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World Journal of Gastroenterology Nov 2020Prediction of survival after the treatment of hepatocellular carcinoma (HCC) has been widely investigated, yet remains inadequate. The application of artificial... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Prediction of survival after the treatment of hepatocellular carcinoma (HCC) has been widely investigated, yet remains inadequate. The application of artificial intelligence (AI) is emerging as a valid adjunct to traditional statistics due to the ability to process vast amounts of data and find hidden interconnections between variables. AI and deep learning are increasingly employed in several topics of liver cancer research, including diagnosis, pathology, and prognosis.
AIM
To assess the role of AI in the prediction of survival following HCC treatment.
METHODS
A web-based literature search was performed according to the Preferred Reporting Items for Systemic Reviews and Meta-Analysis guidelines using the keywords "artificial intelligence", "deep learning" and "hepatocellular carcinoma" (and synonyms). The specific research question was formulated following the patient (patients with HCC), intervention (evaluation of HCC treatment using AI), comparison (evaluation without using AI), and outcome (patient death and/or tumor recurrence) structure. English language articles were retrieved, screened, and reviewed by the authors. The quality of the papers was assessed using the Risk of Bias In Non-randomized Studies of Interventions tool. Data were extracted and collected in a database.
RESULTS
Among the 598 articles screened, nine papers met the inclusion criteria, six of which had low-risk rates of bias. Eight articles were published in the last decade; all came from eastern countries. Patient sample size was extremely heterogenous ( = 11-22926). AI methodologies employed included artificial neural networks (ANN) in six studies, as well as support vector machine, artificial plant optimization, and peritumoral radiomics in the remaining three studies. All the studies testing the role of ANN compared the performance of ANN with traditional statistics. Training cohorts were used to train the neural networks that were then applied to validation cohorts. In all cases, the AI models demonstrated superior predictive performance compared with traditional statistics with significantly improved areas under the curve.
CONCLUSION
AI applied to survival prediction after HCC treatment provided enhanced accuracy compared with conventional linear systems of analysis. Improved transferability and reproducibility will facilitate the widespread use of AI methodologies.
Topics: Artificial Intelligence; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Neoplasm Recurrence, Local; Prognosis; Reproducibility of Results
PubMed: 33268955
DOI: 10.3748/wjg.v26.i42.6679 -
International Journal of Molecular... Aug 2020Melanoma is the fourth most common type of cancer diagnosed in Australians after breast, prostate, and colorectal cancers. While there has been substantial progress in...
Melanoma is the fourth most common type of cancer diagnosed in Australians after breast, prostate, and colorectal cancers. While there has been substantial progress in the treatment of cancer in general, malignant melanoma, in particular, is resistant to existing medical therapies requiring an urgent need to develop effective treatments with lesser side effects. Several studies have shown that "cannabinoids", the major compounds of the plant, can reduce cell proliferation and induce apoptosis in melanoma cells. Despite prohibited use of in most parts of the world, in recent years there have been renewed interests in exploiting the beneficial health effects of the plant-derived compounds. Therefore, the aim of this study was in the first instance to review the evidence from in vivo studies on the effects of cannabinoids on melanoma. Systematic searches were carried out in PubMed, Embase, Scopus, and ProQuest Central databases for relevant articles published from inception. From a total of 622 potential studies, six in vivo studies assessing the use of cannabinoids for treatment of melanoma were deemed eligible for the final analysis. The findings revealed cannabinoids, individually or combined, reduced tumor growth and promoted apoptosis and autophagy in melanoma cells. Further preclinical and animal studies are required to determine the underlying mechanisms of cannabinoids-mediated inhibition of cancer-signaling pathways. Well-structured, randomized clinical studies on cannabinoid use in melanoma patients would also be required prior to cannabinoids becoming a viable and recognized therapeutic option for melanoma treatment in patients.
Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Cannabinoids; Cell Proliferation; Clinical Trials as Topic; Disease Models, Animal; Humans; Melanocytes; Melanoma; Mice; Skin Neoplasms; Survival Analysis; Tumor Burden; Tumor Cells, Cultured; Melanoma, Cutaneous Malignant
PubMed: 32839414
DOI: 10.3390/ijms21176040 -
Drug Resistance Updates : Reviews and... May 2020Multidrug resistance (MDR) is the dominant cause of the failure of cancer chemotherapy. The design of antitumor drugs that are able to evade MDR is rapidly evolving,...
