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211.
Julia H Carter Larry E Douglass James A Deddens Bruce M Colligan Tejal R Bhatt Jackson O Pemberton Susan Konicek Joanne Hom Mark Marshall Jeremy R Graff 《Clinical cancer research》2004,10(10):3448-3456
PURPOSE: The p21-activated kinase-1 (Pak-1) promotes cell motility and invasiveness. Pak-1 is activated by the Rac, Rho, and Cdc42 small GTPases in response to a variety of stimuli including ras and phosphatidylinositol 3'-kinase/AKT pathway activation. Because Pak-1 plays a central role in regulating cell motility and invasiveness, we sought to determine whether Pak-1 may be involved in the malignant progression of colorectal carcinoma. EXPERIMENTAL DESIGN: Pak-1 expression was examined by immunohistochemistry in archived tissues from normal human colons, tubular and tubulovillous adenomas, invasive adenocarcinomas (stages I-III/IV), and lymph node metastases (184 total specimens from 38 patients). Specific cytoplasmic immunostaining was evaluated for overall intensity and uniformity to derive a combined histoscore (stain intensity x percentage of epithelium stained). RESULTS: Pak-1 expression was increased significantly with colorectal cancer progression from normal tissue to lymph node metastases (P < 0.0001). Furthermore, Pak-1 expression was increased significantly in adenomas, invasive carcinomas, and lymph node metastases compared with normal colon (P < 0.0001). Strikingly, Pak-1 expression was significantly higher in lymph node metastases than in invasive cancers, adenomas, or normal colon (P < 0.0001). Moreover, in patients with multiple lesions representing different stages of disease, Pak-1 expression was increased specifically in the most advanced lesions. CONCLUSIONS: This study demonstrates that Pak-1 expression is increased significantly with malignant progression of human colorectal carcinoma. These data, along with numerous functional studies demonstrating a central role for Pak-1 activity in tumor invasiveness and motility, implicate Pak-1 as an exciting target for therapy of colorectal carcinoma. 相似文献
212.
Licciardone JC Herron KM Marshall MA Woodworth RM 《The Journal of the American Osteopathic Association》2000,100(7):423-4, 427-31
Travel medicine practice in the United States has not been extensively studied. This study included 1078 consecutive patients who presented to a university-based travel medicine clinic from 1990 through 1994. Analyses of patient demographics, clinic attendance, itineraries, and vaccinations were conducted. Mean patient age (+/- SD) was 37.4 +/- 16.2 years; 626 (58.1%) of the patients were male. Travel duration was 103.1 +/- 242.3 days (median, 21 days), and lead time (defined as the time between clinic presentation and departure for the purpose of this study) was 23.8 +/- 26.5 days (median, 16 days). Destination was the strongest independent factor affecting vaccination practices. A lead time of 31 or more days was associated with significantly elevated odds ratios for all immunobiologicals except immune globulin. These findings underscore the need to educate the traveling public, healthcare providers, and the travel industry about the benefits of seeking medical consultation at least 1 month prior to international travel. 相似文献
213.
Schechter DS Marshall R Salmán E Goetz D Davies S Liebowitz MR 《Journal of traumatic stress》2000,13(3):529-534
Objective: Ataque de nervios is a common, self-labeled Hispanic folk diagnosis. It typically describes episodic, dramatic outbursts of negative emotion in response to a stressor, sometimes involving destructive behavior. Dissociation and affective dysregulation during such episodes suggested a link to childhood trauma. We therefore assessed psychiatric diagnoses, history of ataque, and childhood trauma in treatment-seeking Hispanic outpatients (N = 70). Significantly more subjects with an anxiety or affective disorder plus ataque reported a history of physical abuse, sexual abuse, and/or or a substance-abusing caretaker than those with psychiatric disorder but no ataque. In some Hispanic individuals, ataque may represent a culturally sanctioned expression of extreme affect dysregulation associated with childhood trauma. Patients with ataque de nervios should receive a thorough traumatic history assessment. 相似文献
214.
