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101.
102.
L R Lipton V Johnson C Cummings S Fisher P Risby A T Eftekhar Sadat T Cranston L Izatt P Sasieni S V Hodgson H J W Thomas I P M Tomlinson 《Journal of clinical oncology》2004,22(24):4934-4943
PURPOSE: Hereditary nonpolyposis colon cancer (HNPCC) is a Mendelian dominant syndrome of bowel, endometrial, and other cancers and results from germline mutations in mismatch repair (MMR) genes. HNPCC is now best diagnosed on molecular grounds using MMR mutation screening, aided by microsatellite instability (MSI) and immunohistochemistry in tumors. Selection of families for molecular investigation of HNPCC is usually based on suboptimal methods (Amsterdam Criteria or Bethesda Guidelines), but these can be improved using additional clinical data (mean ages of affected persons and presence of endometrial cancer) in a quantitative model. METHODS: We have verified the performance of the Wijnen model and have shown that it remains valid when HNPCC is diagnosed using mutation screening, MSI, and immunohistochemistry. We have also set up and verified our own models (Amsterdam-plus and Alternative), which perform at least as well as the Wijnen model. RESULTS: The Amsterdam-plus model improves on the Amsterdam Criteria by using five extra variables (numbers of colorectal and endometrial cancers in the family, number of patients with five or more adenomas, number with more than one primary cancer of the colorectum or endometrium, and mean age of presentation) and performs better than the Wijnen model. The Alternative model avoids the need to evaluate the Amsterdam Criteria and performs nearly as well as the other models. CONCLUSION: We believe that a quantitative model, such as the Amsterdam-plus model, should be the first choice for selecting families or patients for evaluation of HNPCC using molecular tests. We present an algorithm for this process. 相似文献
103.
Lymph node mapping has become an integral part of the management of melanoma and breast cancer with regard to both staging and treatment. We report our technique for lymphatic mapping and intraoperative lymphoscintigraphy applied to a patient with penile melanoma. This technique may improve the sensitivity of identifying the sentinel lymph node in patients with malignant penile lesions. 相似文献
104.
Skin cancer is the most common and the most preventable form of cancer. Nonmelanoma skin cancers are associated with cumulative exposure to ultraviolet radiation, while melanoma is associated with intense episodes of ultraviolet exposure resulting in sunburns. Numerous risk factors are associated with the development of skin cancer. These include exposure to ultraviolet radiation; phenotypic factors such as skin type, eye and hair color, tendency to burn and tan, and having freckles and moles; a personal or family history of skin cancer; and occupational sun exposure. Primary prevention behaviors include applying SPF 15+ sunscreen 30 minutes before exposure, reapplying SPF 15+ sunscreen every 11/2 to 2 hours or after swimming or sweating, dressing in protective clothing, using shade, limiting exposure during peak sun hours, and avoiding artificial sources of ultraviolet radiation such as tanning beds. Secondary prevention behaviors include screening and early detection in combination with education on the primary prevention behaviors. Interventions designed to increase sun protective behaviors have resulted in increased knowledge and attitudes, but limited behavior change. And while skin cancer screenings have shown promising results, few studies have a follow-up component. Future studies should focus on developing effective strategies for making sun protective behaviors routine and determining the effectiveness of skin cancer screening. To inform approaches to the prevention and control of skin cancer, this paper will summarize key primary and secondary preventive behaviors, highlight primary and secondary prevention programs, and identify key unanswered questions in the area of skin cancer prevention and control. 相似文献
105.
106.
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
107.
Previous work has shown that sustained increased and decreased cell
proliferation, induced by dietary zinc deficiency and caloric restriction
respectively, influence the course of N- nitrosomethylbenzylamine
(NMBA)-induced esophageal carcinogenesis in rats. The present study
considered whether the increased cell proliferation and esophageal tumor
incidence induced by zinc deficiency are reversed upon zinc replenishment.
