Search PubMed⌕ Search

Biomedical subjects

B Trock

Publications and source records attributed to B Trock.

At least 19 recordsLinked to original sources
PubMed2001

Proteomic patterns of nipple aspirate fluids obtained by SELDI-TOF: potential for new biomarkers to aid in the diagnosis of breast cancer.

Nipple aspirate fluid (NAF) has been used for many years as a potential non-invasive method to identify markers for breast cancer risk or early detection. Because individual markers have not been optimal, we are exploring the use of surface enhanced laser desorption and ionization time of flight (SELDI-TOF) mass spectrometry to identify patterns of proteins that might define a proteomic signature for breast cancer. SELDI-TOF was used to analyze a study set of NAF samples that included 12 women with breast cancer and 15 healthy controls (the latter included three women with an abnormal mammogram but subsequent normal biopsy). In this preliminary report, we present data showing that SELDI analysis of NAF is rapid, reproducible, and capable of identifying protein signatures that appear to differentiate NAF samples from breast cancer patients and healthy controls, including those with an abnormal mammogram who were later proven to be biopsy normal.

Biomarkers, Tumor↗
PubMed2001

Breast cancer: dietary and environmental oestrogens.

Breast cancer is among the most common of the cancers that occur in women living in western societies. It is a much-feared disease and the risks are confusing and often badly reported. Oestrogen levels are a known risk factor. But is it possible to lower the risk? And where are all the oestrogens coming from?

Breast Neoplasms↗
PubMed1999

Predictive value of cathepsin-D for cervical lymph node metastasis in head and neck squamous cell carcinoma.

BACKGROUND: Prognosis of head and neck squamous cell carcinoma (HNSCC) is strongly associated with cervical lymph node metastasis. Cathepsin-D is a lysosomal protease expressed in all cells. Its role in extracellular matrix degradation is postulated to promote tumor invasion and metastasis. Increased cathepsin-D has been demonstrated in cervical lymph node metastasis in HNSCC. METHODS: Formalin fixed tumor biopsy samples from 34 patients with HNSCC of the oral cavity, oropharynx, or hypopharynx were analyzed for the presence of cathepsin-D by immunohistochemistry (1:8000, Calbiochem, Cambridge, MA). Tumors were considered positive if >50% of cells showed strong cytoplasmic staining. RESULTS: All patients had T1 or T2 lesions ranging in size from 1-4 cm and 19 (56%) had cervical metastasis. Eight (24%) were well differentiated and 26 (76%) were moderately or poorly differentiated. Thirteen tumors (38%) had high cathepsin-D expression that was strongly associated with cervical lymph node metastasis (p = 0.008). When adjusted for tumor stage and grade, cathepsin-D positivity was nearly twice as likely to be associated with node metastasis (p = 0.011). CONCLUSIONS: We demonstrated cathepsin-D expression in biopsies from a subset of patients with HNSCC and a strong association between this protease and cervical lymph node metastases. Cathepsin-D is a potential independent predictor of cervical lymph node metastasis in HNSCC and merits additional study.

Biomarkers, Tumor↗
PubMed1999

Prognostic value of p53, glutathione S-transferase pi, and thymidylate synthase for neoadjuvant cisplatin-based chemotherapy in head and neck cancer.

Neoadjuvant cisplatin-based chemotherapy has been widely used in the last decade for organ preservation or unresectable disease in advanced stage head and neck cancer. We examined the expression of a series of tumor markers that have been associated with chemotherapy resistance in pretreatment biopsies from 68 patients who received cisplatin-based neoadjuvant chemotherapy at either of two institutions. Patients received either cisplatin/5-fluorouracil (n = 49) or cisplatin/paclitaxel (n = 19). Expression of p53, glutathione S-transferase pi (GSTpi), thymidylate synthase (TS), c-erbB2, and multidrug resistance-associated protein was examined by immunohistochemistry. Expression of glutathione synthetase mRNA was measured by in situ hybridization. The overall response rate for cisplatin-based neoadjuvant treatment was 79%. The expression of several of the tumor markers was associated with resistance to neoadjuvant treatment, but none reached statistical significance. Overall survival (OS) was strongly correlated with the absence of p53 expression. The OS at 3 years was 81% in the p53-negative group, whereas it was 30% in the p53-positive group for patients treated with neoadjuvant chemotherapy (P < 0.0001). Expression of GST pi and TS was also significantly correlated with decreased OS after neoadjuvant treatment. At 3 years, the OS rate was 82% in the low GSTpi score group, compared to 46% in the high GSTpi score group (P = 0.0018). In the TS-negative group, the 3-year OS rate was 71% compared with 40% in the TS-positive group (P = 0.0071). We conclude that p53, GSTpi, and TS may be clinically important predictors of survival in patients receiving neoadjuvant chemotherapy for head and neck cancer.

