OBJECTIVES To analyse the diagnosis and treatment of 24 hereditary nonpolyposis colorectal cancer (HNPCC) kindreds and report mismatch repair gene mutations. METHODS The diagnosis, treatment and follow-up of 24 HNPCC kindreds were reviewed retrospectively, cancer incidence and spectrum were recorded. Clinical characteristics and treatment were analyzed. Peripherial blood and genomic DNA were extracted from family members who had provided informed consent. PCR and SSCP were used to screen coding regions of the hMLH1 and hMSH2 genes. Variant bands were sequenced by 377 DNA sequencer after purification. RESULTS One hundred and 25 malignant neoplasms were diagnosed in 75 patients (multiple cancers in 24) with an average age of 51 years in 24 pedigrees. The onset of the disease occurred earlier than expected with the passing of each generation within large kindreds. The neoplasm mainly included colonic cancer (63 patients), rectal cancer(21), stomach cancer(13), endometric cancer(7), and esophageal cancers(6). 84% patients received radical operations. Of 64 patients with colorectal cancer 16 had metachronous colorectal cancer. 24% colorectal patients developed metachronous cancer within 10 years after initial operation and received re-operation. In 3 detected families with germline hMSH2 and hMLH1 mutations resulting in truncated protein, 12 carriers were found. CONCLUSIONS The main characteristics of hereditary nonpolyposis colorectal cancer include early onset and frequence of cancer; predominance of colorectal cancer, especially right-sided colonic cancer; frequency of multiple primary cancer, especially colorectal cancer; and age anticipation in large HNPCC pedigrees. Segmental resection of colorectal cancer is not suitable for colorectal cancer patient in HNPCC kindred. Intensive follow-up is important for all patients and possible gene carriers.
Adaptor Proteins, Signal Transducing ; Adult ; Aged ; Carrier Proteins ; Colorectal Neoplasms, Hereditary Nonpolyposis ; diagnosis ; genetics ; therapy ; DNA-Binding Proteins ; Female ; Humans ; Male ; Middle Aged ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein ; Mutation ; Neoplasm Proteins ; genetics ; Nuclear Proteins ; Proto-Oncogene Proteins ; genetics

OBJECTIVE:To optimize the formulation of ferulic acid ligustrazine (FATM) solid lipid nanoparticles (FATM-SLN),and conduct the quality evaluation. METHODS:Emulsification ultrasonic method was used to prepare FATM-SLN. Using particle size and entrapment efficiency as indexes,amount of glyceryl monostearate,egg yolk lecithin (PC),poloxamer 188 (P188),and sodium stearate as factors,single factor test and orthogonal test were used to optimize the formulation;and verifica-tion test was conducted. The appearance morphology,distribution of particle size,Zeta potential,stability and in vitro release de-gree of prepared FATM-SLN were investigated. RESULTS:The optimal formulation was as follows as FATM of 10 mg,glyceryl monostearate of 300 mg,PC of 200 mg,P188 of 200 mg,sodium stearate of 10 mg,and purified water of 20 mL. The prepared FATM-SLN showed spherical solid particles,appearance morphology was round,distribution of particle size was 40-800 nm,parti-cle size was 106.23 nm,polydispersity index was 0.254,Zeta potential was -34.8 mV,entrapment efficiency was 73.32%,drug loading was 1.20%;the appearance had no obvious changes within 10 d in 4 ℃(RSD<2%). The drug-release in 0.5-1 h was the fastest,the cumulative release degree reached to 60.47%;it tended to be stable after 8 h,the cumulative release degree reached to 93.46%,and drugs were basically released completely. CONCLUSIONS:FATM-SLN formulation is successfully optimized,and the prepared FATM-SLN has small particle size,high entrapment efficiency and good stability.