Multidrug resistance (MDR) is the dominant cause of the failure of cancer chemotherapy. The design of antitumor drugs that are able to evade MDR is rapidly evolving, showing that this area of biomedical research attracts great interest in the scientific community. The current review explores promising recent approaches that have been developed with the aim of circumventing or overcoming MDR. Encouraging results have been obtained in the investigation of the MDR-modulating properties of various classes of natural compounds and their analogues. Inhibition of P-gp or downregulation of its expression have proven to be the main mechanisms by which MDR can be surmounted. The use of hybrid molecules that are able to simultaneously interact with two or more cancer cell targets is currently being explored as a means to circumvent drug resistance. This strategy is based on the design of hybrid compounds that are obtained either by merging the structural features of separate drugs, or by conjugating two drugs or pharmacophores via cleavable/non-cleavable linkers. The approach is highly promising due to the pharmacokinetic and pharmacodynamic advantages that can be achieved over the independent administration of the two individual components. However, it should be stressed that the task of obtaining successful multivalent drugs is a very challenging one. The conjugation of anticancer agents with nitric oxide (NO) donors has recently been developed, creating a particular class of hybrid that can combat tumor drug resistance. Appropriate NO donors have been shown to reverse drug resistance via nitration of ABC transporters and by interfering with a number of metabolic enzymes and signaling pathways. In fact, hybrid compounds that are produced by covalently attaching NO-donors and antitumor drugs have been shown to elicit a synergistic cytotoxic effect in a variety of drug resistant cancer cell lines. Another strategy to circumvent MDR is based on nanocarrier-mediated transport and the controlled release of chemotherapeutic drugs and P-gp inhibitors. Their pharmacokinetics are governed by the nanoparticle or polymer carrier and make use of the enhanced permeation and retention (EPR) effect, which can increase selective delivery to cancer cells. These systems are usually internalized by cancer cells via endocytosis and accumulate in endosomes and lysosomes, thus preventing rapid efflux. Other modalities to combat MDR are described in this review, including the pharmaco-modulation of acridine, which is a well-known scaffold in the development of bioactive compounds, the use of natural compounds as means to reverse MDR, and the conjugation of anticancer drugs with carriers that target specific tumor-cell components. Finally, the outstanding potential of in silico structure-based methods as a means to evaluate the ability of antitumor drugs to interact with drug transporters is also highlighted in this review. Structure-based design methods, which utilize 3D structural data of proteins and their complexes with ligands, are the most effective of the in silico methods available, as they provide a prediction regarding the interaction between transport proteins and their substrates and inhibitors. The recently resolved X-ray structure of human P-gp can help predict the interaction sites of designed compounds, providing insight into their binding mode and directing possible rational modifications to prevent them from becoming P-gp drug substrates. In summary, although major efforts were invested in the search for new tools to combat drug resistant tumors, they all require further implementation and methodological development. Further investigation and progress in the abovementioned strategies will provide significant advances in the rational combat against cancer MDR.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP-Binding Cassette Transporters; Acridines; Antineoplastic Agents; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Drug Design; Drug Resistance, Neoplasm; Glycoconjugates; Humans; Nanoparticles; Neoplasms; Nitric Oxide; Plant Preparations; Polymers; Technology, Pharmaceutical
PubMed: 32087558
DOI: 10.1016/j.drup.2020.100682 -
Frontiers in Pharmacology 2019Glucomannan, long recognized as the active ingredient of the traditional Chinese medicinal herb Konjac glucomannan, is a naturally occurring polysaccharide existing in... (Review)
Review
Glucomannan, long recognized as the active ingredient of the traditional Chinese medicinal herb Konjac glucomannan, is a naturally occurring polysaccharide existing in certain plant species and fungi. Due to its special property to also serve as a dietary supplement, glucomannan has been widely applied in clinic to lower body weight and circulation cholesterol level and to treat constipation, diabetes, and arterial sclerosis. Besides the regulatory role engaged with gastroenterological and metabolic syndrome, recently, its therapeutic effect and the underlying mechanisms in treating cancerous diseases have been appreciated by mounting researches. The present review aims to emphasize the multifaceted aspects of how glucomannan exerts its anti-tumor function.
PubMed: 31507423
DOI: 10.3389/fphar.2019.00930 -
BMC Cancer Jun 2019Numerous studies have explored the anti-tumor effect of berberine (BBR), but little clinical evidence guides the use of BBR in cancer patients. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Numerous studies have explored the anti-tumor effect of berberine (BBR), but little clinical evidence guides the use of BBR in cancer patients.
OBJECTIVES
Our aim was to investigate the impact of BBR on various cancers in healthy animals to promote the transformation from bench to bed.
SEARCH METHODS
PubMed, Embase, Springer, and Cochrane databases were searched from January 2000 to October 2018 for relevant articles.
SELECTION CRITERIA
Only published studies focusing on the relationship between BBR and various cancers in vivo were qualified. Two review authors independently assessed the risk of bias for each study, and any disagreement was resolved by discussion or by involving a third assessor.
