RESUMO
We report on the preparation of a new type of immunotoxin by conjugation of an epidermal growth factor receptor (EGFR)-binding peptide and an R46E mutation of thermostable direct hemolysin from Grimontia hollisae, (Gh-TDH(R) (46E) /EB). The hybrid immunotoxin was purified to homogeneity and showed a single band with slight slower mobility than that of Gh-TDH(R) (46E) . Cytotoxicity assay of Gh-TDH(R) (46E) /EB on EGFR highly, moderately, low, and non-expressed cells, A431, MDA-MB-231, HeLa, and HEK293 cells, respectively, showed apparent cytotoxicity on A431 and MDA-MB-231 cells but not on HeLa or HEK293 cells. In contrast, no cytotoxicity was observed for these cells treated with either Gh-TDH(R) (46E) or EB alone, indicating enhanced cytotoxic efficacy of Gh-TDH(R) (46E) by the EGFR binding moiety. Further antitumor activity assay of Gh-TDH(R) (46E) /EB in a xenograft model of athymic nude mice showed obvious shrinkage of tumor size and degeneration, necrosis, and lesions of tumor tissues compared to the normal tissues. Therefore, the combination of Gh-TDH(R) (46E) with target affinity agents opens new possibilities for pharmacological treatment of cancers and potentiates the anticancer drug's effect.
Assuntos
Antineoplásicos/farmacologia , Proteínas de Bactérias/farmacologia , Receptores ErbB/genética , Proteínas Hemolisinas/farmacologia , Imunotoxinas/farmacologia , Proteínas Recombinantes/farmacologia , Animais , Proteínas de Bactérias/genética , Toxinas Bacterianas/genética , Toxinas Bacterianas/farmacologia , Linhagem Celular Tumoral , Receptores ErbB/metabolismo , Feminino , Células HEK293 , Células HeLa , Proteínas Hemolisinas/genética , Humanos , Camundongos , Camundongos Nus , Proteínas Recombinantes/genética , Vibrionaceae/genéticaRESUMO
BACKGROUND: Long-term care residents are susceptible to constipation and one-half to three quarter of older nursing home residents receive laxatives regularly. OBJECTIVES: The purpose of this study was to evaluate the factors related to abnormal bowel function and explore the effectiveness of laxative treatment among the elderly residents of a nursing home. PATIENTS AND METHODS: A total of 110 residents older than 65 years old was enrolled in this study. The following variables were gathered: age, gender, body mass index (BMI), length of stay, daily fluid intake, type of food, functional level, cognitive ability, physical therapy status, somatic and psychiatric diseases, number of medications, and medication use. The use and dosage of laxatives were recorded by means of Anatomical Therapeutic Chemical (ATC) classification system. Normal bowel function was defined as defecation frequency from three defecations per day to three defecations per week and stool consistency score of three to five on Bristol Stool Form Scale. A comparison between groups with normal and abnormal bowel function was drawn. RESULTS: Low BMI, increased fluid intake, liquid food intake, poor functional level, poor cognition, and a history of stroke were significantly associated with altered bowel function (P < 0.05). The most frequently used laxatives were glycerol, senna glycoside, and magnesium oxide. There were significant differences in laxative regimens between residents with normal and altered bowel function; those with altered bowel function tended to take more laxatives than those with normal bowel function. CONCLUSIONS: This study suggested that treatment of constipation in the nursing home was unsatisfactory. To improve treatment outcomes in those susceptible to altered bowel function, a coordinated approach with involvement of physicians, nursing staff, and other professionals including dieticians and pharmacists seems necessary.
RESUMO
Intradural disc herniation is rare. In a colon cancer patient who suffered from low back pain for several years, MRI examination showed evidence of vacuum phenomenon and ring enhancement at the level of L3-4. Intradural herniation of an intervertebral disc was confirmed surgically. Pathological evidence of intradiscal gas is rarely reported in the literature, however, an association between intradural disc herniation and pneumocysts was demonstrated in this case. The implications of our sequential radiological and pathological findings for the pathogenesis of intradural pneumocysts are discussed.
