In silico identification and microarray analysis of human mucin-like genes

Mucins, which are highly O-glycosylated proteins, are involved in a variety of diseases. Most of the known mucins show little sequence conservation. To identify novel candidate mucins that might be helpful for diagnosis and therapy of diseases, bioinformatics approaches other than homology searches are required. We have developed two bioinformatics approaches that focus on either the amino acid compositions or the repeated sequences in regions carrying 0-linked glycans. Both approaches identify candidate mucins efficiently from the human reference sequence database. The former and latter approaches identified three and two novel mucin-like genes, respectively. We used Affymetrix GeneChip oligonucleotide microarrays to analyze the mucins identified from the database and found that three human mucin genes differed significantly in expression between normal tissues/cells and cancer cell lines. A combination of our bioinformatics approaches and the oligonucleotide microarray method will be useful for the efficient identification of candidate human mucins. Further study of the mucins in cancer tissues will facilitate the direct evaluation of their potential for cancer diagnosis and therapy

Protocol of a pilot randomized clinical trial to evaluate nutritional support and rehabilitation on prevention of skeletal muscle mass loss during neoadjuvant chemotherapy in patients with esophageal cancer.

BackgroundSubtotal esophagectomy with lymph node dissection followed by neoadjuvant chemotherapy (NAC) is the standard treatment for stage II-III esophageal cancer. Esophagectomy is still associated with high morbidity rates, and reducing these rates remains challenging. Among several complications, postoperative pneumonia (PP) is sometimes fatal, which has been reportedly caused by sarcopenia. Thus, nutritional support and rehabilitation may be promising for preventing skeletal muscle mass loss and reduce the incidence of PP.MethodsThis single-center, randomized, open-label, pilot trial will randomize a total of 40 patients with esophageal cancer in a 1:1 ratio either to ISOCAL Clear + rehabilitation arm or only rehabilitation arm. Although all patients will be educated about rehabilitation by a specialized physician and will be asked to undergo the prespecified rehabilitation program, patients treated with ISOCAL Clear + rehabilitation arm will be supplemented by 400 mL of ISOCAL Clear (Nestlé Japan Ltd, Tokyo, Japan) per day during two courses of NAC with docetaxel, cisplatin, and fluorouracil. Body composition will be assessed using Inbody (Inbody Co., Ltd., Tokyo, Japan) just before starting NAC and surgery. The primary endpoint is the change of skeletal muscle index (SMI) during NAC. Secondary endpoints include (i) body weight, total skeletal muscle mass, appendicular skeletal muscle mass, and lean body mass index changes; (ii) the percentage of ISOCAL Clear continuation; (iii) appetite evaluation; (iv) the percentage of targeted calorie achievement; (v) adverse events of NAC; (vi) postoperative complication rates; and (vii) postoperative hospital stay.DiscussionThis prospective trial assesses the efficacy of nutritional support in addition to rehabilitation during NAC for patients with esophageal cancer. The results will be utilized in assessing whether the effects of nutritional support by ISOCAL Clear are promising or not and in planning future larger clinical trials