Resistance to chemotherapy and molecularly targeted therapies is a major problem facing current cancer research. The mechanisms of resistance to 'classical' cytotoxic chemotherapeutics and to therapies that are designed to be selective for specific molecular targets share many features, such as alterations in the drug target, activation of prosurvival pathways and ineffective induction of cell death. With the increasing arsenal of anticancer agents, improving preclinical models and the advent of powerful high-throughput screening techniques, there are now unprecedented opportunities to understand and overcome drug resistance through the clinical assessment of rational therapeutic drug combinations and the use of predictive biomarkers to enable patient stratification.

Cancer drug resistance: an evolving paradigm

There has been much effort recently to define the role of adipocytokines, which are soluble mediators derived mainly from adipocytes (fat cells), in the interaction between adipose tissue, inflammation and immunity. The adipocytokines adiponectin and leptin have emerged as the most abundant adipocyte products, thereby redefining adipose tissue as a key component not only of the endocrine system, but also of the immune system. Indeed, as we discuss here, several adipocytokines have a central role in the regulation of insulin resistance, as well as many aspects of inflammation and immunity. Other adipocytokines, such as visfatin, have only recently been identified. Understanding this rapidly growing family of mainly adipocyte-derived mediators might be of importance in the development of new therapies for obesity-associated diseases.

Adipocytokines: mediators linking adipose tissue, inflammation and immunity.

Bevacizumab plus Irinotecan,Fluorouracil,and Leucovorin for Metastatic Colorectal Cancer

Epithelial to mesenchymal transition (EMT) is essential for driving plasticity during development, but is an unintentional behaviour of cells during cancer progression. The EMT-associated reprogramming of cells not only suggests that fundamental changes may occur to several regulatory networks but also that an intimate interplay exists between them. Disturbance of a controlled epithelial balance is triggered by altering several layers of regulation, including the transcriptional and translational machinery, expression of non-coding RNAs, alternative splicing and protein stability.

Regulatory networks defining EMT during cancer initiation and progression

Epidemiology and Natural History of Inflammatory Bowel Diseases

The high prevalence of colorectal neoplasms in preoperative patients with abdominal aortic aneurysm or peripheral artery disease.

We report a case of sigmoido-vesical fistula due to sigmoid diverticulitis. Magnetic resonance imaging enabled us to visualize the fistula itself in the bladder wall. Magnetic resonance imaging was highly effective in making a precise diagnosis and also provided important additional information for the preoperative work-up of the patient.

Preoperative evaluation of enterovesical fistula using magnetic resonance imaging: case report.

Background This study evaluated the difference of postoperative complications according to the radiation technique after preoperative radiotherapy for rectal cancer. Methods Among 224 patients with rectal cancer who underwent preoperative radiotherapy, 159 patients were treated with the 2-portal technique and 65 patients with the 4-portal technique. Comparison was performed between these 2 groups. Results The 5-year disease-free survival and local recurrence rate showed no difference between the 2 groups. There was also no difference in postoperative mortality. However, the 4-portal group had a significantly lower morbidity rate of 36.9% than the 2-portal group of 54.1% ( P = .02). The rate of major complications that needed reoperation was also significantly lower in the 4-portal group (0%) than the 2-portal group (11.9%) ( P = .01). The anastomotic leakage rate was significantly lower in the former (2.8% vs 20.0%, P = .033). Conclusion The 4-portal technique is a better technique than the 2-portal technique for decreasing postoperative complications in preoperative radiotherapy for rectal cancer.

The 4-portal technique decreases adverse effects in preoperative radiotherapy for advanced rectal cancer: comparison between the 2-portal and the 4-portal techniques.

Background: In recent studies a high frequency of microsatellite instability among colorectal cancers in young patients has been reported, but the frequency of microsatellite instability (MSI) and chromosomal instability among colorectal cancers in young patients has not yet been fully elucidated. Only one report showed an increased loss of heterozygosity (LOH) ratio at 9p locus, which harbors tumor suppressor genes p16. The LOH and MSI status among colorectal cancers in young patients was examined. Methods: Twenty-five patients under 40 years of age diagnosed with colorectal cancer were examined for MSI and LOH using 17 microsatellite markers, and also p16 expression patterns were evaluated by immunohistochemistry and methylation status of the p16 gene was assessed by methylation-specific PCR. Results: MSI was observed in only one case (4%). LOH at 2p, 5q, 9p, 11q, 17p, and 18q was observed in 41%, 59%, 42%, 35%, 46%, and 56% of cases, respectively. Eighty-three percent of patients showed p16-positive ex...

Genetic characterization of colorectal cancers in young patients based on chromosomal loss and microsatellite instability

Patients with locally advanced disease can have significant local symptoms. The most common symptoms from local extension are pain, bleeding (hematemesis, melena) and obstruction (dysphagia, vomiting)

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Hirokazu Nagawa

Papers

The high prevalence of colorectal neoplasms in preoperative patients with abdominal aortic aneurysm or peripheral artery disease.

Preoperative evaluation of enterovesical fistula using magnetic resonance imaging: case report.

The 4-portal technique decreases adverse effects in preoperative radiotherapy for advanced rectal cancer: comparison between the 2-portal and the 4-portal techniques.

Genetic characterization of colorectal cancers in young patients based on chromosomal loss and microsatellite instability

Palliative radiation therapy for advanced gastrointestinal cancer.