Emerging applications of the tumor necrosis factor family of ligands and receptors in cancer therapy. 总被引:8,自引:0,他引:8
Abnormalities of the tumor necrosis factor (TNF) family members have been linked to several human diseases, including cancer. Novel treatment strategies for cancer are emerging based on an understanding of the function of TNF family members. The advantage of these strategies is their potential to selectively target cancer cells, while sparing normal cells. Combining these new strategies with currently available treatments such as chemotherapy and radiation therapy is under investigation, with promising results. However, because some TNF family members are toxic to normal mammalian cells when administered systemically, only a few TNF family members have potential therapeutic value. This concise review focuses on the clinical implications of four TNF family members for cancer treatment: CD30/CD30 ligand, CD40/CD40 ligand, receptor activator of nuclear factor-kappaB (RANK)/RANK ligand, and TNF-related apoptosis-inducing ligand (TRAIL) Apo-2L/TRAIL receptors. 相似文献
215.
Mary E Reid James R Marshall Denise Roe Michael Lebowitz David Alberts Achyut K Battacharyya Maria Elena Martinez 《Cancer epidemiology, biomarkers & prevention》2003,12(10):1006-1011
Colorectal adenomatous polyps are considered to be the precursor lesion of colorectal cancer (1-3). Greater understanding of the association between smoking and adenoma development enable better detection and prevention of colorectal cancer. This study was conducted in men and women, ages 40-80, participating in a randomized trial testing the effects of wheat bran fiber supplement on adenoma recurrence. First, we investigated smoking exposure (status, cigarettes/day, and years of smoking) and colorectal adenoma characteristics (location, histology, size, and multiplicity) at baseline colonoscopy (n = 1429). Second, we evaluated smoking exposure and adenoma recurrence (n = 1304). The prevalence of distal versus proximal adenomas was greater for < or =30 cigarettes/day [odds ratio (OR), 1.48; 95% CI, 1.02-2.16] and 15 to <25 years of smoking (OR, 1.95; 95% CI, 1.23-3.09) compared with never smokers. Tubular versus villous histology prevalence was increased for > or =30 cigarettes and > or =35 years of smoking (OR, 1.74; 95% CI, 1.21-2.49 and OR, 1.74; 95% CI, 1.24-2.45, respectively) compared with never-smokers. Years of smoking increased prevalence of multiple versus single adenomas, whereas cigarettes/day and years of smoking were associated with large adenomas (> or =1 cm) prevalence as compared with small lesions (< or =0.5 cm). Greater than 35 years of smoking was significantly associated with an increased risk of adenoma recurrence (OR, 1.42; 95% CI, 1.01-1.98). These results suggest that the association between smoking and adenoma prevalence varies by the characteristic of the lesion. Furthermore, the association between smoking and adenoma recurrence is modest and was only significant after a long duration of exposure. Additional investigations that characterize the genetic changes in specific subgroups of prevalent and recurrent adenomas associated with smoking exposure are needed. 相似文献
216.
217.
218.
OBJECTIVE: The purpose of this study was to determine the effect of left-to-right shunting on the resting energy expenditure (REE), total energy expenditure (TEE), and energy intake in a group of 3- to 5-month-old infants with moderate to large unrepaired ventricular septal defects (VSDs) compared with age-matched, healthy infants. METHODS: Eight infants with VSDs and 10 healthy controls between 3 to 5 months of age participated in the study. Indirect calorimetry was used to measure REE and the doubly-labeled water method was used to measure TEE and energy intake. An echocardiogram and anthropometric measurements were performed on all study participants. Daily urine samples were collected at home for 7 days. Samples were analyzed by isotope ratio mass spectrometry. Data were compared using analysis of variance. RESULTS: No significant differences were found in REE (VSD, 42.2 +/- 8.7 kcal/kg/d; control, 43.9 +/- 14.1 kcal/kg/d) or energy intake (VSD, 90.8 +/- 19.9 kcal/kg/d; control, 87.1 +/- 11.7 kcal/kg/d) between the groups. The percent total body water was significantly higher in the VSD infants and the percent fat mass was significantly lower. TEE was 40% higher in the VSD group (VSD, 87.6 +/- 10.8 kcal/kg/d; control, 61.9 +/- 10.3 kcal/kg/d). The difference between TEE and REE, reflecting the energy of activity, was 2.5 times greater in the VSD group. CONCLUSIONS: REE and energy intake are virtually identical between the two groups. Despite this, infants with VSDs have substantially higher TEE than age-matched healthy infants. The large difference between TEE and REE in VSD infants suggests a substantially elevated energy cost of physical activity in these infants. These results demonstrate that, although infants with VSDs may match the energy intake of healthy infants, they are unable to meet their increased energy demands, resulting in growth retardation. 相似文献
219.