RESULTS
A total of 26 studies from 2000 to 2018, focusing on various cancer types, including breast cancer, liver cancer, colorectal cancer, nasopharyngeal carcinoma, lung cancer, gastric cancer, neuroepithelial cancer, endometrial carcinoma, esophageal cancer, tongue cancer, cholangiocarcinoma, and sarcoma were included. Overall, BBR reduced tumor volume (SMD =3.72, 95% CI: 2.89, 4.56, Z = 8.73, p < 0.00001) and tumor weight (SMD =2.35, 95% CI: 1.51, 3.19, Z = 5.50, p < 0.00001) in a linear The dose-response relationship (Pearson r = - 0.6717, p < 0.0001 in tumor volume analysis; Pearson r = - 0.7704, p < 0.0005 in tumor weight analysis). BBR inhibited angiogenesis in tumor tissues (SMD = 4.29, 95% CI: 2.14, 6.44, Z = 3.92, p < 0.00001), but it had no significant effect on the body weight of experimental animals (SMD = 0.11, 95% CI: - 0.70, 0.92, Z = 0.27, p = 0.78). Publication bias was not detected.
CONCLUSION
BBR exerted anti-tumor effects in a variety of tumors in vivo, especially breast cancer and lung cancer, and the evidence was still insufficient in colorectal cancer and gastric cancer.
Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Berberine; Berberis; Body Weight; Cricetinae; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Guinea Pigs; Haplorhini; Horses; Humans; Mice; Neoplasms; Phytotherapy; Plant Extracts; Rabbits; Rats; Sheep; Tumor Burden
PubMed: 31208348
DOI: 10.1186/s12885-019-5791-1 -
RSC Advances Jan 2019Colorectal cancer (CRC) is one of the most malignant cancers resulting from abnormal metabolism alterations. As one of the essential amino acids, tryptophan has a... (Review)
Review
Colorectal cancer (CRC) is one of the most malignant cancers resulting from abnormal metabolism alterations. As one of the essential amino acids, tryptophan has a variety of physiological functions, closely related to regulation of immune system, central nervous system, gastrointestinal nervous system and intestinal microflora. Colorectal cancer, a type of high-grade malignancy disease, stems from a variety of factors and often accompanies inflammatory reactions, dysbacteriosis, and metabolic disorders. Colorectal cancer accompanies inflammation and imbalance of intestinal microbiota and affects tryptophan metabolism. It is known that metabolites, rate-limiting enzymes, and ARH in tryptophan metabolism are associated with the development of CRC. Specifically, IDO1 may be a potential therapeutic target in colorectal cancer treatment. Furthermore, the reduction of tryptophan amount is proportional to the poor quality of life for colorectal cancer patients. This paper aims to discuss the role of tryptophan metabolism in a normal organism and investigate the relationship between this amino acid and colorectal cancer. This study is expected to provide theoretical support for research related to targeted therapy for colorectal cancer. Furthermore, strategies that modify tryptophan metabolism, effectively inhibiting tumor progression, may be more effective for CRC treatment.
PubMed: 35518968
DOI: 10.1039/c8ra08520j -
Nutrients Oct 2018Fermented wheat germ extract (FWGE; trade name AVEMAR) is a natural compound derived from industrial fermentation of wheat germ. Its potential anticancer properties has...
Fermented wheat germ extract (FWGE; trade name AVEMAR) is a natural compound derived from industrial fermentation of wheat germ. Its potential anticancer properties has emerged from recent studies. The aim of this systematic review is to summarize the data available in the scientific literature concerning the in vitro activity of FWGE on malignant cells. A systematic review of English articles in electronic databases has been performed. The primary outcomes of the review regarded types of cancer cell lines subjected to the investigation and the main results concerning cell viability, proliferation, and apoptosis observed within the studies. Sixteen articles were included in the final qualitative analysis. Various types of cancer cells treated with FWGE have been analyzed, showing mainly cytotoxic effects, alteration of the cell cycle, antiproliferative effects, and induction of apoptosis. FWGE can be a promising drug component in cancer treatment; however, further in vitro and in vivo studies are necessary to prove its effectiveness and safety in humans.
Topics: Cell Line, Tumor; Cell Proliferation; Cell Survival; Fermentation; Humans; Plant Extracts; Triticum
PubMed: 30347664
DOI: 10.3390/nu10101546 -
Integrative Cancer Therapies Dec 2018A continuous challenge in cancer management is to improve treatment efficacy and to diminish its side effects. Consequently, new conventional and unconventional drugs...
