Differentiation of Wharton's jelly mesenchymal stem cells into neurons in alginate scaffold

Alginate scaffold has been considered as an appropriate biomaterial for promoting the differentiation of embryonic stem cells toward neuronal cell lineage. We hypothesized that alginate scaffold is suitable for culturing Wharton's jelly mesenchymal stem cells(WJMSCs) and can promote the differentiation of WJMSCs into neuron-like cells. In this study, we cultured WJMSCs in a three-dimensional scaffold fabricated by 0.25% alginate and 50 m M Ca Cl2 in the presence of neurogenic medium containing 10 μM retinoic acid and 20 ng/m L basic fibroblast growth factor. These cells were also cultured in conventional two-dimensional culture condition in the presence of neurogenic medium as controls. After 10 days, immunofluorescence staining was performed for detecting β-tubulin(marker for WJMSCs-differentiated neuron) and CD271(motor neuron marker). β-Tubulin and CD271 expression levels were significantly greater in the WJMSCs cultured in the three-dimensional alginate scaffold than in the conventional two-dimensional culture condition. These findings suggest that three-dimensional alginate scaffold cell culture system can induce neuronal differentiation of WJMSCs effectively.     

Hepatic resection for metastases of the colon and rectum

Hepatic resection is the treatment of choice for a solitary metastatic deposit from a primary carcinoma of the large intestine in the absence of extrahepatic disease. This study was done to evaluate hepatic resection in the treatment of multiple hepatic metastases from carcinoma of the colon and rectum. Sixty-two patients underwent hepatic resection with an over-all operative mortality of 10 per cent, but a recent (1968-1981) mortality of 2 per cent. Three, five and ten year survival rates were 50, 34 and 21 per cent, respectively. No significant differences in survival patterns were noted comparing site (colon versus rectum), time interval from diagnosis of the primary to diagnosis of metastases (synchronous versus metachronous), sex (male versus female), size of the metastatic lesion (less than 5 centimeters versus greater than or equal to 5 centimeters) or number of metastatic lesions (single versus multiple). The pathologic stage of the primary carcinoma of the large intestine significantly (p less than 0.05) influenced survival patterns after hepatic resection with Dukes' B primary tumor having a median survival time of 123 months versus 27 months for patients with Dukes' C primary tumor. Sixty-seven per cent of those with a recurrence did so within the liver. Adjuvant chemotherapy had no demonstrable effect on survival patterns. Further improvement in survival statistics will require more sensitive staging procedures and effective adjuvant therapy, particularly for patients with Dukes' C primary carcinoma of the large intestine.     

Moist exposed therapy of partial-thickness burn wounds. A multi-center study

Summary In laser-induced partial-thickness burns of pig skin, moist exposed burn ointment (MEBO) produces a moist environment, allows drainage of exudates, reduces eschar formation, and accelerates debridement and wound healing. A prospective multi-center study was conducted to evaluate the effect of MEBO on the healing of partial-thickness burn wounds. We included 52 patients with 100 burn sites ranging from 0.5% to 15% total body surface area in the study. Treatment efficacy was assessed on physical examination of the wound, the course of time of trans-epidermal water loss (TEWL) and moisture values, bacterial wound colonization and the degree of pain experienced by patients during and between dressing changes. Using the Visual Analogue Thermometer device (VAT) a progressive decrease of pain was found throughout the treatment which was statistically significant at 6, 9 and 12 post-burn days. TEWL, as an indicator of re-epithelialization, demonstrated a decreasing trend on day 3, and the reduction became significant from the 6th post-burn day. Moisture was significantly decreased during the first 5 post-burn days. As re-epithelialization progressed there was a net decrease in moisture paralleling TEWL. After 1 week of MEBO treatment, bacterial wound colonization decreased to 10% in the immediate group and to 61% in the late group of application. By the second week, colonization dropped to 5% and 23% respectively. Topical ointment application contributed to the debridement of the wound bed facilitating rapid epithelialization within 2–6 days, depending on the burn depth. MEBO is an ointment that can effectively produce a moist and wet environment for optimal healing of partial-thickness burns.     

Genomic copy number determination in cancer cells from single nucleotide polymorphism microarrays based on quantitative genotyping corrected for aneuploidy

Microarrays are frequently used to profile genome-wide copy number (CN) aberrations. While generally robust for detecting CN variants in germline DNA, the methods used to derive CN from signal intensity values have been suboptimal when applied to cancer genomes. The complexity of genomic aberrations in cancer makes it more difficult to discriminate between signal and noise, and measuring CN as a discrete variable does not account for tumor heterogeneity. Furthermore, standard normalization approaches detect CN changes relative to the overall DNA content, which is often not diploid in cancer. We propose an algorithm that uses the degree of allelic imbalance as well as probe intensity, with a correction for aneuploidy, for a quantitative CN assessment and scoring of allelic ratios. This algorithm results in a more precise definition of CN and allelic aberration in the cancer genome, which is essential for translational efforts focused on using these tools for molecular diagnostics and for the discovery of therapeutic targets.     

