Terminalia ivorensis demonstrates antioxidant properties and alters proliferation, genomic instability and migration of human colon cancer cells in vitro.

Colorectal cancer is a global killer that causes approximately 940 thousand deaths annually. Terminalia ivorensis (TI) is a tropical tree, the bark of which is used in African traditional medicine for the treatment of diabetes, malaria and ulcer. This study investigated TI as a potential anticancer agent in human colon cells in vitro.

Predicting Regression of Barrett's Esophagus-Can All the King's Men Put It Together Again?

The primary pre-neoplastic lesion of the lower esophagus in the vicinity of the gastroesophageal junction (GEJ) is any Barrett's esophageal lesions (BE), and esophageal neoplasia has increased in the US population with predispositions (Caucasian males, truncal obesity, age, and GERD). The responses to BE are endoscopic and screening cytologic programs with endoscopic ablation of various forms. The former have not been proven to be cost-effective and there are mixed results for eradication.

The Low-density Lipoprotein Receptor-related Protein 6 Pathway in the Treatment of Intestinal Barrier Dysfunction Induced by Hypoxia and Intestinal Microbiota through the Wnt/β-catenin Pathway.

Our study is to explore the key molecular of Low-density lipoprotein receptor-related protein 6 (LRP6) and the related Wnt/β-catenin pathway regulated by LRP6 during the intestinal barrier dysfunction. Colorectal protein profile analysis showed that LRP6 expression was decreased in dextran sulfate sodium (DSS)-induced colitis mice, and mice received fecal bacteria transplantation from stroke patients. Mice with intestinal hypoxia and intestinal epithelial cells cultured in hypoxia showed decreased expression of LRP6.

Suppression of Colon Tumorigenesis in Mutant Mice by a Novel PDE10 Inhibitor that Reduces Oncogenic β-Catenin.

Previous studies have reported that phosphodiesterase 10A (PDE10) is overexpressed in colon epithelium during early stages of colon tumorigenesis and essential for colon cancer cell growth. Here we describe a novel non-COX inhibitory derivative of the anti-inflammatory drug, sulindac, with selective PDE10 inhibitory activity, ADT 061. ADT 061 potently inhibited the growth of colon cancer cells expressing high levels of PDE10, but not normal colonocytes that do not express PDE10.

Leucovorin Rescue After Methotrexate Graft-Versus-Host Disease Prophylaxis Shortens the Duration of Mucositis, Time to Neutrophil Engraftment, and Hospital Length of Stay.

Oropharyngeal mucositis (OPM) is common following conditioning for allogeneic hematopoietic cell transplantation (alloHCT) and results in pain, functional status decline, need for nutritional support, infections, and prolonged length of stay (LOS). Methotrexate (MTX) graft-versus-host disease (GVHD) prophylaxis exacerbates OPM and slows hematopoietic engraftment, which may prolong LOS. Previous studies have demonstrated reduced OPM and more rapid engraftment when leucovorin (LCV) is added following MTX GVHD prophylaxis, yet this practice is controversial.

Proteomic Characterization of Colorectal Cancer Cells versus Normal-Derived Colon Mucosa Cells: Approaching Identification of Novel Diagnostic Protein Biomarkers in Colorectal Cancer.

In the western world, colorectal cancer (CRC) is the third most common cause of cancer-related deaths. Survival is closely related to the stage of cancer at diagnosis striking the clinical need for biomarkers capable of early detection. To search for possible biological parameters for early diagnosis of CRC we evaluated protein expression for three CREC (acronym: ab45, eticulocalbin, RC-55, alumenin) proteins: reticulocalbin, calumenin, and ERC-55 in a cellular model consisting of a normal derived colon mucosa cell line, NCM460, and a primary adenocarcinoma cell line of the colon, SW480.

Folate, genomic stability and colon cancer: The use of single cell gel electrophoresis in assessing the impact of folate in vitro, in vivo and in human biomonitoring.

Intake of folate (vitamin B) is strongly inversely linked with human cancer risk, particularly colon cancer. In general, people with the highest dietary intake of folate or with high blood folate levels are at a reduced risk (approx. 25%) of developing colon cancer.

