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Biomedical subjects

K Leitzel

Publications and source records attributed to K Leitzel.

14 recordsLinked to original sources
PubMed2004

Baseline serum NTx levels are prognostic in metastatic breast cancer patients with bone-only metastasis.

BACKGROUND: There is significant heterogeneity in survival of patients with metastatic breast cancer who have bone-only metastasis. We studied the correlation of serum N-telopeptide (NTx), a marker of bone resorption, and its correlation with clinical outcomes in patients with metastatic breast cancer with bone-only or bone plus soft tissue metastasis. PATIENTS AND METHODS: Serum was taken from 250 metastatic breast cancer patients with bone-only or bone plus soft tissue metastasis who participated in two similar randomized studies of second-line hormone therapy. An enzyme-linked immunosorbent assay specific for NTx of type I bone collagen was used to detect serum levels. RESULTS: Sixty patients (24%) had elevated serum NTx levels, using the mean + 2 standard deviations (26 nanomoles Bone Collagen Equivalents per liter) of healthy women as a cut-off. The median duration of clinical benefit was significantly shorter in the group with elevated serum NTx levels compared with the group that had normal serum NTx levels (P=0.0004). Time to progression (TTP) was also significantly shorter in the patients with elevated serum NTx at 139 days compared with 220 days (P=0.0006). Median survival was also significantly shorter in patients with elevated baseline serum NTx levels at 663 days compared with 941 days (P<0.0001). CONCLUSION: In this study, breast cancer patients with bone-only or bone plus soft tissue metastasis and elevated serum NTx levels have a shorter duration of clinical benefit, TTP and overall survival.

Adult↗
PubMed2003

Serum HER-2/neu and response to the aromatase inhibitor letrozole versus tamoxifen.

PURPOSE: To determine the effect of elevated serum HER-2/neu on the response of metastatic breast cancer patients to an aromatase inhibitor versus an antiestrogen. PATIENTS AND METHODS: Five hundred sixty-two estrogen receptor-positive metastatic breast cancer patients were randomized to first-line hormone therapy with either letrozole or tamoxifen. An automated enzyme-linked immunosorbent assay was used to detect serum HER-2/neu. RESULTS: For patients with normal serum HER-2/neu (70.5%), objective response rate (ORR; 39% in letrozole-treated patients v 26% in tamoxifen-treated patients; P =.008), clinical benefit (CB; 57% v 45%; P =.016), time to progression (TTP; median, 12.2 v 8.5 months; P =.0019), and time to treatment failure (TTF; median, 11.6 v 6.2 months; P =.0066) were significantly better in patients treated with letrozole. In the elevated HER-2/neu group (29.5%), there was no significant difference in ORR (17% in letrozole-treated patients v 13% in tamoxifen-treated patients; P =.45) or CB (33% v 26%; P =.31), but there was a strong trend in favor of a longer TTP with letrozole (median, 6.1 v 3.3 months; P =.0596) and a significantly longer TTF with letrozole (median, 6.0 v 3.2 months; P =.0418). Multivariate analysis revealed that elevated serum HER-2/neu was a negative predictor for ORR and TTP. CONCLUSION: Patients with normal serum HER-2/neu receiving letrozole demonstrated a significantly greater ORR and CB and longer TTP and TTF than patients receiving tamoxifen. Although in patients with elevated serum HER-2/neu there was no significant difference between letrozole and tamoxifen in ORR or CB, there was a strong trend favoring longer TTP and significantly longer TTF with letrozole.

Adult↗
PubMed2002

Elevated serum Her-2/neu level predicts decreased response to hormone therapy in metastatic breast cancer.

PURPOSE: To determine the effect of elevation of serum HER-2/neu on response to hormone therapy. PATIENTS AND METHODS: Seven hundred nineteen metastatic patients with estrogen receptor-positive (ER(+)), progesterone receptor-positive, or both or ER status unknown breast cancer were randomized in three independent clinical trials to receive second-line hormone therapy with either megestrol acetate or an aromatase inhibitor (fadrozole or letrozole). An automated enzyme-linked immunosorbent assay specific for the extracellular domain of the HER-2/neu (c-erbB-2) oncoprotein product was used to detect serum levels. RESULTS: Two hundred nineteen patients (30%) had elevated serum HER-2/neu protein levels, using the mean + 2 SD (15 ng/mL) from the serum of healthy women as an upper limit. Response to treatment was available for 711 patients. The response rate (complete responses plus partial responses plus stable disease) to endocrine therapy was 45% in 494 patients with non-elevated and 23% in 217 patients with elevated serum HER-2/neu levels (P <.0001). Median duration of treatment response (using the time to progression [TTP] variable for patients who responded) was shorter in the group with elevated serum HER-2/neu levels (11.7 months) compared with the patient group with non-elevated levels (17.4 months). TTP, time to treatment failure, and median survival (17.2 months v 29.6 months) were also significantly shorter in the patients with elevated serum HER-2/neu levels (P <.0001). CONCLUSION: Patients with ER(+) and serum HER-2/neu-positive metastatic breast cancer are less likely to respond to hormone treatment and have a shorter duration of response than ER(+) and serum HER-2/neu-negative patients. Their survival duration is also shorter.

