Therapeutic Potential of Emodin for Gastrointestinal Cancers

Gastrointestinal (GI) cancers cause one-third of all cancer-related deaths worldwide. Natural compounds are emerging as alternative or adjuvant cancer therapies given their distinct advantage of manipulating multiple pathways to both suppress tumor growth and alleviate cancer comorbidities; however, concerns regarding efficacy, bioavailability, and safety are barriers to their development for clinical use. Emodin (1,3,8-trihydroxy-6-methylanthraquinone), a Chinese herb-derived anthraquinone, has been shown to exert anti-tumor effects in colon, liver, and pancreatic cancers. While the mechanisms underlying emodin’s tumoricidal effects continue to be unearthed, recent evidence highlights a role for mitochondrial mediated apoptosis, modulated stress and inflammatory signaling pathways, and blunted angiogenesis. The goals of this review are to (1) highlight emodin’s anti-cancer properties within GI cancers, (2) discuss the known anti-cancer mechanisms of action of emodin, (3) address emodin’s potential as a treatment complementary to standard chemotherapeutics, (4) assess the efficacy and bioavailability of emodin derivatives as they relate to cancer, and (5) evaluate the safety of emodin.

All You Need to Know About UGT1A1 Genetic Testing for Patients Treated With Irinotecan: A Practitioner-Friendly Guide

Irinotecan is an anticancer agent widely used for the treatment of solid tumors, including colorectal and pancreatic cancers. Severe neutropenia and diarrhea are common dose-limiting toxicities of irinotecan-based therapy, and UGT1A1 polymorphisms are one of the major risk factors of these toxicities. In 2005, the US Food and Drug Administration revised the drug label to indicate that patients with UGT1A1*28 homozygous genotype should receive a decreased dose of irinotecan. However, UGT1A1*28 testing is not routinely used in the clinic, and specific reasons include lack of access to concise information on this wide issue as well as mixed recommendations by regulatory and professional entities. To assist oncologists in assessing whether and when to use UGT1A1 genetic testing in patients receiving irinotecan-based therapies, this article provided (1) essential knowledge of UGT1A1 polymorphisms; (2) an update on the impact of UGT1A1 polymorphisms on efficacy and toxicity of contemporary irinotecan-based regimens; (3) dosing adjustments based upon the UGT1A1 genotypes, and (4) recommendations from currently available guidelines from the US and international scientific consortia and major oncology societies.

CRISPR and KRAS: a match yet to be made

CRISPR (clustered regularly interspaced short palindromic repeats) systems are one of the most fascinating tools of the current era in molecular biotechnology. With the ease that they provide in genome editing, CRISPR systems generate broad opportunities for targeting mutations. Specifically in recent years, disease-causing mutations targeted by the CRISPR systems have been of main research interest; particularly for those diseases where there is no current cure, including cancer. KRAS mutations remain untargetable in cancer. Mutations in this oncogene are main drivers in common cancers, including lung, colorectal and pancreatic cancers, which are severe causes of public health burden and mortality worldwide, with no cure at hand. CRISPR systems provide an opportunity for targeting cancer causing mutations. In this review, we highlight the work published on CRISPR applications targeting KRAS mutations directly, as well as CRISPR applications targeting mutations in KRAS-related molecules. In specific, we focus on lung, colorectal and pancreatic cancers. To date, the limited literature on CRISPR applications targeting KRAS, reflect promising results. Namely, direct targeting of mutant KRAS variants using various CRISPR systems resulted in significant decrease in cell viability and proliferation in vitro, as well as tumor growth inhibition in vivo. In addition, the effect of mutant KRAS knockdown, via CRISPR, has been observed to exert regulatory effects on the downstream molecules including PI3K, ERK, Akt, Stat3, and c-myc. Molecules in the KRAS pathway have been subjected to CRISPR applications more often than KRAS itself. The aim of using CRISPR systems in these studies was mainly to analyze the therapeutic potential of possible downstream and upstream effectors of KRAS, as well as to discover further potential molecules. Although there have been molecules identified to have such potential in treatment of KRAS-driven cancers, a substantial amount of effort is still needed to establish treatment strategies based on these discoveries. We conclude that, at this point in time, despite being such a powerful directed genome editing tool, CRISPR remains to be underutilized for targeting KRAS mutations in cancer. Efforts channelled in this direction, might pave the way in solving the long-standing challenge of targeting the KRAS mutations in cancers.

Garlic (Allium sativum L.): Its Chemistry, Nutritional Composition, Toxicity and Anticancer Properties

: The current review discuss the chemistry, nutritional composition, toxicity, and biological functions of garlic and its bioactive compounds against various types of cancers via different anticancer mechanisms. Several scientific documents were found in reliable literature and searched in databases viz Science Direct, PubMed, Web of Science, Scopus and Research Gate were carried out using keywords such as “garlic”, “garlic bioactive compounds”, “anticancer mechanisms of garlic”, “nutritional composition of garlic”, and others. Garlic contains several phytoconstituents with activities against cancer, and these compounds such as diallyl trisulfide (DATS), allicin, and diallyl disulfide (DADS), diallyl sulfide (DAS), and allyl mercaptan (AM). The influence of numerous garlic-derived products, phytochemicals, and nanoformulations on the liver, oral, prostate, breast, gastric, colorectal, skin, and pancreatic cancers has been studied. Based on our search, the bioactive molecules in garlic were found to inhibit the various phases of cancer. Moreover, the compounds in this plant also abrogate the peroxidation of lipids, activity of nitric oxide synthase, epidermal growth factor (EGF) receptor, nuclear factor-kappa B (NF-κB), protein kinase C, and regulate cell cycle and survival signaling cascades. Hence, garlic and its bioactive molecules exhibit the aforementioned mechanistic actions and thus, they could be used to inhibit the induction, development and progression of cancer. The review describes the nutritional Composition of garlic, its bioactive molecules, and nanoformulations against various types of cancers, as well as the potential for developing these agents as antitumor drugs.

