Prognostic value of p53 protein and MK-1 (a tumor-associated antigen) expression in gastric carcinoma

Background MK-1, the target molecule of FU-MK-1, is encoded by the GA733-2 gene, which is currently being used as a target in clinical trials for gastric, intestinal and biliary cancer treatment with monoclonal antibodies. Also of interest is p53, a protein that has been intensively investigated in relation to particular types of tumors, patterns of metastases, tumor stage, and prognosis. Methods The expression of p53 protein and MK-1 antigen was investigated in specimens from 42 patients with gastric carcinoma. The specimens were stained by the avidin-biotin peroxidase technique for immunohistochemical examination. Results MK-1 was positive in 21 (50%) of the 42 cases. MK-1 expression was more frequent in cardia tumors (71%), in large (>3 cm) tumors (60%–64%), and in specimens from patients with more than five metastatic lymph nodes (69%). p53 expression was present in 20 (48%) of the 42 cases. Of these 20 patients, 15 (52%) had tubular adenocarcinoma (TA) and 5 (38%) had signet ring cell carcinoma. p53 expression was more frequent in the tumors of male patients (55% vs 27%); in poorly differentiated TAs (60% vs 47% in well-to-moderately differentiated TAs); in smaller tumors (￡3 cm, 72% vs 43%–50% in larger tumors); in patients with a prominent inflammatory response (61% vs 21%; P < 0.02); and in patients with lymphatic vessel invasion (77% vs 34%; P < 0.02). However, p53 expression was less frequent in the presence of more than five metastatic lymph nodes (23% vs 60% for five or fewer nodes; P < 0.05). Most patients with p53- and MK-1-positive gastric carcinomas and those more than five metastatic lymph nodes had a poor prognosis. Conclusion The study found that the expression of both p53 and MK-1 was frequent in aggressive gastric carcinomas; however, extensive lymph node involvement (more than five nodes) was the only significant factor related to overall survival.     

Serological evaluation of 52 children immunized with the combined measles, mumps and rubella vaccine.

Fifty-two of 298 children vaccinated with the measles-mumps-rubella (MMR) vaccine at around the age of 16 months were evaluated for antibody titres against measles, mumps, and rubella. The seropositivity rates for measles, mumps, and rubella were 86%, 92%, and 98%, respectively. While the most prominent side effects were irritability (6.04%) and fever (4.69%), 83.55% of the vaccinated children showed no undesirable reaction to the vaccine. The MMR vaccine appeared to be immunogenic and nonreactogenic for the children in the study.     

Simultaneous occurrence of papillary intrafollicular and microcarcinomas with bilateral medullary microcarcinoma of the thyroid in a patient with multiple endocrine neoplasia type 2A: report of a case

We report the case of a simultaneous occurrence of papillary intrafollicular and microcarcinomas with bilateral medullary microcarcinoma of the thyroid in a patient with multiple endocrine neoplasia type 2A. The concurrent presence of two thyroid carcinomas is rare. The simultaneous occurrence of two different tumors in the same thyroid each being multifocal and smaller than 1 cm in diameter has not been previously reported in the literature. Furthermore, we define the first case of intrafollicular papillary thyroid carcinoma (carcinoma in situ). Received: June 11, 2001 / Accepted: January 8, 2002     

Mutations in human complement regulator, membrane cofactor protein (CD46), predispose to development of familial hemolytic uremic syndrome

Membrane cofactor protein (MCP; CD46) is a widely expressed transmembrane complement regulator. Like factor H it inhibits complement activation by regulating C3b deposition on targets. Factor H mutations occur in 10-20% of patients with hemolytic uremic syndrome (HUS). We hypothesized that MCP mutations could predispose to HUS, and we sequenced MCP coding exons in affected individuals from 30 families. MCP mutations were detected in affected individuals of three families: a deletion of two amino acids (D237/S238) in family 1 (heterozygous) and a substitution, S206P, in families 2 (heterozygous) and 3 (homozygous). We evaluated protein expression and function in peripheral blood mononuclear cells from these individuals. An individual with the D237/S238 deletion had reduced MCP levels and approximately 50% C3b binding compared with normal controls. Individuals with the S206P change expressed normal quantities of protein, but demonstrated approximately 50% reduction in C3b binding in heterozygotes and complete lack of C3b binding in homozygotes. MCP expression and function was evaluated in transfectants reproducing these mutations. The deletion mutant was retained intracellularly. S206P protein was expressed on the cell surface but had a reduced ability to prevent complement activation, consistent with its reduced C3b binding and cofactor activity. This study presents further evidence that complement dysregulation predisposes to development of thrombotic microangiopathy and that screening patients for such defects could provide informed treatment strategies.     