Aged↗
PubMed1998

Detection of cancer cells in peripheral blood of breast cancer patients using reverse transcription-polymerase chain reaction for epidermal growth factor receptor.

The epidermal growth factor receptor (EGFR) has been reported to be expressed in high levels in primary breast cancer by immunohistochemistry. In the present study, a reverse transcription (RT)-PCR assay using EGFR primers was developed and evaluated for the detection of circulating micrometastases in the blood of breast cancer patients. Total RNA was extracted from breast cancer cell lines and from the blood of 23 control individuals and 37 breast cancer patients. After reverse transcription, outer and nested primers for EGFR were used for cDNA amplification. RNA integrity was confirmed with parallel RT-PCR amplification using beta2-microglobulin primers. PCR products were electrophoresed on agarose gels containing ethidium bromide and visualized by UV photography. Southern blotting was used to confirm EGFR specificity. The nested EGFR RT-PCR assay was capable of detecting a lower limit of 100 fg of total RNA from the A431 cell line. EGFR RNA was identified from the blood of 4 of 18 (22%) metastatic breast cancer patients, 0 of 6 locally recurrent breast cancer patients, 0 of 13 adjuvant breast cancer patients, and 0 of 23 controls (P = 0.03, metastatic versus control). The 18 metastatic breast cancer patients all had progressive disease at the time of blood sampling. The identity of the four EGFR-positive bands was confirmed by Southern blotting. The presence of RT-PCR positivity for EGFR was not a treatment-related phenomenon, because three of the four EGFR-positive patients were not receiving treatment at the time of blood collection. RT-PCR for EGFR is a sensitive and specific method for the detection of circulating micrometastases in a proportion of patients with metastatic breast cancer.

Biomarkers, Tumor↗
PubMed1996

Serial serum c-erbB-2 levels in patients with breast carcinoma.

BACKGROUND: Recently, the extracellular domain of the c-erbB-2 oncogene product (HER-2/neu) has been reported to be elevated in the serum of one-fourth of patients with metastatic breast carcinoma. The role of serum c-erbB-2 as a tumor marker, however, is still poorly defined. The purpose of this study was to evaluate the utility of serial serum c-erbB-2 levels as a tumor marker in patients with metastatic breast carcinoma. METHODS: c-erbB-2 levels in the sera of patients with breast carcinoma were determined by an enzyme immunoassay that detects the extracellular domain of c-erbB-2. Serum c-erbB-2 levels were evaluated prior to treatment as well as throughout the course of treatment with second-line hormonal therapy employing either megestrol acetate or fadrozole, an experimental aromatase inhibitor. RESULTS: Fifty-eight of 300 patients (19.3%) had elevated pretreatment serum c-erbB-2 levels. Of these 58 patients with elevated pretreatment c-erbB-2, 48 had more than 1 visit which enabled us to quantitate serial c-erbB-2 levels throughout the course of treatment. Of these 48 patients, 28 (58.3%) had serial c-erbB-2 values that correlated with the clinical course. CONCLUSIONS: Serial serum c-erbB-2 levels did not show a high overall correlation with the clinical course in this group of patients with metastatic breast carcinoma treated with second-line hormonal therapy.

Aged↗
PubMed1995

Elevated serum c-erbB-2 antigen levels and decreased response to hormone therapy of breast cancer.

PURPOSE: Decisions concerning the use of hormone therapy to treat metastatic breast cancer are made on the basis of the presence of estrogen receptor (ER). Despite the presence of ER, half of patients will not respond to hormone treatment. The purpose of this study was to determine the effect of overexpression of HER-2/neu on the response to hormone therapy. PATIENTS AND METHODS: Sera from 300 metastatic breast cancer patients with ER-positive (ER+), ER status unknown, or ER-/progesterone receptor-positive (PR+) randomized to receive second-line hormone therapy with either megestrol acetate or fadrozole were evaluated. An enzyme immunoassay (EIA) specific for the extracellular domain of the c-erbB-2 (HER-2/neu) oncogene product was used to detect serum levels. RESULTS: Fifty-eight patients (19.3%) had elevated serum c-erbB-2 protein levels, using a selected cut-point of 30 U/mL. The response rate (complete responses [CRs] plus partial responses [PRs] plus stable disease [S]) to endocrine therapy was 40.9% in 242 patients with low serum c-erbB-2 levels and only 20.7% in 58 patients with elevated serum c-erbB-2 levels (P = .004). The median duration of treatment response was longer in the group with low serum c-erbB-2 levels (15.5 months) compared with the group with elevated serum c-erbB-2 levels (11.6 months). Survival was also significantly shorter in patients with elevated serum c-erbB-2 levels (P < .0001). CONCLUSION: Patients with ER+/c-erbB-2+ metastatic breast cancer are less likely to respond to hormone treatment than ER+/c-erbB-2- patients. Their survival duration is also shorter.

Adult↗
PubMed1992

Elevated soluble c-erbB-2 antigen levels in the serum and effusions of a proportion of breast cancer patients.