Neuroblastomas have distinct genomic DNA profiles that predict clinical phenotype and regional gene expression

Neuroblastoma is a heterogeneous neoplasm that has served as a paradigm for the clinical utility of somatically acquired genomic aberrations. DNA copy number alterations (CNA) are currently used to predict prognosis, including MYCN amplification and deletions at chromosome bands 1p36 and 11q23. We predicted that genome-wide assessment of DNA aberrations in neuroblastoma tumors would provide a more precise estimation of clinical phenotype, and could be used to predict outcome. We measured CNAs in a representative set of 82 diagnostic tumors on a customized high-resolution BAC array-based CGH platform supplemented with additional clones across 1p36, 2p24, 3p21-22, 11q14-24, and 16p12-13, and integrated these data with RNA expression data. We used an unbiased statistical method to define a set of minimal common regions (MCRs) of aberration. Unsupervised hierarchical clustering identified four distinct genomic subclasses. First, a subset of tumors with a clinically benign phenotype showed predominantly whole chromosome gains and losses. Second, tumors with MYCN amplification had a unique genomic signature of 1p deletion and 17q gain, but few other rearrangements. Third, tumors with an aggressive clinical phenotype without MYCN amplification, showed multiple structural rearrangements. Most notable were deletions of 3p, 4p, and 11q and gain of 1q, 2p, 12q, and 17q. Lastly, there was a subset of tumors with an aggressive clinical phenotype and no detectable DNA CNAs. The genomic subsets were highly correlated with patient outcome, and individual MCRs remained prognostic in a multivariable model. DNA signature patterns embed important prognostic information in diagnostic neuroblastoma samples, and can identify candidate cancer-related genes.     

The management of recurrent colorectal cancer

International Journal of Colorectal Disease -     

Resected pulmonary metastases from colorectal cancer

Summary A review of 35 patients who, over an 18-year period, underwent excision of pulmonary metastases from colorectal cancer, is presented. The cumulative five-year survival rate was 22 per cent, and this was significantly increased where the primary colonic cancer was Dukes' A or B. No difference in survival was found regarding the disease-free interval and the number of metastatic lesions. The follow-up of patients with colorectal cancer should always include yearly chest x-rays; and when metastases developed in the lungs alone, surgery for their removal is recommended. Read at the Anglo-American-Australasian meeting of the American Society of Colon and Rectal Surgeons, London, England, June 18, to 20, 1979.     

Self-inflicted sigmoid colon perforation

A rare, if not unique, case of sigmoid colon perforation by a balloon, self-inserted transanally, is described. Mechanical properties of the sigmoid colon make it prone to rupture by pneumatic distention. Management depends on amount of peritoneal contamination, timing, and associated injury. With prompt surgery, isolated traumatic sigmoid colon perforations have a good prognosis.     

Mixed adenoneuroendocrine carcinoma (MANEC) of the gallbladder: A possible stem cell tumor?

A 48 year-old African American woman presented to her physician complaining of a rapidly evolving epigastric and right upper quadrant abdominal pain. A PET-CT of the abdomen and pelvis demonstrated hypermetabolic, polypoid masses within the gallbladder and several tumors in the left lobe of the liver for which she underwent diagnostic laparoscopy. The gallbladder revealed a 3.5 × 3.3 × 2.4 tan-brown exophytic mass located at the fundus and growing into the lumen with multiple contiguous papillary projections arising from the mucosal surface. A concurrent large cell neuroendocrine carcinoma and papillary adenocarcinoma of the gallbladder was revealed histologically. There was shared reactivity to antibodies directed against the distinct antigens for each morphological component with transitional tumor cells (of both histological components) located at the areas where the two tumor types merged, revealing common immunoreactivity for carcinoembryonic antigen, cancer antigen 19-9, keratin 19, c-kit (cluster of differentiation protein 117 (CD117)) and epithelial cell adhesion molecule. Ultrastructurally, individual cells were demonstrated to have overlapping features of neuroendocrine and glandular differentiation. The aforementioned histological, ultrastructural and immunohistochemical profile is strongly suggestive of a biphenotypic stem/progenitor cell tumor of the gallbladder.