Weanling rats were maintained initially on a deficient diet containing 4
p.p.m. zinc. After 5 weeks, carcinogen-treated animals were given six
intragastric doses of NMBA (2 mg/kg twice weekly). Controls were untreated.
After the second NMBA dose, the rats were divided into three dietary
groups. One group was continued on the deficient diet, while the other two
groups were switched to diets containing either 75 or 200 p.p.m. zinc, with
half of the members in each group fed ad libitum and half pair-fed with
deficient rats. NMBA-untreated controls were similarly replenished. At
various time points, esophageal cell proliferation was assessed in five
animals from each group by immunohistochemical detection of cells in S
phase, with in vivo 5-bromo-2'deoxyuridine labeling. At 11 weeks after the
first dose, esophageal tumor incidence was greatly reduced, from 100% in
the deficient group to 26 and 14% respectively in the replenished groups
fed ad libitum 75 and 200 p.p.m. zinc and to 14 and 11% respectively in the
replenished groups pair-fed 75 and 200 p.p.m. zinc. In addition, the number
of tumors per esophagus was reduced from 9.93 +/- 4.25 in deficient rats,
to a range of 0.11 +/- 0.31-0.30 +/- 0.54 in replenished animals. Following
zinc replenishment, esophageal cell proliferation, as measured by labeling
index (LI), the number of labeled cells and the total number of cells, was
markedly decreased in NMBA-untreated and -treated esophagi as compared with
those in corresponding deficient esophagi. Thus, the esophageal cell
proliferation induced by zinc deficiency is reversed by zinc replenishment
and replenished animals have a markedly lower incidence of esophageal
tumors.
相似文献
108.
Relationship of vaginal pH and Papanicolaou smear results to vaginal flora and pregnancy outcome 总被引:2,自引:0,他引:2
H Minkoff A Grunebaum J Feldman M Cummings W M McCormack 《International journal of gynaecology and obstetrics》1987,25(1):17-23
Prematurity is a major cause of perinatal morbidity. Studies have implicated components of the vaginal flora in the etiology of some cases of preterm birth. Current scoring systems do not include factors which directly reflect the vaginal flora. Since Papanicolaou smears and the vaginal pH may be affected by the vaginal flora and are easy tests to perform, we studied their relationship to vaginal flora and pregnancy outcome. Among 231 patients, those with a vaginal pH greater than or equal to 4.4 were significantly more likely to carry Trichomonas vaginalis (P less than 0.03); Bacteroides species (P less than 0.01), and Mycoplasma hominis (P less than 0.001), and to have premature rupture of the membranes (P less than 0.01), and preterm rupture of the membranes (P less than 0.05). Patients with atypia reported on Papanicolaou smear more frequently carried M. hominis (P less than 0.01), and had premature rupture of the membranes (P less than 0.01). Although the high sensitivity and negative predictive value of those tests may make them useful additions to current scoring systems, their low specificity prevents them from being independent predictors of risk. 相似文献
109.
Kimberly A Bertrand Rulla M Tamimi Christopher G Scott Matthew R Jensen V Shane Pankratz Daniel Visscher Aaron Norman Fergus Couch John Shepherd Bo Fan Yunn-Yi Chen Lin Ma Andrew H Beck Steven R Cummings Karla Kerlikowske Celine M Vachon 《Breast cancer research : BCR》2013,15(6):R104
Introduction
Understanding whether mammographic density (MD) is associated with all breast tumor subtypes and whether the strength of association varies by age is important for utilizing MD in risk models.Methods
Data were pooled from six studies including 3414 women with breast cancer and 7199 without who underwent screening mammography. Percent MD was assessed from digitized film-screen mammograms using a computer-assisted threshold technique. We used polytomous logistic regression to calculate breast cancer odds according to tumor type, histopathological characteristics, and receptor (estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER2)) status by age (<55, 55–64, and ≥65 years).Results
MD was positively associated with risk of invasive tumors across all ages, with a two-fold increased risk for high (>51%) versus average density (11-25%). Women ages <55 years with high MD had stronger increased risk of ductal carcinoma in situ (DCIS) compared to women ages 55–64 and ≥65 years (Page-interaction = 0.02). Among all ages, MD had a stronger association with large (>2.1 cm) versus small tumors and positive versus negative lymph node status (P’s < 0.01). For women ages <55 years, there was a stronger association of MD with ER-negative breast cancer than ER-positive tumors compared to women ages 55–64 and ≥65 years (Page-interaction = 0.04). MD was positively associated with both HER2-negative and HER2-positive tumors within each age group.Conclusion
MD is strongly associated with all breast cancer subtypes, but particularly tumors of large size and positive lymph nodes across all ages, and ER-negative status among women ages <55 years, suggesting high MD may play an important role in tumor aggressiveness, especially in younger women. 相似文献110.
