Colon Treatment Resistance Stem like

An innate immune system intricately leverages unique mechanisms to inhibit colonization of external invasive Bacteria, for example human defensin-6, through responsive encapsulation of bacteria. Infection and accompanying antibiotic resistance stemming from Gram-negative bacteria aggregation represent an emerging public health crisis, which calls for research into novel anti-bacterial therapeutics. Herein, inspired by naturally found host-defense peptides, we design a defensin-like peptide ligand, bacteria extracellular trap (BET) peptide, with modular design composed of targeting, assembly, and hydrophobic motifs with an aggregation-induced emission feature...

Gamma secretase (GS) is an important therapeutic target in anticancer drug discovery. Increased GS activity activates notch signaling pathway which is associated with cancer stemness and drug resistance in cancer cells. A total of 69,075 natural and their derivative compounds were screened to identify the lead compound on the basis of in silico GS catalytic domain binding potential and in vitro selective anticancer efficacy. STOCK1N-23234 showed higher dock score (-11.82) compared to DAPT (-9.2) in molecular docking experiment and formed hydrogen bond with the key amino acid (Asp385) involve in catalysis process...

Tumor heterogeneity remains a significant obstacle in cancer therapy due to diverse cells with varying treatment responses. Cancer stem-like cells (CSCs) contribute significantly to intratumor heterogeneity, characterized by high tumorigenicity and chemoresistance. CSCs reside in the depth of the tumor, possessing low reactive oxygen species (ROS) levels and robust antioxidant defense systems to maintain self-renewal and stemness. A nanotherapeutic strategy is developed using tumor-penetrating peptide iRGD-modified high-density lipoprotein (HDL)-mimetic nanodiscs (IPCND) that ingeniously loaded with pyropheophorbide-a (Ppa), bis (2-hydroxyethyl) disulfide (S-S), and camptothecin (CPT) by synthesizing two amphiphilic drug-conjugated sphingomyelin derivatives...

BACKGROUND: One of the main reasons for cancer resistance to chemotherapy is the presence of cancer stem cells (CSCs) in cancer tissues. It is also believed that CSCs are the unique originators of all tumor cells. On the other hand, the Epithelial-Mesenchymal Transition pathway (EMT) can act as the main agent of metastasis. Therefore, it is possible that targeting CSCs as well as the EMT pathway could help in cancer therapy. Considering that CSCs constitute only a small percentage of the total tumor mass, enrichment before study is necessary...

PURPOSE/OBJECTIVE(S): Early clinical trials have provided evidence for RT-induced systemic effects in conjunction with αPD1 or IL-2 in metastatic patients, but strong abscopal responses are clinically rare. We investigated the effect of a triple combination of CD122-directed IL-2/αIL-2 complexes (IL-2c), hRT, and αPD1 on tumor-specific CD8+ T cell differentiation and the abscopal effect vs. the respective dual treatments. MATERIALS/METHODS: Mice bearing bilateral tumors were treated with two fractions of 8 Gy (C51 colon carcinoma model) or 12 Gy (B16 melanoma model); αPD1 was given weekly; IL-2c was given for five consecutive days...

Colorectal cancers are one of the leading cancers worldwide and are known for their high potential for metastasis and resistance to therapy. The aim of this study was to investigate the effect of various combination therapies of irinotecan with melatonin, wogonin, and celastrol on drug-sensitive colon cancer cells (LOVO cell line) and doxorubicin-resistant colon cancer stem-like cells (LOVO/DX cell subline). Melatonin is a hormone synthesized in the pineal gland and is responsible for circadian rhythm. Wogonin and celastrol are natural compounds previously used in traditional Chinese medicine...

Glioblastoma (GBM) is the most common and aggressive type of brain tumor due to its elevated recurrence following treatments. This is mainly mediated by a subpopulation of cells with stemness traits termed glioblastoma stem-like cells (GSCs), which are extremely resistant to anti-neoplastic drugs. Thus, an advancement in the understanding of the molecular processes underlying GSC occurrence should contribute significantly towards progress in reducing aggressiveness. High levels of endothelin-converting enzyme-1 (ECE1), key for endothelin-1 (ET-1) peptide activation, have been linked to the malignant progression of GBM...

Background: Clostridioides difficile ( C. difficile ) is the primary cause of healthcare-associated infectious diarrhea. Pediatric patients with oncology and stem cell transplant (SCT) diagnoses are at greater risk of C. difficile infections (CDI) and C. difficile colonization than those without. Misdiagnosis of C. difficile colonization as infection and subsequent unnecessary treatment can lead to antibiotic resistance, increased healthcare costs, and an overestimation of CDI rates. Methods: A best practice advisory (BPA) was built into the electronic medical record to guide decision making regarding clinically indicated C...

K-Ras is a well-studied oncogene, and its mutation is frequently found in epithelial cancers like pancreas, lung, and colorectal cancers. Cancer cells harboring K-Ras mutations are difficult to treat due to the drug resistance and metastasis properties. Cancer stem cells (CSCs) are believed the major cause of chemotherapeutic resistance and responsible for tumor recurrence and metastasis. But how K-Ras mutation affects CSCs and inflammation is not clear. Here, we compared two colon cancer cell lines, HCT-116 and HT-29, with the former being K-RasG13D mutant and the latter being wildtype...

According to the global cancer burden data for 2020 issued by the World Health Organization (WHO), colorectal cancer has risen to be the third-most frequent cancer globally after breast and lung cancer. Despite advances in surgical treatment and chemoradiotherapy for colon cancer, individuals with extensive liver metastases still have depressing prognoses. Numerous studies suggest ZFPs are crucial to the development of colon cancer. The ZFP family is encoded by more than 2% of the human genome sequence and is the largest transcriptional family, all with finger-like structural domains that could combine with Zn2+ ...