Adolescent↗
PubMed1998

Stromal IGF-II messenger RNA in breast cancer: relationship with progesterone receptor expressed by malignant epithelial cells.

In breast cancer, insulin-like growth factor II (IGF-II) is stromal in origin and is considered an important regulator of tumour epithelium growth. The presence of progesterone receptor (PR) is expression of an intact oestrogen regulatory pathway of breast malignant epithelial cells and represents a parameter of cell differentiation in breast cancer. In this study we have examined the relationship between IGF-II mRNA expression and ER, PR content in 75 breast cancer. Formalin-fixed paraffin-embedded tissue sections were used to preserve histological details. IGF-II mRNA was evaluated by in situ hybridisation method and ER, PR by immunohistochemistry. IGF-II mRNA was scored semi-quantitatively: 2.6% breast tumour specimen expressed no IGF-II mRNA, 46.7% had low levels of expression (IGF-II-) and 50.7% had moderate or high IGF-II mRNA content (IGF-II+). IGF-II mRNA was found in the stroma fibroblasts surrounding malignant lesions and no signal was detected in malignant epithelial cells. In contrast, ER and PR were expressed only by neoplastic epithelial cells and no immunoreactivity was found in the stroma: 50/75 (66.6%) breast cancer specimens were positive for ER (ER+) and 35 (46.6%) for PR (PR+). Both, IGF-II mRNA and PR were directly correlated with the stromal proliferation (p < 0.05 and p < 0.001, respectively). No relationship was found between IGF-II RNA and ER. In contrast 24/35 (73.5%) PR breast cancer tissues were IGF-II+ (p < 0.01) and a strong correlation was found between epithelial PR immunostaining and stromal IGF-II mRNA content (p < 0.003). Our data indicate that in breast cancer IGF-II mRNA is generally expressed by stromal cells and ER and PR by epithelial cancer cells, and that IGF-II mRNA expression is strongly related with both percentage and staining intensity of PR+ epithelial cancer cells. These data support the hypothesis that IGF-II produced by the fibroblasts may exert a paracrin effect on malignant epithelium regulating its differentiation.

Breast Neoplasms↗
PubMed1998

Assessing the clinical impact of prognostic factors: when is "statistically significant" clinically useful?

Very few tumor markers have been recommended for routine clinical care of patients with breast cancer. A framework to determine the clinical utility of tumor markers is required. In a previous publication, a "Tumor Marker Utility Grading System" (TMUGS) was proposed. TMUGS included a semi-quantitative grading scale (0-3+) which can be used to assign a score to a given tumor marker for a given outcome. Only those markers that are felt to be sufficiently strong to influence a therapeutic decision that results in improved clinical outcome for the patient are recommended. The studies from which data are used to assign a TMUGS grade can be placed into one of five Levels of Evidence (LOE). An extension of TMUGS ("TMUGS-Plus") is now proposed in which the relative strength of a prognostic or predictive factor can be estimated and expressed in terms of a risk ratio (RR) for prognostic factors or benefit ratio (BR) for predictive factors. Three categories of prognostic factors and three categories of predictive factors are proposed (strong, moderate, and weak). It is recommended that only LOE type I studies (prospective, highly powered studies of the tumor marker, or meta-analysis of LOE II or III datasets), be used to estimate the RR or BR of a given factor. Finally, a matrix, based on assumptions of acceptable absolute benefits relative to risks, is proposed in which any given tumor marker can be assessed for its clinical utility. TMUGS-Plus should aid in the assessment of published data regarding clinical utility of tumor markers. Perhaps more important, clinical investigators can use TMUGS-Plus to design tumor marker studies that will fulfill criteria for clinical utility, resulting in more rapid acceptance of tumor markers for routine clinical use.