PURPOSE: An enzyme-linked immunosorbent assay (ELISA) for the extracellular domain of the c-erbB-2 oncogene product was developed and evaluated to determine if soluble c-erbB-2 could be detected in the serum and effusions of cancer patients. PATIENTS AND METHODS: Sera from 208 previously untreated or progressing cancer patients and 69 healthy controls were assayed in a double-antibody sandwich ELISA that used two monoclonal antibodies to the native extracellular domain of the c-erbB-2 receptor. Fisher's exact test was used to analyze the statistical significance of the frequency of elevated serum c-erbB-2 levels. Immunoprecipitation and Western blotting were used to characterize further the c-erbB-2 immunoreactivity in the serum of four breast cancer patients. RESULTS: Sera from 12 of 53 patients (23%) with metastatic or locally advanced breast cancer, zero of 69 controls, one of 31 patients with ovarian cancer (3%), and two of 124 other cancer patients (2%) had soluble c-erbB-2 values greater than or equal to 5 U/mL. The number of breast cancer patients with elevated serum c-erbB-2 levels was significantly greater than that of the control group (P less than .0001), the ovarian cancer group (P less than .03), and the other cancers group (P less than .0001). Also, two of five effusions (40%) from breast cancer patients had an elevated soluble c-erbB-2 antigen level, compared with zero of 17 effusions from patients with benign diseases. Western blotting of four sera from breast cancer patients with elevated serum c-erbB-2 antigen levels produced bands of approximately 105 kD that seemed to correlate in intensity with increasing ELISA serum levels. CONCLUSION: Serum c-erbB-2 levels are elevated in approximately one fourth of patients with locally advanced or metastatic breast cancer.

Adult↗
PubMed1991

Elevated plasma platelet-derived growth factor B-chain levels in cancer patients.

Platelet-derived growth factor (PDGF) is produced by a variety of normal and tumor cells in vitro. We have developed an enzyme-linked immunosorbent assay for the detection of the B-chain of PDGF. This assay can reliably detect 0.1 ng/ml of homodimeric recombinant PDGF B-chain and does not cross-react with recombinant PDGF-AA, epidermal growth factor, basic fibroblast growth factor, or transforming growth factor-beta. Citrated plasma from 72 control individuals had a PDGF B-chain (PDGF-B) level of 0.32 +/- 0.14 ng/ml (mean +/- SD) with a range of 0.10-0.69 ng/ml. The plasma platelet factor 4 (PF4) level was 97 +/- 70 ng/ml, with a range of 34-363 ng/ml. Citrated plasma was obtained from 131 cancer patients, and plasma PDGF-B was elevated in 19 (15%) of the patients. Both PDGF-B and PF4 were elevated in 14 (11%) of these patients, consistent with a platelet source of PDGF-B. In 5 patients (4%), however, PDGF-B was elevated and PF4 was not elevated compared to the control group. This last group of patients may have a tumor-derived source of PDGF-B which could be important in autocrine or paracrine growth stimulation of the tumor cells.

Adult↗
PubMed1985

Growth factors and wound healing in the hamster.

We have investigated the effect of topically applied mitogenic preparations on the healing of full-thickness skin wounds in the Syrian hamster. In an attempt to accelerate the healing process, dexamethasone and insulin, platelet-derived growth factor, fibroblast growth factor, thrombin, defined medium F for fibroblasts, liver cell supernatant, epidermal growth factor, and colostrum were applied to the wounds. These mitogens had no significant influence on the rate of wound contraction or on the time to complete healing in full-thickness, noncompromised skin wounds in this animal model.

Animals↗
PubMed1983

Interaction of human tumor cells with human platelets and the coagulation system.

This paper reports studies on the interaction between human platelets, the plasma coagulation system, and two human tumor cell lines grown in tissue culture: Melanoma and breast adenocarcinoma. The interaction was monitored through the use of 125I-labelled fibrinogen, which measures both thrombin activity generated by cell-plasma interaction and fibrin/fibrinogen binding to platelets and tumor cells. Each tumor cell line activates both the platelets and the coagulation system simultaneously resulting in the generation of thrombin or thrombin-like activity. The melanoma cells activate the coagulation system through "the extrinsic pathway" with a tissue factor-like effect on factor VII, but the breast tumor seems to activate factor X directly. Both tumor cell lines activate platelets to "make available" a platelet-derived procoagulant material necessary for the conversion of prothrombin to thrombin. The tumor-derived procoagulant activity and the platelet aggregating potential of cells do not seem to be inter-related, and they are not specific to malignant cells.

Adenocarcinoma↗
PubMed1983

Inhibition of wound healing by topical steroids.

A new animal model was used to study the effect of topical agents on wound healing. A weak- (hydrocortisone cream 1%) and medium-strength (fluocinolone acetonide ointment 0.025%) steroid and their vehicles were applied to full-thickness skin wounds placed on the backs of female Syrian hamsters. Wound healing was significantly retarded by both steroids when compared to their vehicles. Fluocinolone had a greater inhibitory effect than hydrocortisone.

Administration, Topical↗