Outcome and early complications of Endoscopic Retrograde Cholangio-Pancreatography (ERCP): a cross-sectional study on 626 Patients

Background. ERCP is the gold standard procedure for diagnosis and potential treatment of biliary-pancreatic disorders with various distributions in different areas of the world. The study aimed to evaluate the findings, outcome, complications and technical experiences of ERCP, also by considering the correlation of findings with liver function tests (LFT) and imaging. Methods. In this descriptive – cross sectional data-based study for 12 years from 2007, 626 (43.9% male and 56.1%female; mean age 60 Ys) consecutive patients were subjected with therapeutic purpose at two referral hospitals. Results. Epigastric pain (40%), jaundice (39.4%) and pruritus (38.1%) were the most common indications. CBD was cannulated by optimal wire- guided sphincterotomy in 486(77.6%) patients. Precut was performed in 65(10.6%) with successful cannulation in 61 cases (93.8%) and 7.7% of complications, including perforation. A total success rate of 98% was obtained. The most common diagnoses were CBD stone(s) in 322 (51.4%) and biliary-pancreatic cancers in 114 (18.2%) of cases. No LFT (ALT, ALP and Bilirubin) predicted the diagnoses. The higher concordance rate of imaging studies in comparison with ERCP was 75% for stone(s) and the lower rate of 11.1% for tumors. Metallic stents were used in 15(2.4%) of inoperable malignant cases with life expectancy of more than 6 months. Complications occurred in 29 cases (4.6%) including duodenal perforation (0.8%), pancreatitis (1.6%) and bleeding (1.2%). Mortality rate was 0.4%. Conclusion. Although no single laboratory or imaging can exactly predict the finding or outcome, but by considering judicious case selection, appropriate use of available tools and standard techniques, the procedure could be safe with a few complications and higher success rates.

Effect of metformin on 18F-fluorodeoxyglucose uptake and positron emission tomographic imaging

Metformin is widely used to treat diabetes, but induces changes in glucose uptake in both normal organs and tumors. Here, we review the effects of metformin on the uptake of 18F-fluorodeoxyglucose (18F-FDG) in tissues and tumors, and its influence on 18F-FDG positron emission tomographic imaging (18F-FDG PET), as well as the mechanisms involved. This is an important issue, because metformin has diverse effects on tissue uptake of 18F-FDG, and this can affect the quality and interpretation of PET images. Metformin increases glucose uptake in the gastrointestinal tract, cerebral white matter, and the kidney, while regions of the cerebrum associated with memory show decreased glucose uptake, and the myocardium shows no change. Hepatocellular carcinoma and breast cancer show increased glucose uptake after metformin administration, while thyroid cancer shows decreased uptake, and colon and pancreatic cancers show no change. A high-energy diet increases 18F-FDG uptake, but this effect is blocked by metformin. Withdrawal of metformin 48 h before PET image acquisition is widely recommended. However, based on our review of the literature, we propose that the differentiation of metformin discontinuation could be reasonable. But future clinical trials are still needed to support our viewpoint.

The Neurotensinergic System: A Target for Cancer Treatment

Background: The scientific interest regarding the involvement of peptides in cancer has increased in the last years. In tumor cells the overexpression of peptides and their receptors is known and new therapeutic targets for the treatment of cancer have been suggested. The overexpression of the neurotensinergic system has been associated with poor prognosis, tumor size, higher tumor aggressiveness, increased relapse risk and worse sensitivity to chemotherapy agents. Objective: The aim of this review is to update the findings regarding the involvement of the neurotensinergic system in cancer to suggest anticancer therapeutic strategies targeting this system. The neurotensin (NT) precursor, NT and its receptors (NTR) and the involvement of the neurotensinergic system in lung, breast, prostate, gastric, colon, liver and pancreatic cancers, glioblastoma, neuroendocrine tumors and B-cell leukemia will be mentioned and discussed as well as the signaling pathways mediated by NT. Some research lines to be developed in the future will be suggested such as: molecules regulating the expression of the NT precursor, influence of the diet in the development of tumors, molecules and signaling pathways activated by NT and antitumor therapeutic strategies targeting the neurotensinergic system. Conclusion: NT, via the NTR, exerts oncogenic (tumor cell proliferation, invasion, migration, angiogenesis) and antiapoptotic effects, whereas NTR antagonists inhibit these effects. NTR expression can be used as a diagnostic tool/therapeutic target and the administration of NTR antagonists as antitumor drugs could be a therapeutic strategy to treat tumors overexpressing NTR.