Biomarkers, Tumor↗
PubMed1998

Autoantibodies to the nuclear phosphoprotein nucleophosmin in breast cancer patients.

Nucleophosmin (NPM) is an estrogen-regulated nucleolar phosphoprotein; a substrate for phosphorylation by p34cdc2 kinase, protein kinase C, and casein kinase II; and a repressor of the transcriptional regulating activities of the YY1 and IFN regulatory factor-1 transcription factors. We have completed a pilot study to determine whether autoantibodies to NPM are present in breast cancer patients and explored the ability of these autoantibodies to predict recurrence in breast cancer patients. One hundred breast cancer patients were studied: 50 who recurred, and 50 matched for age and length of follow-up but who did not recur. Patients' sera were collected at the times of diagnosis (T1), six months before recurrence (T2), and at recurrence (T3). Recurrent and nonrecurrent patients did not differ in autoantibody levels at the times of diagnosis or recurrence. However, antiNPM autoantibody levels increase significantly between diagnosis and six months before recurrence in recurrent patients, whereas no change occurs over the comparable time period in nonrecurrent patients (repeated measures ANOVA; P = 0.041). At recurrence, the levels return to those seen at diagnosis. The greater the change in levels between T1 and T2, the greater the risk of recurrence within the next 6 months (conditional logistic regression: increase in risk for highest versus lowest tertile of change from T1 to T2; odds ratio, 3.25; 95% confidence interval, 1.04-10.18; P = 0.043). Consistent with the estrogenic/antiestrogenic regulation of the antigen in breast cancer cells, the levels of antiNPM autoantibodies are decreased 6 months before recurrence in patients treated with the antiestrogen tamoxifen (P = 0.012). The association between antiNPM levels and recurrence remained after adjustment for confounding factors. Further study of antiNPM autoantibody levels as a new and simple, intermediate serum biomarker for predicting both the timing of recurrence and monitoring response to endocrine manipulations in breast cancer patients is warranted.

Adult↗
PubMed1996

BRCA1 testing in families with hereditary breast-ovarian cancer. A prospective study of patient decision making and outcomes.

OBJECTIVES: To identify predictors of utilization of breast-ovarian cancer susceptibility (BRCA1 gene) testing and to evaluate outcomes of participation in a testing program. DESIGN: Prospective cohort study with baseline interview assessment of predictor variables (eg, sociodemographic factors, knowledge about hereditary cancer and genetic testing, perceptions of testing benefits, limitations, and risks). BRCA1 test results were offered after an education and counseling session in a research setting. Outcome variables (including depression, functional health status, and prophylactic surgery plans [follow-up only]) were assessed at baseline and 1-month follow-up interviews. PARTICIPANTS: Adult male and female members (n=279) of families with BRCA1-linked hereditary breast-ovarian cancer (HBOC). RESULTS: Of subjects who completed a baseline interview (n=192), 60% requested BRCA1 test results (43% of all study subjects requested results). Requests for results were more frequent for persons with health insurance (odds ration [OR], 3.74; 95% confidence interval [CI], 2.06-6.80); more first-degree relatives affected with breast cancer (OR, 1.59; 95% CI, 1.16-2.16); more knowledge about BRCA1 testing (OR, 1.85; 95% CI, 1.36-2.50); and indicating that test benefits are important (OR, 1.45; 95% CI, 1.13-1.86). At follow-up, noncarriers of BRCA1 mutations showed statistically significant reductions in depressive symptoms and functional impairment compared with carriers and nontested individuals. Individuals identified as mutation carriers did not exhibit increases in depression and functional impairment. Among unaffected women with no prior prophylactic surgery, 17% of carriers (2/12) intended to have mastectomies and 33% (4/12) to have oophorectomies. CONCLUSIONS: Only a subset of HBOC family members are likely to request BRCA1 testing when available. Rates of test use may be higher in persons of a higher socioeconomic status and those with more relatives affected with breast cancer. For some high-risk individuals who receive test results in a research setting that includes counseling, there may be psychological benefits. More research is needed to assess the generalizability of these results and evaluate the long-term consequences of BRCA1 testing.

Adult↗
PubMed1996

Familial uveal melanoma. Clinical observations on 56 patients.