PURPOSE: Ecotropic viral integration site 1 (EVI1) is an oncogenic transcription factor that has been attributed to chemotherapy resistance in different cancers. As yet, however, its role in colon cancer drug resistance is not completely understood. Here, we set out to investigate the functional and therapeutic relevance of EVI1 in colon cancer drug resistance. METHODS: The EVI1 gene was knocked down in colon cancer cells that were subsequently tested for susceptibility to irinotecan using in vitro assays and in vivo subcutaneous mouse colon cancer models...

Androgen deprivation therapy (ADT) is the standard of care treatment for advance stage prostate cancer. Treatment with ADT develops resistance in multiple ways leading to the development of castration-resistant prostate cancer (CRPC). Present research establishes that prostate cancer stem-like cells (CSCs) play a central role in the development of treatment resistance followed by disease progression. Prostate CSCs are capable of self-renewal, differentiation, and regenerating tumor heterogeneity. The stemness properties in prostate CSCs arise due to various factors such as androgen receptor mutation and variants, epigenetic and genetic modifications leading to alteration in the tumor microenvironment, changes in ATP-binding cassette (ABC) transporters, and adaptations in molecular signaling pathways...

We aimed to analyze rates and risk factors for carbapenemase-producing Enterobacterales (CPE) bloodstream infection (BSI) in CPE-colonized patients with malignancies or following hematopoietic cell transplantation. We retrospectively collected data on demography, underlying disease, colonizing CPE, treatment, intensive care unit (ICU) hospitalization, CPE-BSI, and mortality in CPE-colonized immunocompromised patients (2014-2020). Two hundred twenty-one patients were colonized with 272 CPE: 254 (93.4%) carried one carbapenemase [KPC (50...

Metastatic colorectal cancer (CRC) remains a hard-to-cure neoplasm worldwide. Its curability declines with successive lines of treatment due to the development of various cancer resistance mechanisms and the presence of colorectal cancer stem cells (CSCs). Celastrol and resveratrol are very promising phytochemicals for colon cancer therapy, owing to their pleiotropic activity that enables them to interact with various biological targets. In the present study, the anticancer activities of both compounds were investigated in metastatic colon cancer cells (LoVo cells) and cancer stem-like cells (LoVo/DX)...

INTRODUCTION: Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States. There have been improvements in screening, and therefore overall survival, but patients continue to present at late stages when minimal treatment options are available to them. While some targeted therapies have been introduced, their application is limited by patient-specific tumor characteristics. Additional targets for CRC in patients who present at a late stage, or who experience tumor relapse, need to be identified to continue to improve patient outcomes...

The aim of the present work was to evaluate the in vitro effect of Manuka honey and its combination with 5-Fu, the most common drug used in the treatment of colon cancer, on the morphological and physical parameters of colonspheres enriched with cancer stem-like cells deriving from HCT-116 colon adenocarcinoma cell line and on the apoptosis rate. Manuka honey, alone and more in combination with 5-Fu, reduced the weight, the diameter and mass density of the spheroids and induced apoptosis through the downregulation of many apoptosis inhibitors, including IAPs (Livin, Survivin, XIAP), IGFs (IGF-I, IGF-II and IGF-IR) and HSPs (HSP-27, HSP-60 and HSP-70)...

BACKGROUND: Despite advances in chemotherapies and targeted drugs, colorectal cancer (CRC) remains challenging to treat due to drug resistance. Emerging evidence indicates that cancer-associated fibroblasts (CAFs) facilitate the generation of cancer stem-like cells (CSCs) and drug resistance. Glycogen synthase kinase-3 (GSK) associated signaling pathways have been implicated in the generation of CSCs and represent a target for therapeutics development. HYPOTHESIS: Gamma-mangostin (gMG) isolated from Garcinia mangostana was evaluated for its ability to downregulate GSK3β-associated signaling in CRC cells and overcome CAF-induced 5-fluorouracil resistance and CSC generation...

The mechanical phenotype of cells is an intrinsic property of individual cells. In fact, this property could serve as a label-free, non-destructive, diagnostic marker of the state of cells owing to its remarkable translational potential. A microfluidic device is a strong candidate for meeting the demand of this translational research as it can be used to diagnose a large population of cells at a single cell level in a high-throughput manner, without the need for off-line pretreatment operations. In this study, we investigated the mechanical phenotype of the human colon adenocarcinoma cell, HT29, which is known to be a heterogeneous cell line with both multipotency and self-renewal abilities...

Colorectal carcinoma (CRC) remains a huge challenge in clinical treatment due to tumor metastasis and recurrence. Stem cell-like colon tumor-repopulating cells (TRCs) are a subpopulation of cancer cells with highly tumorigenic and chemotherapy resistant properties. The core transcription factor c-Myc is essential for maintaining cancer stem-like cell phenotypes, yet its roles and regulatory mechanisms remain unclear in colon TRCs. We report that elevated c-Myc protein supported formation and growth of TRC spheroids...

Colorectal cancer is the third most common cancer worldwide. Cancer stem cells are known to play an important role in relapse, and metastases of the disease after chemotherapy. Investigation of new drugs, and their combinations targeting these cells and thus eliminating cancer is one of the most urgent needs of today's chemotherapy. The aim of the present study was to evaluate the effects of Bryophytes like Abietinella abietina (AA), Homolothecium sericeum (HS), Tortella tortuosa (TT), Syntrichia ruralis (SR), and Bryoerythrophyllum rubrum (BR) species extracted with ethyl alcohol on 5-fluorouracil(5-FU) resistant colorectal cancer cell lines (HCT116 and HT29)...