MicroRNA-21 increases the expression level of occludin through regulating ROCK1 in prevention of intestinal barrier dysfunction.

Objective: The aim of this study is to investigate the role of molecular mechanism of microRNA (miR)-21 on tight junction (TJ)-proteins and its protective effects on the intestinal barrier.

Methods: TJ proteins and target genes expression were analyzed in miR-21 inhibition and overexpression NCM460 cell lines. To further verify the role of miR-21, the mmu-miR-21 intestinal epithelial conditional knockout (IKO) mice model was established.

Protective Effects of Let-7b on the Expression of Occludin by Targeting P38 MAPK in Preventing Intestinal Barrier Dysfunction.

Background/aims: Let-7b was dramatically reduced after a dicer knockout of mice with intestinal barrier function injuries. This paper aims to investigate the molecular mechanism of let-7b by targeting p38 MAPK in preventing intestinal barrier dysfunction.

Methods: A total of 186 patients were enrolled, with 93 in the control group and 93 in the PRO group.

Beta-catenin cleavage enhances transcriptional activation.

Nuclear activation of Wnt/β-catenin signaling is required for cell proliferation in inflammation and cancer. Studies from our group indicate that β-catenin activation in colitis and colorectal cancer (CRC) correlates with increased nuclear levels of β-catenin phosphorylated at serine 552 (pβ-Cat). Biochemical analysis of nuclear extracts from cancer biopsies revealed the existence of low molecular weight (LMW) pβ-Cat, increased to the exclusion of full size (FS) forms of β-catenin.

Upregulation of Cystathionine-β-Synthase in Colonic Epithelia Reprograms Metabolism and Promotes Carcinogenesis.

The trans-sulfuration enzyme cystathionine-β-synthase (CBS) and its product hydrogen sulfide (H2S) are aberrantly upregulated in colorectal cancers, where they contribute to tumor growth and progression by both autocrine and paracrine mechanisms. However, it is unknown whether the CBS/H2S axis plays a role in colorectal carcinogenesis. Here, we report upregulation of CBS in human biopsies of precancerous adenomatous polyps and show that forced upregulation of CBS in an adenoma-like colonic epithelial cell line is sufficient to induce metabolic and gene expression profiles characteristic of colorectal cancer cells.

Mitochondria sustain store-operated currents in colon cancer cells but not in normal colonic cells: reversal by non-steroidal anti-inflammatory drugs.

Tumor cells undergo a critical remodeling of intracellular Ca homeostasis that contribute to important cancer hallmarks. Store-operated Ca entry (SOCE), a Ca entry pathway modulated by mitochondria, is dramatically enhanced in colon cancer cells. In addition, most cancer cells display the Warburg effect, a metabolic switch from mitochondrial metabolism to glycolysis that provides survival advantages.

Epithelial TNF Receptor Signaling Promotes Mucosal Repair in Inflammatory Bowel Disease.

TNF plays an integral role in inflammatory bowel disease (IBD), as evidenced by the dramatic therapeutic responses in Crohn's disease (CD) patients induced by chimeric anti-TNF mAbs. However, treatment of CD patients with etanercept, a decoy receptor that binds soluble TNF, fails to improve disease. To explore this discrepancy, we investigated the role of TNF signaling in Wnt/β-catenin-mediated intestinal stem cell and progenitor cell expansion in CD patients, human cells, and preclinical mouse models.

Palliative Care Office Hours for Patients with Hematologic Malignancies: An Innovative Model for Symptom Management and Education.

Background: Palliative care programs are experiencing rapid growth, with demand for consults surpassing staffing. Innovative models are needed to equip nonpalliative care providers to manage basic palliative care issues.

Objectives: To develop a novel program of palliative care office hours for hematologic oncology advanced practice providers, and to evaluate its impact on palliative care consult volume and composition.

Transcriptomic Analysis of Calcium Remodeling in Colorectal Cancer.

Colorectal cancer (CRC) cells undergo the remodeling of intracellular Ca homeostasis, which contributes to cancer hallmarks such as enhanced proliferation, invasion and survival. Ca remodeling includes critical changes in store-operated Ca entry (SOCE) and Ca store content. Some changes have been investigated at the molecular level.

