Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although many attempts have been made to predict the occurrence of lymph node metastases from papillary thyroid carcinoma, there are currently no reliable means to accurately predict cervical nodal metastasis. In this study, we present a novel prediction system for the lymph node metastasis based on the histological and cyclin D1 staining features. The frequency of lymph node metastases from a series of 210 papillary thyroid carcinomas was analyzed according to the clinicopathological variables, cyclin D1 staining patterns and BRAF(V600E) mutation in tumor tissue. A total of 113 (54%) patients had lymph node metastasis. Cyclin D1 was constantly expressed at the invasive tumor front and revealed well-defined isolated glands of tumor cells in the extra-tumoral region (isolated glands) and laterally spreading tubular growth along the fibrous septa around the invasive front of the tumor (lateral tubular growth). Upon univariate analysis, an age of less than 45 years (P<0.001), tumor size of 10 mm or more (P<0.001), non-follicular variant (P=0.005), invasive growth pattern (P=0.007), extrathyroid extension (P=0.006), isolated glands (P<0.001), lateral tubular growth (P<0.001) and tumor multiplicity (P=0.005) predicted lymph node metastasis, whereas BRAF(V600E) mutation did not. Upon multivariate analysis, age (P=0.001, odds ratio (OR)=5.146), tumor size (P=0.034, OR=3.119), isolated glands (P<0.001, OR=21.042) and lateral tubular growth (P<0.001, OR=24.652) were found to be strong independent predictors of lymph node metastasis. Cyclin D1 staining of papillary thyroid carcinoma is very useful for identifying the intrathyroidal spreading or multifocality of the tumors. Tumor growth patterns verified by cyclin D1 staining can be used for the identification of papillary thyroid carcinomas with metastatic potential.
 ...
PMID:Unique patterns of tumor growth related with the risk of lymph node metastasis in papillary thyroid carcinoma. 2054 22

First line treatment of metastatic melanoma includes the methylating agent dacarbazine or its analogue temozolomide (TMZ) with improved pharmacokinetics and tolerability. However, the prognosis of the metastatic disease is poor and several trials are evaluating TMZ in polychemotherapy protocols. The novel glutathione transferase P1-1 (GSTP1-1) inhibitor 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) has recently shown activity against melanoma through c-Jun N-terminal kinase activation. In this study we have investigated the in vitro and in vivo efficacy of NBDHEX and TMZ combination against melanoma. The results indicated that NBDHEX and TMZ exerted in vitro synergistic anti-proliferative effects in murine B16 and human A375 melanoma cells. In B16 cells TMZ as single agent caused cell accumulation at the G(2)/M phase of cell cycle, whereas NBDHEX induced mainly apoptotic effects. NBDHEX provoked a higher level of p53 phosphorylation with respect to TMZ and the drug combination caused a more than additive increase of p53 activation. The in vivo efficacy of NBDHEX and TMZ has been investigated in an orthotopic B16 model. Treatment with NBDHEX provoked a reduction of tumour growth comparable to that obtained with TMZ, whereas the drug combination significantly increased tumour growth inhibition with respect to the single agents, without worsening TMZ myelotoxicity. Immunohistochemical analysis of tumour grafts revealed a profound reduction of Cyclin D1 and CD31 in all treatment groups; VEGF expression was, instead, markedly decreased only in NBDHEX or NBDHEX and TMZ treated samples. These findings indicate that NBDHEX represents a good candidate for combination therapies including TMZ, offering new perspectives for the treatment of melanoma.
 ...
PMID:The glutathione transferase inhibitor 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) increases temozolomide efficacy against malignant melanoma. 2126 21