A continuous challenge in cancer management is to improve treatment efficacy and to diminish its side effects. Consequently, new conventional and unconventional drugs and bioactive compounds from plants are constantly developed, characterized, and used for in vitro and in vivo models. This review focuses on the antitumor properties of Calendula officinalis, its biological and molecular effects in tumor cells and animal models, as well as its role in cancer palliative care. A systematic review of studies describing the cytotoxic role of C officinalis and its therapeutic role on cancer cells were carried out using the PubMed database. Albeit C officinalis extracts have cytotoxic activity toward different cancer cell lines, a high grade of variation between studies was observed, depending on plant organ subjected to extraction, extraction method, and the cancer cell lines used for each study. Nevertheless, its cytotoxic activity is related to a few bioactive compounds, presenting multiple roles in both activation of proapoptotic proteins and decreasing the expression of the proteins that inhibit cell death. Moreover, due to its anti-genotoxic/protective as well as antitumor and antimetastatic effects proven in animal models, C officinalis could have important future implications in developing novel cancer treatment strategies, while until now it has been used especially for diminishing the side effects of radiotherapy.
Topics: Animals; Antineoplastic Agents; Apoptosis; Calendula; Humans; Neoplasms; Palliative Care; Phytotherapy; Plant Extracts
PubMed: 30289008
DOI: 10.1177/1534735418803766 -
PloS One 2018Cancer is an increasingly frequent malignancy worldwide, and despite the advances in drug development, it is still necessary to develop new plant-derived medicines....
Cancer is an increasingly frequent malignancy worldwide, and despite the advances in drug development, it is still necessary to develop new plant-derived medicines. Euterpe oleracea (açaí) is abundant in South and Central America and has health benefits due to its high levels of phytochemicals, including lignans and polyphenols. The aim of this review was to systematically describe the safety and antitumor effects of açaí in preclinical models using rodents to provide a more comprehensive assessment of açaí for both therapeutic uses and the development of future clinical studies in cancer. Eligible studies were identified using four international databases (PubMed, Medline, Lilacs and SciELO) from their inception date through December 2017. The included studies were analyzed with methodological rigor (QATRS) to enable better quality control for these experimental studies. Sixty publications were identified in the databases, but only 9 articles were eligible: 6 evaluated the pharmacological effects of açaí in animal models of cancer (1 model each of esophageal cancer, urothelial cancer, melanoma and Walker-256 tumor and 2 models of colon cancer), and 3 were toxicological assays using preclinical models with rodents. Overall, 747 animals were analyzed. On a QATRS score scale of 0-20, the quality of the studies ranged from 16 to 20 points. Pulp was the main fraction of açaí administered, and an oral administration route was most common. The açaí dosage administered by gavage ranged from 30 mg/kg to 40,000 mg/kg, and açaí fed in the diet accounted for 2.5% to 5% of the diet. The anticarcinogenic and chemopreventive activities of açaí were observed in all experimental models of cancer and reduced the incidence, tumor cell proliferation, multiplicity and size of the tumors due to the antiinflammatory, antiproliferative and proapoptotic properties of açaí. No genotoxic effects were observed after açaí administration. The results of this review suggest that açaí is safe and can be used as a chemoprotective agent against cancer development. Açaí therapy may be a novel strategy for treating cancer.
Topics: Animals; Antineoplastic Agents; Euterpe; Humans; Plant Extracts
PubMed: 29966007
DOI: 10.1371/journal.pone.0200101 -
Chemistry Central Journal May 2018Dioscorea nipponica Makino is a perennial twining herbs belonging to the family Dioscoreaceae, which is mainly distributed in the northeastern, northern, eastern and... (Review)
Review
Dioscorea nipponica Makino is a perennial twining herbs belonging to the family Dioscoreaceae, which is mainly distributed in the northeastern, northern, eastern and central regions of China. Traditionally, the rhizome of this herb has been commonly used by Miao and Meng ethnic groups of China to treat rheumatoid arthritis, pain in the legs and lumbar area, Kashin Beck disease, bruises, sprains, chronic bronchitis, cough and asthma. Modern pharmacological studies have discovered that this herb possesses anti-tumor, anti-inflammatory, anti-diuretic, analgesic, anti-tussive, panting-calming and phlegm-dispelling activities, along with enhancing immune function and improving cardiovascular health. In recent years, both fat-soluble and water-soluble steroidal saponins were isolated from the rhizomes of D. nipponica using silica gel column chromatography, thin layer chromatography and high performance liquid chromatography methods. Saponin and sapogenins are mainly responsible for most of the pharmacological effects of this plant. Further, the chemical components of the aboveground parts contain more than 10 kinds of phenanthrene derivatives. The present review summarizes the knowledge concerning the geographical distribution, chemical composition, pharmacological effects, toxicology studies and clinical applications of D. nipponica.
PubMed: 29748731
DOI: 10.1186/s13065-018-0423-4