Tumor-initiating stem cell shapes its microenvironment into an immunosuppressive barrier and pro-tumorigenic niche.

Tumor-initiating stem cells (TSCs) are critical for drug resistance and immune escape. However, the mutual regulations between TSC and tumor microenvironment (TME) remain unclear. Using DNA-label retaining, single-cell RNA sequencing (scRNA-seq), and other approaches, we investigated intestinal adenoma in response to chemoradiotherapy (CRT), thus identifying therapy-resistant TSCs (TrTSCs).

Frequent PIK3CA Mutations in Colorectal and Endometrial Tumors With 2 or More Somatic Mutations in Mismatch Repair Genes.

Background & Aims: Some colorectal and endometrial tumors with microsatellite instability not attributable to MLH1 hypermethylation or germline mutations contain 2 or more somatic mutations in genes encoding mismatch repair (MMR) proteins. We sought to define the molecular phenotype of this newly recognized tumor subtype.

Methods: From 2 prospective studies of the efficacy of screening for Lynch syndrome, we identified patients with colorectal and endometrial tumors who had 2 or more somatic (but not germline) mutations in genes encoding MMR proteins (double somatic).

A randomized, phase II study of the anti-insulin-like growth factor receptor type 1 (IGF-1R) monoclonal antibody robatumumab (SCH 717454) in patients with advanced colorectal cancer.

Overexpression of insulin-like growth factor receptor type 1 (IGF-1R) may promote tumor development and progression in some cancer patients. Our objective was to assess tumor uptake of fluorodeoxyglucose by positron-emission tomography in patients with chemotherapy-refractory colorectal cancer treated with an anti-insulin-like growth factor receptor type 1 (anti-IGF-1R) monoclonal antibody, robatumumab. This was a randomized, open-label study with two periods (P1 and P2).

Phase I adjuvant trial of sorafenib in patients with hepatocellular carcinoma after orthotopic liver transplantation.

Background: Post-transplant hepatocellular carcinoma recurrence has been reported to be between 15-18% and is higher among patients with high-risk features (bilobar tumor, macrovascular invasion, or multifocality). There are no known treatments which reduce risk of recurrence post-transplant. Sorafenib is currently approved for the treatment of advanced hepatocellular carcinoma.

Peripheral blood mononuclear CD133 mRNA levels correlates with response to treatment in patients with gastrointestinal stromal tumors.

Background: CD133 is a marker that identifies/enriches cancer stem cell implicated in tumor initiation. We hypothesize that changes in the CD133 mRNA expression levels and vascular endothelial growth factor (VEGF) may correlate tumor response in GIST.

Methodology/principal Findings: After informed consent, we obtained peripheral blood samples from 24 evaluable patients with gastrointestinal stromal tumors (GIST).

Celecoxib downregulates CD133 expression through inhibition of the Wnt signaling pathway in colon cancer cells.

CD133-positive cancer stem cells in colon cancer are resistant to conventional chemotherapy. The aim of the present study was to investigate the effect of celecoxib, a COX-2 inhibitor, on CD133 expression in HT29 and DLD1 cells. HT29 and DLD1 cells were treated with celecoxib using different concentrations and duration.

A phase 2 trial of ixabepilone plus cetuximab in first-line treatment of metastatic pancreatic cancer.

Background: The aim of this phase 2 study was to evaluate the safety and efficacy of ixabepilone plus cetuximab in patients with advanced pancreatic cancer.

Methods: Eligible patients had advanced pancreatic adenocarcinoma that was metastatic or not amenable to resection, a Karnofsky performance status ≥70%, and no prior therapy for advanced disease. Patients received ixabepilone 32 mg/m(2) (3-hour IV infusion) every 3 weeks and cetuximab 250 mg/m(2) (1-hour IV infusion) weekly.

CD133, Stem Cells, and Cancer Stem Cells: Myth or Reality?

CD133, a member of the prominin family, is found in a variety of tissues with at least three variants. The function of CD133 is not well understood, but its expression is subject to changes in the microenvironment cues including bioenergetic stress. Knockout of CD133 does not affect renewal, but mammary gland branching.

5-Fluorouracil upregulates the activity of Wnt signaling pathway in CD133-positive colon cancer stem-like cells.

Background And Objective: CD133-positive colon cancer stem like cells (CSLCs) are resistant to the conventional cytotoxic drug 5-fluorouracil (5-FU). Wnt signaling pathway plays important roles in colon cancer carcinogenesis and metastasis, and regulates the self-renewal capacity of CSLCs. In the present study, we explored the impact of 5-FU on Wnt signaling pathway of CD133-positive colon CSLCs, and the relation between Wnt signaling pathway and drug resistance of CD133-positive colon CSLCs.

Cancer stem cells, endothelial progenitors, and mesenchymal stem cells: "seed and soil" theory revisited.

Isolation of putative cancer stem cells (CSCs) in various tumors has generated much excitement among researchers who consider these cells the potential "culprits" behind resistance to conventional therapy. Both cancer and cardiovascular disease are believed to be stem cell disorders involving circulating endothelial progenitors (CEPs) and mesenchymal stem cells (MSCs). CD133 and CD44, markers of CSCs in many tumors, also enrich CEPs and MSCs, respectively.

Temporal patterns of fatigue predict pathologic response in patients treated with preoperative chemoradiation therapy for rectal cancer.

