Radiation-induced gastrointestinal (GI) syndrome as a function of age.

Previous studies show increased sensitivity of older mice (28-29 months) compared with young adult mice (3 months, possessing a mature immune system) to radiation-induced GI lethality. Age-dependent lethality was associated with higher levels of apoptotic stem cells in small intestinal crypts that correlated with sphingomyelinase activity, a source of pro-apoptotic ceramide. The objective of this study is to determine whether the cycling crypt base columnar cells (CBCs) in aging animals are specifically more sensitive to radiation effects than the CBCs in young adult mice, and to identify factors that contribute to increased radiosensitivity.

Technical feasibility of salvage endoscopic submucosal dissection after chemoradiation for locally advanced rectal adenocarcinoma.

Background And Aims: The standard treatment of locally advanced rectal cancer is chemoradiation (CRT) followed by proctectomy and adjuvant chemotherapy. However, there is an emerging role for nonsurgical management after CRT or total neoadjuvant therapy (TNT) consisting of CRT and neoadjuvant chemotherapy. Endoscopic submucosal dissection (ESD) after CRT or TNT for rectal cancer, termed "salvage ESD," may be a viable nonsurgical option for carefully selected patients.

Value of adding dynamic contrast-enhanced MRI visual assessment to conventional MRI and clinical assessment in the diagnosis of complete tumour response to chemoradiotherapy for rectal cancer.

Purpose: To determine if DCE-MRI adds diagnostic value to the combined use of T2WI and DWI-MRI in the determination of clinical complete response (cCR) after neoadjuvant treatment (NAT) in patients with locally advanced rectal cancer.

Methods And Materials: In this IRB-approved, HIPAA-compliant retrospective study, response was assessed using a 5-point confidence score by T2WI and DWI-MRI only ('standard MRI'), then with addition of DCE-MRI. Review of digital rectal exams and endoscopy notes produced a clinical overall response score.

Recurrent somatic mutation of FAT1 in multiple human cancers leads to aberrant Wnt activation.

Aberrant Wnt signaling can drive cancer development. In many cancer types, the genetic basis of Wnt pathway activation remains incompletely understood. Here, we report recurrent somatic mutations of the Drosophila melanogaster tumor suppressor-related gene FAT1 in glioblastoma (20.

Response to neoadjuvant therapy in patients with early age-of-onset rectal cancer.

Background: The incidence of rectal cancer in patients ≤ 50 years of age is increasing. The response to neoadjuvant treatment in patients ≤ 50 years of age is not known. Factors affecting the response to neoadjuvant therapy in this age group have not been evaluated.

Reassessing the need for primary tumor surgery in unresectable metastatic colorectal cancer: overview and perspective.

In the absence of symptoms, primary tumor resection in patients who present with unresectable metastatic colorectal cancer is of uncertain benefit. Prophylactic surgery has been traditionally considered in this setting in order to prevent subsequent complications of perforation, obstruction, or bleeding later during the treatment course, which may require urgent surgery associated with higher mortality. However, recent data have called into question the efficacy of this upfront surgical strategy.

Outcome of primary tumor in patients with synchronous stage IV colorectal cancer receiving combination chemotherapy without surgery as initial treatment.

Purpose: The purpose of this study was to describe the frequency of interventions necessary to palliate the intact primary tumor in patients who present with synchronous, stage IV colorectal cancer (CRC) and who receive up-front modern combination chemotherapy without prophylactic surgery.

Patients And Methods: By using a prospective institutional database, we identified 233 consecutive patients from 2000 through 2006 with synchronous metastatic CRC and an unresected primary tumor who received oxaliplatin- or irinotecan-based, triple-drug chemotherapy (infusional fluorouracil, leucovorin, and oxaliplatin; bolus fluorouracil, leucovorin, and irinotecan; or fluorouracil, leucovorin, and irinotecan) with or without bevacizumab as their initial treatment. The incidence of subsequent use of surgery, radiotherapy, and/or endoluminal stenting to manage primary tumor complications was recorded.

Expression of L1-CAM and ADAM10 in human colon cancer cells induces metastasis.

L1-CAM, a neuronal cell adhesion receptor, is also expressed in a variety of cancer cells. Recent studies identified L1-CAM as a target gene of beta-catenin-T-cell factor (TCF) signaling expressed at the invasive front of human colon cancer tissue. We found that L1-CAM expression in colon cancer cells lacking L1-CAM confers metastatic capacity, and mice injected in their spleen with such cells form liver metastases.

Squamous-cell carcinoma of the rectum: a rare but curable tumor.

Purpose: This study was designed to evaluate one institution's experience with treatment outcomes for rectal squamous-cell carcinoma.

Methods: Using our prospective Colorectal Database, we identified patients diagnosed with rectal squamous-cell carcinoma at our institution between 1983 and 2005. Pathology was rereviewed, tumor immunophenotype was compared to control cases of anal squamous-cell carcinoma and rectal adenocarcinoma, treatment modalities and outcomes were analyzed.

GROalpha is highly expressed in adenocarcinoma of the colon and down-regulates fibulin-1.

Purpose: The growth-related oncogene alpha (GROalpha) is a secreted interleukin-like molecule that interacts with the CXCR2 G-protein-coupled receptor. We found that the mRNA and protein products of GROalpha are more highly expressed in neoplastic than normal colon epithelium, and we studied potential mechanisms by which GROalpha may contribute to tumor initiation or growth.

Experimental Design: Cell lines that constitutively overexpress GROalpha were tested for growth rate, focus formation, and tumor formation in a xenograft model.

Assessing the predictive value of clinical complete response to neoadjuvant therapy for rectal cancer: an analysis of 488 patients.

Background: Patients with transmural or node-positive rectal cancer benefit from the addition of chemoradiation to surgical resection. Administration of the chemoradiation (combined modality therapy) preoperatively has gained popularity in recent years. Some patients undergo apparent complete tumor regression after preoperative combined modality therapy, and controversy exists about the proper management of these patients.