Effect of Alendronate on Risk of Fracture in Women With Low Bone Density but Without Vertebral Fractures: Results From the Fracture Intervention Trial 总被引:40,自引:7,他引:40
Cummings Steven R.; Black Dennis M.; Thompson Desmond E.; Applegate William B.; Barrett-Connor Elizabeth; Musliner Thomas A.; Palermo Lisa; Prineas Ronald; Rubin Susan M.; Scott Jean C.; Vogt Thomas; Wallace Robert; Yates A. John; LaCroix Andrea Z.; for the Fracture Intervention Trial Research Group 《JAMA》1998,280(24):2077-2082
Context. Alendronate sodium reduces fracture risk in postmenopausal women who have vertebral fractures, but its effects on fracture risk have not been studied for women without vertebral fractures. Objective. To test the hypothesis that 4 years of alendronate would decrease the risk of clinical and vertebral fractures in women who have low bone mineral density (BMD) but no vertebral fractures. Design. Randomized, blinded, placebo-controlled trial. Setting. Eleven community-based clinical research centers. Subjects. Women aged 54 to 81 years with a femoral neck BMD of 0.68 g/cm2 or less (Hologic Inc, Waltham, Mass) but no vertebral fracture; 4432 were randomized to alendronate or placebo and 4272 (96%) completed outcome measurements at the final visit (an average of 4.2 years later). Intervention. All participants reporting calcium intakes of 1000 mg/d or less received a supplement containing 500 mg of calcium and 250 IU of cholecalciferol. Subjects were randomly assigned to either placebo or 5 mg/d of alendronate sodium for 2 years followed by 10 mg/d for the remainder of the trial. Main Outcome Measures. Clinical fractures confirmed by x-ray reports, new vertebral deformities detected by morphometric measurements on radiographs, and BMD measured by dual x-ray absorptiometry. Results. Alendronate increased BMD at all sites studied (P<.001) and reduced clinical fractures from 312 in the placebo group to 272 in the intervention group, but not significantly so (14% reduction; relative hazard [RH], 0.86; 95% confidence interval [CI], 0.73-1.01). Alendronate reduced clinical fractures by 36% in women with baseline osteoporosis at the femoral neck (>2.5 SDs below the normal young adult mean; RH, 0.64; 95% CI, 0.50-0.82; treatment-control difference, 6.5%; number needed to treat [NNT], 15), but there was no significant reduction among those with higher BMD (RH, 1.08; 95% CI, 0.87-1.35). Alendronate decreased the risk of radiographic vertebral fractures by 44% overall (relative risk, 0.56; 95% CI, 0.39-0.80; treatment-control difference, 1.7%; NNT, 60). Alendronate did not increase the risk of gastrointestinal or other adverse effects. Conclusions. In women with low BMD but without vertebral fractures, 4 years of alendronate safely increased BMD and decreased the risk of first vertebral deformity. Alendronate significantly reduced the risk of clinical fractures among women with osteoporosis but not among women with higher BMD. 相似文献