Isolation and characterization of propagable cell lines (HUNC) from the androgen-sensitive Dunning R3327H rat prostatic adenocarcinoma 总被引:1,自引:0,他引:1
Presnell SC; Borchert KM; Glover WJ; Gregory CW; Mohler JL; Smith GJ 《Carcinogenesis》1998,19(4):585-590
The Dunning H rat prostate tumor (R3327H) is a widely used experimental
model of human prostatic adenocarcinoma (CaP). The Dunning H tumor has been
characterized as androgen-sensitive, androgen-receptor (AR) positive,
prostate-specific antigen and prostatic acid phosphatase (PAP) positive. To
date, the tumor has been maintained by serial passage in vivo because of
the lack of an in vitro cell line that retains the characteristics of the
in vivo tumor. The objective of the present study was to establish a
propagable cell line from R3327H adenocarcinoma that maintained androgen
sensitivity and expression of AR, PSA and PAP. Tissue harvested from an in
vivo R3327H tumor was dissociated with collagenase and placed into
Richter's improved media (with supplements). A cytokeratin-positive
epithelial cell line (HUNC- E) and a vimentin-positive stromal cell line
(HUNC-S) were generated from the primary culture, subcultured continuously
for >300 days, and passaged >50 times. Survival of the HUNC-E cell
line in vitro depended on several media supplements, including
nicotinamide, insulin, transferrin, selenium and epidermal growth factor
(EGF). HUNC-E cells expressed AR and produced PSA and PAP throughout the
culture period, as confirmed by immunocytochemistry and Western blot
analyses. Addition of 14 nM testosterone (T) or dihydrotestosterone (DHT)
to HUNC-E cells, stimulated DNA synthesis as well as anchorage-independent
growth and PSA production, which demonstrated the androgen-sensitive nature
of the cells in vitro. When HUNC-E and HUNC-S cells were combined in a 3:1
ratio and introduced subcutaneously into syngeneic male hosts, tumors
formed in 2/3 animals with an average latency of 7 months. RT-PCR and
immunocytochemical characterization of the HUNC cell lines revealed that
the cells expressed several growth factors and their cognate receptors,
including HGF, TGF-alpha and the TGF-betas, indicating the establishment of
potential autocrine loops in the neoplastic cells. The HUNC-E and HUNC-S
CaP cell lines, which retain the characteristics of the epithelial and
stromal components of the in vivo R3327H tumor, will allow a more thorough
and informative molecular and biological analysis of prostatic
adenocarcinoma.
相似文献
220.
A study was carried out to find out the effects of prior physical activity, sports participation and prior military training on the incidence of stress fractures among Gentlemen Cadets (GC''s) undergoing military training at Indian Military Academy (IMA). One thousand and fourteen GC''s were followed up for a period of 12 weeks. Thirty-seven GC''s developed stress fractures during the study period. The incidence of stress fractures was significantly higher in GC''s without any prior military training (p=0.0009). They were compared with 100 healthy controls drawn from the study population to study the influence of the other mentioned factors. There was no significant association between prior physical activity and stress fractures (OR=0.74, 95% CL=0.26 to 2.05, p=0.688). There was also no significant relationship between sports participation and stress fractures (OR=0.79. 95% CCL=0.35 to 1.81, p=0.684).KEY WORDS: Risk factors, Stress fractures 相似文献