapy and radiotherapy regimen and varies the timing of ICI administration concurrent to radiotherapy, adjuvant, or both. Five studies have presented (preliminary) results showing promising safety and short-term survival data. The first peer-reviewed publications are expected in the near future. The preclinical evidence and preliminary patient data demonstrate the potential of iCRT bladder-sparing treatment for bladder cancer.

scholarly journals Management of Urothelial Bladder Cancer in Clinical Practice: Real-World Answers to Difficult Questions

2019 ◽  
Vol 15 (8) ◽  
pp. 421-428 ◽  
Author(s):  
Nataliya Mar ◽  
Farshid Dayyani
Keyword(s):  
Bladder Cancer ◽  
Clinical Practice ◽  
Molecular Mechanisms ◽  
Checkpoint Inhibitors ◽  
Response To Treatment ◽  
Urothelial Bladder Cancer ◽  
Platinum Based Chemotherapy ◽  
Urothelial Bladder ◽  
Muscle Invasive ◽  
Gray Areas

Management of urothelial bladder cancer has historically been challenging as a result of a limited grasp of disease biology and few available systemic therapy options, mainly consisting of platinum-based chemotherapy. Improved understanding of molecular mechanisms underlying pathogenesis of muscle-invasive bladder cancer as well as their correlation with tumor behavior and response to treatment has emerged over the past few years. Remarkable therapeutic advances have been made with the introduction of checkpoint inhibitors, which have changed the course of this disease. Multiple agents with novel mechanisms of action are also actively being explored in ongoing clinical trials. These advances are exciting but may prove challenging in terms of how to apply this constantly evolving plethora of data to actual patients. This review addresses the gray areas and challenging questions that frequently arise in clinical practice.

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