Rectal washout with cytotoxic solution can be extended to the whole colon

BACKGROUND: Rectal irrigation with a cytotoxic agent does not kill viable intraluminal cancer cells proximal to the primary tumour. To prevent implantation of these cells at the time of restorative proctectomy, the feasibility of retrograde whole-colon irrigation just before surgery was explored. METHODS: The cytotoxic efficacy of different combinations of povidone-iodine (PVPI) and Gastrografin was tested with the trypan blue exclusion test on a human colon carcinoma cell line (SW620) in vitro. Subsequently, a retrograde whole-colon lavage with PVPI 5 per cent and Gastrografin 12 per cent was performed in 14 euthyroid, non-allergic patients with colorectal cancer using a colostomy irrigation set. Thyroid function and mucosal damage were assessed. RESULTS: It took 2 min and approximately 1 litre of infused solution to reach the caecum in all patients. The solution was 100 per cent tumoricidal in vitro and remained so after colonic irrigation. Total serum tri-iodothyronine (T3) levels decreased and those of reverse T3 increased, but normalized after 1 week. Superficial epithelial desquamation was observed shortly after irrigation; however, complete restoration occurred within 7 days. CONCLUSION: A rectal washout can easily be extended to a retrograde irrigation of the whole colon in elective colorectal cancer surgery. This may help to prevent anastomotic and local recurrence due to implantation of viable exfoliated tumour cells.     

Bone sialoprotein-induced reparative dentinogenesis in the pulp of rat’s molar

Bone sialoprotein (BSP), an osteogenic protein (OP), mixed with a carrier, was implanted in the pulp of rat first upper molars (OP group). Cavities were prepared with dental burs and pulp perforation was carried out by pressure with the tip of a steel probe. After 8, 14, and 30 days, the rats were killed and the pulps of the OP group were compared with (1) a sham group (S group), (2) a group where the carrier was implanted alone (C group), and (3) capping with calcium hydroxide (Ca group). After 8 days, a few inflammatory cells were seen, mostly located at the pulp surface near the perforation. In the Ca group, a dentin bridge started to form, in contrast to the other groups. After 15 days, globular structures were seen in the pulps of the S and C groups. A reparative osteodentin bridge isolated the pulp from the cavity in the Ca group. Variable reactions were seen in the OP group, with some evidence of cell and matrix alignments or plugs of osteodentin in continuity with an inner layer of reparative dentin. After 30 days, irregular osteodentin formation was observed in the pulps of the S and C groups, with a tendency for globular structures to merge, but with interglobular spaces filled by pulp remnants. In the Ca group, osteodentin was observed in the mesial part of the pulp chamber. In the BSP-implanted group, the osteogenic protein stimulated the formation of a homogeneous dentin-like deposit occupying most of the mesial part of the pulp. Apparently, BSP stimulates the differentiation of cells which secrete an organized extracellular matrix more efficiently than any other capping material used so far. Altogether, the results reported here support that bone sialoprotein displays novel bioactive properties and is capable of stimulating in 1 month’s time the development of a thick reparative dentinal tissue in the pulp, occluding the perforation and filling the mesial third of the pulp chamber. Received: 13 October 1999 / Accepted: 6 December 1999     

Cholelithiasis in cervico-oculo-acoustic (Wildervanck's) syndrome

An unusual case of cholelithiasis in an 18–month-old boy with cervico-oculo-acoustic (Wildervanck's) syndrome is presented. Our patient had Duane's retraction syndrome, Klippel-Feil anomaly and congenital deafness. To our knowledge this is the first case in which a probable association between cholelithiasis and Wildervanck's syndrome has been recorded. On the other hand, the presence of mutual malformations and anomalies such as scoliosis, ventricular septal defect, ectopic kidney, hydrocephalus, hypoplastic thumb and growth retardation seems to suggest that Wildervanck's syndrome is a clinical variant of Klippel-Feil sequence.     

Phase II study of gemcitabine plus paclitaxel in metastatic breast cancer patients with prior anthracycline exposure

Chemotherapy provides palliation and modest prolongation of symptom-free survival in metastatic breast cancer. Taxane containing regimens are commonly considered to be among the initials in metastatic setting due to earlier use of anthracyclines in the course of breast cancer. Therefore, we conducted this Phase II study to assess efficacy and safety of gemcitabine plus paclitaxel (GT) combination therapy in anthracycline pretreated metastatic first-line setting. Patients and Methods: The study enrolled 26 women with pathologically confirmed and measurable metastatic breast cancer who were previously treated with anthracycline but no prior chemotherapy for metastatic disease. Twenty six and twenty four patients were eligible for toxicity and efficacy evaluations respectively. Mean age was 47.3 years and median ECOG performance status was 0. Twenty patients (76.9 percent) had visceral metastases, most commonly located in liver and lung. Treatment schedule was as follows: paclitaxel 175 mg/m² was administered intravenously in 3 hours on Day 1 and gemcitabine 1000 mg/m² was administered intravenously in 30 minutes on Day 1 after paclitaxel application, and on Day 8 every 21 days. Results: Objective response rate was 41.7 percent (95 percent CI: 21.9-61.4) with 16.7 percent (95 percent CI: 1.7-31.6 percent) CR, and 25.0 percent (95 percent CI: 7.6-42.3 percent) PR. Median time to progression and overall survival were 9.6 and 14.5 months, respectively. Grade 3-4 toxicity was observed in 34.6 percent (9) patients. Treatment of two patients was discontinued due to toxicity, consisting of Grade 3 hypersensitivity reactions and Grade 4 infections in one patient each. Dose reductions due to myelotoxicity were performed in 4 (15.3 percent) patients. Hematologic toxicities were generally manageable with appropriate dose modifications and supportive care. Conclusion: Gemcitabine and paclitaxel combination regimen is effective and has manageable toxicity profile as first line metastatic setting.