Endocrine therapy in patients with breast cancer can be limited by the problem of resistance. Preclinical studies suggest that complete blockade of the estrogen receptor (ER) combined with inhibition of the epidermal growth factor receptor can overcome endocrine resistance. We tested this hypothesis in a phase II neoadjuvant trial of anastrozole and fulvestrant combined with gefitinib in postmenopausal women with newly diagnosed ER-positive breast cancer. After a baseline tumor core biopsy, patients were randomized to receive anastrozole and fulvestrant or anastrozole, fulvestrant, and gefitinib (AFG) for 3 weeks. After a second biopsy at 3 weeks, all patients received AFG for 4 months and surgery was done if the tumor was operable. The primary endpoint was best clinical response by RECIST criteria and secondary endpoints were toxicity and change in biomarkers. The study closed after 15 patients were enrolled because of slow accrual. Median patient age was 67 years and median clinical tumor size was 7 cm. Four patients had metastatic disease present. Three patients withdrew before response was assessed. In the remaining 12 patients, there were two complete clinical responses (17%), three partial responses (25%), five had stable disease (41%), and two (17%) had progressive disease. Most common adverse events were rash in four patients, diarrhea in four, joint symptoms in three, and abnormal liver function tests in three. There were no grade 4 toxicities and all toxicities were reversible. At 3 weeks, cell proliferation as measured by Ki-67 was significantly reduced in the AFG group (P value = 0.01), with a parallel reduction in the expression of the Cyclin D1 (P value = 0.02). RNA microarray data showed a corresponding decrease in the expression of cell cycle genes. These results suggest that AFG was an effective neoadjuvant therapy and consistently reduced proliferation in ER-positive tumors.
 ...
PMID:A phase II neoadjuvant trial of anastrozole, fulvestrant, and gefitinib in patients with newly diagnosed estrogen receptor positive breast cancer. 2179 26

Cyclin D1 (CCND1) belongs to the family of D-type cyclins involved in cell cycle progression, transcriptional regulation, and cell migration. CCND1 was found to be amplified and overexpressed in a variety of cancers, including some vulvar carcinoma cell lines. To determine the relationship of CCND1 copy number changes and CCND1 protein expression with clinicopathologic features and prognosis, 183 vulvar carcinomas were analyzed on a tissue microarray. Amplification was observed in 32 (22.4%) vulvar cancer specimens and was statistically related to the presence of regional lymph node metastases (P < .001). Detectable CCND1 expression was found in 139 (83.2%) of vulvar carcinomas, and 76 (45.5%) exhibited a moderate or strong expression. Increased levels of CCND1 expression were significantly related to higher patient age (P = .013), positive pN category (P = .004), and negative human papillomavirus status (P < .001). Basaloid as well as verrucous, warty-type, and mixed vulvar carcinomas showed lower CCND1 expression levels than keratinizing or nonkeratinizing tumors (P < .001 and P = .032, respectively). Elevated CCND1 expression levels and amplification of the CCND1 gene were closely connected in the present analysis (P < .001). Patient prognosis was independent from CCND1 amplification status and expression level (P = .57 each). In conclusion, CCND1 is amplified and overexpressed in a substantial proportion of vulvar carcinomas and associated with the occurrence of locoregional lymph node metastases, especially in human papillomavirus-negative tumors.
 ...
PMID:Role of cyclin D1 amplification and expression in vulvar carcinomas. 2240 59

Cyclin D1 expression was examined in benign and differentiated malignant thyroid tumors to determine diagnostic utility and correlation with tumor type, size, and nodal status; 29 follicular adenomas (FA), 23 follicular carcinomas (FCA) and 43 papillary thyroid carcinomas (PTC) (22 with and 21 without nodal metastases) were stained. PTCs included 27 classical (PTCC) and 16 follicular variants (PTCFV). A statistically significant association was found between tumor type and cyclin D1 staining, distribution, and intensity. There were fewer cyclin D1-positive FAs than PTCs (52% vs. 88% respectively; P<0.001) and stain distribution was greater in PTC than FA (P=0.032). More PTCs were positive than FCAs (88% vs. 61%, respectively; P=0.013). All significant comparisons remained significant after adjusting for tumor size. FA did not differ from FCA in staining/intensity. There were fewer cyclin D1-positive FAs than PTCC (52% vs. 89%, respectively; P=0.003) and PTCFV (52% vs. 88%, respectively; P=0.023). FCA also differed significantly from PTCC in staining (61% vs. 89%, respectively; P=0.044) and intensity (P=0.024). In terms of cyclin D1 intensity, FA had significantly less intense staining than PTCC (P=0.004). No significant associations were found between PTC nodal status and any cyclin D1 characteristic. In conclusion, cyclin D1 shows heterogeneity in distribution and intensity in benign and malignant thyroid tumors, which disqualifies it as a primary diagnostic marker in these tumors; however, it may be helpful in distinguishing FA from PTC, especially PTCFV. Its expression by thyroid tumors suggests a role in tumor development and may be an early event in thyroid neoplasia.
 ...
PMID:Cyclin D1 expression in benign and differentiated malignant tumors of the thyroid gland: diagnostic and biologic implications. 2255 12