Butyrate alters expression of cytochrome P450 1A1 and metabolism of benzo[a]pyrene via its histone deacetylase activity in colon epithelial cell models.

Butyrate, a short-chain fatty acid produced by fermentation of dietary fiber, is an important regulator of colonic epithelium homeostasis. In this study, we investigated the impact of this histone deacetylase (HDAC) inhibitor on expression/activity of cytochrome P450 family 1 (CYP1) and on metabolism of carcinogenic polycyclic aromatic hydrocarbon, benzo[a]pyrene (BaP), in colon epithelial cells. Sodium butyrate (NaBt) strongly potentiated the BaP-induced expression of CYP1A1 in human colon carcinoma HCT116 cells.

Scripted Nurse Visits: A Resource-Efficient Palliative Care Model for Ventricular Assist Devices.

Background: The Center for Medicare Services (CMS) requires palliative care involvement for patients who receive a destination therapy ventricular assist device (VAD). Creative solutions are needed to meet this requirement in the context of limited palliative care resources.

Purpose: To evaluate a novel program in which a nurse conducts scripted pre-VAD visits to promote advance care planning and to triage the need for a full palliative care consult.

N52 monodeamidated Bcl‑xL shows impaired oncogenic properties in vivo and in vitro.

Bcl-xL is a member of the Bcl-2 family, playing a critical role in the survival of tumor cells. Here, we show that Bcl-xL oncogenic function can be uncoupled from its anti-apoptotic activity when it is regulated by the post-translational deamidation of its Asn52.Bcl-xL activity can be regulated by post-translational modifications: deamidation of Asn52 and 66 into Asp residues was reported to occur exclusively in response to DNA damage, and to cripple its anti-apoptotic activity.

Gastrointestinal digested Sambucus nigra L. fruit extract protects in vitro cultured human colon cells against oxidative stress.

Elderberry (EDB) Sambucus nigra L. is one of the oldest medicinal plants which is useful for therapeutic and nutritional purposes due to a large amount of biologically active constituents, including compounds with a high antioxidant capacity. The present study focused on the antioxidant potential of the colon-available EDB fruit extract, derived from the artificial gastrointestinal tract, with regard to human colonic mucosa cells cultured in vitro.

A Cytosolic Multiprotein Complex Containing p85α Is Required for β-Catenin Activation in Colitis and Colitis-associated Cancer.

Wnt/β-catenin signaling is required for crypt structure maintenance. We previously observed nuclear accumulation of Ser-552 phosphorylated β-catenin (pβ-Cat(Ser-552)) in intestinal epithelial cells (IEC) during colitis and colitis-associated cancer. Data here delineate a novel multiprotein cytosolic complex (MCC) involved in β-catenin signaling in the intestine.

Loss of PTEN Facilitates Rosiglitazone-Mediated Enhancement of Platinum(IV) Complex LA-12-Induced Apoptosis in Colon Cancer Cells.

We demonstrated for the first time an outstanding ability of rosiglitazone to mediate a profound enhancement of LA-12-induced apoptosis associated with activation of mitochondrial pathway in human colon cancer cells. This effect was preferentially observed in the G1 cell cycle phase, independent on p53 and PPARγ proteins, and accompanied with significant changes of selected Bcl-2 family protein levels. Further stimulation of cooperative synergic cytotoxic action of rosiglitazone and LA-12 was demonstrated in the cells deficient for PTEN, where mitochondrial apoptotic pathway was more stimulated and G1-phase-associated dying was reinforced.

Colorectal cancer-related mutant KRAS alleles function as positive regulators of autophagy.

The recent interest to modulate autophagy in cancer therapy has been hampered by the dual roles of this conserved catabolic process in cancer, highlighting the need for tailored approaches. Since RAS isoforms have been implicated in autophagy regulation and mutation of the KRAS oncogene is highly frequent in colorectal cancer (CRC), we questioned whether/how mutant KRAS alleles regulate autophagy in CRC and its implications. We established two original models, KRAS-humanized yeast and KRAS-non-cancer colon cells and showed that expression of mutated KRAS up-regulates starvation-induced autophagy in both.