OBJECTIVE: To study the clinical profile and kindreds of patients with familial uveal melanoma (FUM). DESIGN: Retrospective case series. SETTING: Tertiary referral center. PATIENTS: Medical charts of 4500 patients with uveal melanoma were reviewed for family history of uveal melanoma. The clinical profile of these patients and their kindreds were studied to determine the incidence of FUM and pattern of inheritance. The association of FUM to cutaneous melanoma, familial atypical mole and melanoma syndrome, and other nonmelanocytic cancers was analyzed using statistical methods. RESULTS: Of 4500 patients with uveal melanoma, 56 patients in 27 families (0.6%) had a family history of uveal melanoma. The uveal melanoma in all 56 familial patients was unilateral. In 17 cases (63%), the second affected relative was a first-degree relative. In the remainder, the second affected relative was a second- (22%) and third-degree (15%) relative. In 25 families (93%) only two members were affected, and in two families (7%) three members had uveal melanoma. Patients with FUM were four times as likely to have a second primary malignant neoplasm than were people in the general population. However, no evidence was seem that unaffected kindreds of patients with FUM were at higher risk of having a second primary malignant neoplasm. CONCLUSIONS: Familial involvement in uveal melanoma is rare. Familial uveal melanoma most often (63%) affects first-degree relatives, rarely affects more than two persons in a family, and may be associated with a generalized inherited predisposition to cancer. Further genetic studies are necessary to fully characterize FUM syndrome.

Adult↗
PubMed1995

Phase II study of oral etoposide for patients with advanced breast cancer.

BACKGROUND: The objective of this study was to define the activity and toxicity of etoposide for patients with previously treated metastatic breast cancer. METHODS: Thirty patients with measurable metastatic breast cancer who progressed after prior chemotherapy, hormonal therapy, or both, either as adjuvant therapy or for metastatic disease, were enrolled. There were 26 patients evaluable for response and 30 evaluable for toxicity. Treatment consisted of oral etoposide at a dose of 50 mg/m2/day administered for 21 consecutive days. Doses were modified depending on toxicity. Patients were evaluable for response after at least one cycle of therapy. RESULTS: One complete response and four partial responses were observed. The overall objective response rate was 19% (5/26). Six patients had stable disease. Toxicity consisted mainly of Grade 4 neutropenia for 24% and Grade 4 thrombocytopenia for 13% of patients. There was one death due to neutropenic sepsis. CONCLUSION: Oral etoposide is an effective, easily administered outpatient regimen with minimal toxicities. Etoposide is effective for patients with pretreated metastatic breast cancer.

Administration, Oral↗
PubMed1995

Overexpression of the p53 gene in primary and metastatic head and neck carcinomas.

The p53 gene has been correlated with disease progression in a number of human malignancies, and p53 abnormalities are found in a high percentage of head and neck squamous cell carcinomas. The objectives of this study were 1. to correlate p53 expression with disease progression in squamous cell carcinoma of the head and neck (SCCHN), and 2. to determine whether there are site-specific differences in p53 expression. Primary lesions and/or lymph node metastases from 147 patients with invasive SCCHN were immunostained for p53 overexpression. Expression of p53 was similar (42% versus 43%) in primary lesions and lymph node metastases. Expression also did not vary significantly by site in the head and neck. In conclusion, increased p53 expression did not correlate with disease progression in our series of patients with invasive SCCHN. The finding of a lack of increased expression with disease spread to lymph nodes supports the belief that p53 alterations occur early in head and neck carcinogenesis.

Carcinoma, Squamous Cell↗
PubMed1994

p53 is overexpressed in fifty percent of pre-invasive lesions of head and neck epithelium.

To identify the stage in head and neck carcinogenesis at which p53 abnormalities become important, we evaluated 512 squamous epithelial tissue samples (201 pre-invasive and 209 invasive lesions, as well as 102 normal epithelia) in specimens from two institutions. Of 311 patients evaluated, 128 did not have an invasive carcinoma. The frequency of p53 overexpression in the pre-invasive lesions was not influenced by an adjacent invasive tumor. There was an increasing frequency of p53 overexpression in specimens from histologically normal epithelium (5%, with only scattered basal layers positive) to mild (28%) and moderate dysplasia (47%). p53 overexpression was also significantly more common in lesions with severe dysplasia (54%) and carcinoma in situ (CIS; 50%) than in those with mild dysplasia. To further evaluate the timing of p53 alterations in the development of head and neck cancer, paired epithelial samples (one pre-invasive and one invasive) from the same patient were evaluated. A discordance in the p53 staining pattern was seen in approximately one-third of the cases. When a discordance was present, the frequency with which the invasive lesion was positive but the non-invasive negative decreased from 97% (invasive versus normal epithelium) to 50% (invasive versus severe dysplasia or CIS). When p53 expression was evaluated by site, buccal lesions appeared to overexpress p53 more frequently than tongue lesions. In conclusion, p53 protein overexpression is an early event in head and neck carcinogenesis and may represent a biomarker for patients with pre-invasive lesions.