Papillary thyroid microcarcinoma generally carries an excellent prognosis, and fatal cases are becoming increasingly rare. Their pathologic and molecular features, however, remain largely unknown. We describe 3 cases of papillary thyroid microcarcinoma that, despite surgical and radioiodine treatment, recurred, metastasized, and eventually caused the death of the patients. In addition to morphology, immunohistochemical (cyclin D1 and p53) and molecular analyses (BRAF [v-raf Murine sarcoma viral oncogene homolog B1], KRAS [V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog], HRAS [v-Ha-ras Harvey rat sarcoma viral oncogene homolog], NRAS [neuroblastoma RAS viral oncogene homolog], and PIK3CA [phosphoinositide-3-kinase, catalytic, alpha polypeptide]) were performed. Interestingly, all 3 cases presented with massive lymph node metastases that showed morphological evidence of "tumor progression" (tall cell features, poorly differentiated areas, and high-grade cytologic features). Cyclin D1 was consistently immunoreactive in both primary and metastatic site, whereas p53 was negative. BRAF V600E was absent in both sites, and KRAS, HRAS, NRAS, and PIK3CA were consistently wild type. These data suggest that, in cases of metastatic papillary thyroid microcarcinoma, an accurate morphologic analysis of the metastatic deposits could contribute to a more accurate prediction of tumor behavior.
 ...
PMID:Papillary thyroid microcarcinoma with fatal outcome: evidence of tumor progression in lymph node metastases: report of 3 cases, with morphological and molecular analysis. 2396

Human epidermal growth factor 2 (HER2) positivity rates for gastric or gastroesophageal junction (GEJ) adenocarcinoma have been reported at 15-25%. Cyclin D1 (BCL1) is a non-specific proliferative marker. The prognostic significance of HER2 and cyclin D1 is inconclusive, with contradictory data. The aim of this study was to evaluate the incidence of HER2 overexpression in gastric or GEJ patients. The presence of a possible correlation between HER2 status and cyclin D1 staining was assessed; both were evaluated as prognostic markers for survival. The clinical data and histological specimens of 150 consecutive patients diagnosed with gastric or GEJ adenocarcinoma, and treated at our hospital from June 2005 to March 2009, were analyzed. Pathological specimens were immunohistochemically stained for HER2. Immunoreactivity was determined according to the scoring system for gastric carcinoma. Cyclin D1 immunoreactivity was also tested. The results demonstrated that HER2 was positive in 14/150 (9.3%) patients. HER2-positive (HER2(+)) and HER2-negative (HER2(-)) patients did not differ significantly with regard to other clinicopathological parameters. In a multivariate analysis, HER2 positivity was revealed to be a poor prognosis variable (P=0.046; 95% CI, 1.03-3.58). In patients with non-metastatic disease, median survival was 59 months for HER2(-) and 42 months for HER2+ patients, but this difference was not significant. In patients with metastatic disease, median survival was 9.5 months and 2.5 months for HER2(-) and HER2+ patients, respectively (P=0.041). Cyclin D1 was not idemonstrated to be a prognostic factor and was not associated with HER2 overexpression. The rate of positive HER2 status in the current group of unselected patients with gastric and GEJ adenocarcinoma was relatively low compared with that observed in the literature. Nevertheless, HER2 positivity was associated with a poor prognosis.
 ...
PMID:The incidence and prognostic value of HER2 overexpression and cyclin D1 expression in patients with gastric or gastroesophageal junction adenocarcinoma in Israel. 2342 Feb 89