Purpose: To investigate whether symptom burden before and during preoperative chemoradiation therapy (CRT) for rectal cancer predicts for pathologic tumor response.

Methods And Materials: Fifty-four patients with T3/T4/N+ rectal cancers were treated on a Phase II trial using preoperative capecitabine and concomitant boost radiotherapy. Symptom burden was prospectively assessed before (baseline) and weekly during CRT by patient self-reported questionnaires, the MD Anderson Symptom Inventory (MDASI), and Brief Fatigue Inventory (BFI).

An Application of Stream Imaging Technique in the Study of Osmotic Behaviors of Multiple Cells.

Light microscopy method offers unique abilities for the determination of membrane transport properties of either single or multiple cells. A stream imaging system composed of a microfluidic device, a charge-coupled device camera, and a microscope has been developed to study the osmotic behavior of multiple cells in response toward their extracellular environment. Cells of interest were first mixed with the desired extracellular medium and streamed into a microchannel.

Elevated circulating endothelial progenitor marker CD133 messenger RNA levels predict colon cancer recurrence.

Background: CD133 is a specific surface marker for bone marrow-derived circulating endothelial progenitors, which are vital in postnatal physiologic and pathologic (eg, tumor) angiogenesis. In this study, the authors examined whether increased levels of expression of CD133 messenger RNA (mRNA) in peripheral blood predicted disease recurrence in patients with colon cancer.

Methods: Semiquantitative real-time reverse transcriptase-polymerase chain reaction analysis was used to quantify CD133 mRNA levels in peripheral blood mononuclear cells from patients with colon cancer.

Conformal radiotherapy of the dominant liver metastasis: a viable strategy for treatment of unresectable chemotherapy refractory colorectal cancer liver metastases.

Objectives: To evaluate the safety and efficacy of conformal radiotherapy (RT) of the dominant liver metastasis as palliative treatment of patients with unresectable colorectal cancer liver metastases.

Methods: We retrospectively reviewed the hospital and RT records of 17 patients with unresectable colorectal liver metastases who had been treated with palliative RT to the dominant liver metastasis at our institution.

Results: The median size of the dominant liver metastasis was 10 cm (range, 3-19 cm).

Preoperative chemoradiotherapy with capecitabine versus protracted infusion 5-fluorouracil for rectal cancer: a matched-pair analysis.

Purpose: To retrospectively compare the acute toxicity, pathologic response, relapse rates, and survival in rectal cancer patients treated with preoperative radiotherapy (RT) and either concurrent capecitabine or concurrent protracted infusion 5-fluorouracil (5-FU).

Methods: Between June 2001 and February 2004, 89 patients with nonmetastatic rectal adenocarcinoma were treated with preoperative RT and concurrent capecitabine, followed by mesorectal excision. These patients were individually matched by clinical T and N stage (as determined by endoscopic ultrasound and CT scans) with 89 control patients treated with preoperative RT and concurrent protracted infusion 5-FU between September 1997 and August 2002.

Phase II study of capecitabine (Xeloda) and concomitant boost radiotherapy in patients with locally advanced rectal cancer.

Purpose: The aim of this study was to determine the efficacy of capecitabine (Xeloda), an oral fluoropyrimidine, as a radiosensitizer in the neoadjuvant treatment of locally advanced rectal cancer (LARC).

Methods And Materials: We conducted a phase II study of capecitabine (825 mg/m2 orally, twice daily continuous) with radiotherapy (52.5 Gy/30 fractions to the primary tumor and perirectal nodes) in 54 patients with LARC (node-negative > or = T3 or any node-positive tumor) staged by endoscopic ultrasound (EUS).

Retrospective study of capecitabine and celecoxib in metastatic colorectal cancer: potential benefits and COX-2 as the common mediator in pain, toxicities and survival?

Objective: COX-2 activation may mediate capecitabine induced toxicities, eg, hand-foot syndrome (HFS) and colorectal cancer progression, both of which may be improved by concurrent celecoxib.

Patients And Methods: From October 2000 to December 2003, 66 patients with metastatic colorectal cancer received concurrent capecitabine at 1000 mg/m/d b.i.

The addition of continuous infusion 5-FU to preoperative radiation therapy increases tumor response, leading to increased sphincter preservation in locally advanced rectal cancer.

Purpose: To compare the outcome from preoperative chemoradiation (CXRT) and from radiation therapy (RT) in the treatment of rectal cancer in two large, single-institutional experiences.

Patients And Methods: Between 1978 and 1995, 403 patients with localized, nonmetastatic, clinically staged T3 or T4 rectal cancer patients were treated with preoperative RT alone at two institutions. Patients at institution 1 (n = 207) were treated with pelvic CXRT exclusively, and patients at institution 2 were treated (except for 8 given CXRT) with pelvic RT alone (n = 196).

Response to preoperative chemoradiation increases the use of sphincter-preserving surgery in patients with locally advanced low rectal carcinoma.

Background: Although controversial, some believe that preoperative chemoradiation increases the use of sphincter-preserving surgery in low rectal carcinoma patients. This article investigates the relationship between objective tumor response and sphincter preservation in low rectal carcinoma patients.

Methods: The authors reviewed the records of 238 patients with T3 or T4 low rectal carcinoma (< or = 6 cm from the anal verge) who underwent preoperative pelvic chemoradiation (45 Gy/25 fractions/5 weeks, n = 182 or 52.