Adult↗
PubMed1994

Effects of topical tretinoin on dysplastic nevi.

PURPOSE: As potential precursors of melanoma and markers of increased melanoma risk, dysplastic nevi are suitable targets of strategies for melanoma chemoprevention. We report the results of a pilot study of topical retinoic acid in patients with dysplastic nevi. PATIENTS AND METHODS: Five male patients with dysplastic nevi applied tretinoin to half of the back for 6 months. Baseline photographs of dysplastic nevi were compared with posttreatment photographs and assessed for morphologic change. At study completion, each subject had four nevi excised from the treated side and four from the untreated side of the back. Biopsies were histologically evaluated for the presence of dysplasia. RESULTS: All patients developed signs of irritation as a result of treatment. One patient was not compliant with treatment due to skin irritation. The four compliant patients showed significant decreases in the clinical atypia of treated lesions, with concomitant fading and even disappearance of many treated nevi. Histologically, only four of 16 treated nevi met histologic criteria for dysplasia, in comparison to 13 of 16 untreated nevi. CONCLUSION: These results suggest that there is concomitant clinical and histologic improvement in a significant percentage of dysplastic nevi treated with topical tretinoin. However, the utility of topical tretinoin for chemoprevention of melanoma is limited by difficulty of application and associated inflammation. While new strategies in chemoprevention of melanoma are explored, sun protection and assiduous avoidance of sunburn must remain the mainstay of melanoma prevention.

Administration, Topical↗
PubMed1993

Natural history of dysplastic nevi.

BACKGROUND: Dysplastic nevi are markers of melanoma risk and potential precursors of melanoma. Few studies have addressed the natural history of dysplastic nevi. OBJECTIVE: Our purpose was to describe the changes observed in nevi over time in a cohort of our patients with dysplastic nevi. METHODS: We used a historical cohort design to study 153 patients with dysplastic nevi observed for a minimum of 5 years. Physical examination at completion of the study was compared with baseline overview and close-up photographs. Lesions excised during the study interval were assessed for history of change. RESULTS: Fifty one percent of all evaluated nevi (297 of 593) showed clinical signs of change during an average follow-up of 89 months. New nevi were common in adulthood and continued to form in more than 20% of patients older than 50 years of age. Nevi were observed to become more clinically atypical, less clinically atypical, and disappear in all age groups. In this small cohort rates of nevus change were not correlated with personal or family history of melanoma, sex, or total number of nevi. Total nevus counts and rates of nevus change were correlated with age. CONCLUSION: Dysplastic nevi remain clinically dynamic in adulthood. Our data suggest that the decrease in counts of dysplastic nevi associated with increasing age is only partly explained by the disappearance of nevi over time and probably reflects a tendency to larger numbers of nevi among more recent birth cohorts.

Adolescent↗
PubMed1993

A cohort study of melanoma in patients with dysplastic nevi.

A historical cohort of 153 patients with dysplastic nevi was studied for the development of melanoma. Each subject had a minimum follow-up of 5 years, with an average study follow-up of 94 months. Eleven new melanomas developed in 11 patients between 11 and 143 months (average 61 months) into the study period. Age-adjusted melanoma incidence in the cohort was 692/100,000 person years. Development of melanoma was strongly correlated with prior personal and/or family history of melanoma. Even among the 89 patients with no personal or family history of melanoma, the age-adjusted incidence of melanoma was an alarming 154/100,000 person years. Within this small, non-randomly ascertained cohort no association could be discerned between melanoma incidence and total number of banal or dysplastic nevi. These findings support the public health significance of the recognition of dysplastic nevi and confirm the importance of family history in evaluating melanoma risk associated with dysplastic nevi.

Adolescent↗