Prognosis for patients with laryngeal squamous cell carcinoma depends on many factors, among which molecular biological markers receive ever increasing attention. The purpose of this study was to determine the prognostic value of the expression of the proteins p53 and bcl-2 and the proliferation markers Ki-67 and cyclin D1 in laryngeal squamous cell carcinoma. Biopsy specimens from 64 patients aged 34 to 77 years (mean age 56+1.2 years) with invasive laryngeal squamous cell carcinoma, who received combination therapy at the Medical Radiology Research Center, Russian Academy of Medical Sciences, were studied. The level of Ki-67 and the expression of cyclin D1, p53, and bcl-2 were compared with clinical and anatomic parameters (T stage, tumor grade, and the presence of regional metastases), using Student's t-test and fourfold table analysis (X2 or Fisher's exact test). Survival rates were analyzed by the Kaplan-Meier method; the significance of differences between survival curves was confirmed by Cox's F-test. The value p0.05 was taken to be significant. Ki-67 is an important prognostic marker for the N status (p=0.03) and recurrence (p=0.04) and a marker for tumor grading (p<0.01). Cyclin D1 expression is associated with low overall and relapse-free survival rates (p=0.05 and 0.03, respectively). The prognostic marker for a recurrence is p53 (p=0.01) that is related to the N status at the trend level (p=0.08). The marker bcl-2 is associated with high overall survival (p=0.01) and N status at the trend level (p=0.08).
 ...
PMID:[Prognostic value of markers for proliferative activity and apoptotic regulation in laryngeal squamous cell carcinoma]. 2380 65

The roles of many genes in the pathophysiology of lung cancer have been investigated in different studies. Cyclin D1 (CCND1) gene plays a significant role in the transition from G1 to S phase of the cell cycle and in the phosphorylation of retinoblastoma tumor suppressor protein. In this study, we aimed to identify the relationship between CCND1 A870G gene polymorphism with lung cancer. CCND1 A870G genotypes were determined in 75 patients with lung cancer and in 65 control subjects. DNA was isolated from blood samples and then CCND1 A870G gene polymorphism was identified using PCR and RFLP assay. The distribution of CCND1 A870G polymorphism did not show any significant differences in all lung cancer patients and controls. There was no correlation between CCND1 A870G polymorphism and histopathological findings. However, the AA + AG genotype was significantly higher in metastatic patients, when compared with non-metastatic patients. Thus, the results show that CCND1 gene polymorphism may be a predictor for detecting patients with poor survival who having metastatic disease.
 ...
PMID:Relationship between cyclin D1 (A870G) gene polymorphism and lung cancer. 2389 88

Although rare, congenital malignant melanoma (CMM) should be considered in the differential diagnosis of congenital skin lesions. We report a case of CMM in a 4-month-old infant presenting with an enlarging scalp mass, initially thought to be a hemangioma. Incisional biopsy of the lesion showed a compound congenital nevus with atypical cells suggestive of a proliferative nodule versus malignancy on histopathology. Subsequent excisional biopsy revealed malignant melanoma, and further workup confirmed extensive disease with distant metastases. Cytogenetic analysis of both the tumor sites showed highly abnormal karyotypes including pseudotetraploidy, telomere associations, and evidence of gene amplification, all consistent with malignancy. Fluorescence in situ hybridization demonstrated amplification of the MYC gene, with no copy number changes in CDKN2A (INK4/ARF), PTEN, or Cyclin D1. Our report details the cytogenetic and molecular studies of CMM, which provide insight into the biologic behavior of the lesions and may confirm diagnosis when histopathology is not determinant.
 ...
PMID:Congenital malignant melanoma: a case report with cytogenetic studies. 2390 18


<< Previous 1 2 3 4 5 6 Next >>