Anti-p53 in breast cancer: concordance of different assay procedures and association with p53 antigen expression

OBJECTIVE: Anti-p53 levels detected by different methods were compared in a predefined group of patients with breast cancer and correlated with p53 antigen expression in the corresponding tumors. METHODS: P53 autoantibodies were investigated in 165 patients with primary breast cancer using ELISAs with recombinant or native p53. Immunoblot and indirect immunofluorescence (Huh7) were used for confirmation, p53 antigen expression in the tumor was determined immunohistochemically. RESULTS: Using ELISA, overall 18/165 positives (11%) were detected, with only partly concordant results between the assays. Five positive sera were confirmed by immunoblot, and three also by indirect immunofluorescence. Anti-p53-positive patients detected by more than two assays showed accumulated p53 in the tumor (6/6) and mostly suffered from recurrent tumors (4/6; p = 0.02). In these cases, a trend towards a shortened disease-free interval was found (26 vs. 49 months; n.s.). In patients with a positive or borderline result in only one of the serological methods, there was no increased rate of p53 accumulation compared to anti-p53-negative patients (4/19 versus 35/126). CONCLUSIONS: Lack of assay standardization may partly explain the divergence in reports on anti-p53 and its clinicopathological associations. We speculate that, in different groups of patients, anti-p53 might be induced by different mechanisms.     

Erste Ergebnisse der neoadjuvanten simultanen Radiochemotherapie bei fortgeschrittenen Rektumkarzinomen

Hintergrund: Bei lokal weit fortgeschrittenen Rektumkarzinomen ist das Erreichen eine R0-Resektion schwierig. Muss jedoch makroskopisch oder mikroskopisch Tumorrest zurückgelassen werden, ist die Prognose der Patienten schlecht. In den Leitlinien empfiehlt die Deutsche Krebsgesellschaft deshalb bei Patienten mit T4-Tumoren eine präoperative simultane Radiochemotherapie. Patienten und Methodik: Vom 1.5.1997 bis 30.11.1999 wurde bei 22 Patienten eine neoadjuvante Radiochemotherapie durchgeführt. Appliziert wurde eine Dosis von 45 Gy zuzüglich eines Boostes von 5,4 Gy. In der ersten und fünften Bestrahlungswoche erhielten die Patienten an fünf aufeinander folgenden Tagen eine Dosis von täglich 1000 mg/m² 5-FU als intravenöse Dauerinfusion über 24 Stunden. Bei auftretender Kardiotoxizität wurde die Chemotherapie auf 5-FU-Bolusinfusion oder Ralitrexed umgestellt. Ergebnisse: 19/22 Patienten konnten einer Operation zugeführt werden. Bei 16/19 (84%) der operierten Patienten konnte eine R0-Resektion erreicht werden. Eine funktionserhaltende Behandlung war bei 9/19 (47%) Patienten möglich. Ein Downstaging um mindestens eine T-Kategorie wurde bei 12/19 (63%) Patienten erzielt. Bei einer medianen Nachbeobachtungszeit von 16 Monaten ist bisher kein lokales Rezidiv bei den operierten Patienten aufgetreten. Das progressionsfreie Überleben der operierten Patienten (R0/R1) beträgt nach zwei Jahren 62%, die Überlebensrate 89%, bezogen auf alle Patienten 76%. Schlussfolgerung: Die präoperative simultane Radiochemotherapie kann zu einer verbesserten Rate an R0-Resektionen und sphinktererhaltenden Eingriffen betragen. Purpose: In locally advanced rectal cancer tumor-negative margins often cannot be obtained by surgery alone. Nevertheless only patients with complete tumor resection can be cured. Due to the poor prognosis of patients with R1/R2 resection the "Deutsche Krebsgesellschaft" recommends concurrent preoperative radiochemotherapy for patients with locally advanced rectal cancer. Patients and Methods: Between May 1997 and November 1999 22 patients were treated with preoperative radiochemotherapy. A total dose of 45 Gy with a small-volume boost of 5.4 Gy was delivered in conventional fractionation (single dose 1,8 Gy). On days 1 to 5 and 29 to 33 patients received concurrently 5-fluorouracil (5-FU) as continuous infusion of 1,000 mg/m². If there was any sign of cardiac toxicity chemotherapy was changed to 5-FU/folinic acid or ralitrexed. Results: Surgery following radiochemotherapy was performed in 19/22 patients. Resections with negative margins were achieved in 16/19 (84%) patients. Sphincter-conserving surgery was possible in 9/19 (47%) patients. A downstaging of at least 1 T category was found in 12/19 (63%) patients. With a median follow-up of 16 months no locoregional recurrences occurred in patients who underwent surgery. Two-year disease-free survival of resected patients is 62%, 2-year overall survival is 89%, of the whole population 76%. Conclusion: Preoperative radiochemotherapy followed by surgery is able to achieve clear resection margins in more than 70% of patients with locally advanced rectal cancer and may improve the rate of sphincter-conserving surgery.     

Characterization of binding sites for a GnRH-agonist (buserelin) in human breast cancer biopsies and their distribution in relation to tumor parameters

Summary Gonadotropin-releasing hormone analogs (GnRH-A) have been added to the armentarium in the therapy of hormone-dependent breast cancer in premenopausal women. The effect of chronic GnRH-A-treatment in premenopausal women is based on the suppression of the hypothalamus-pituitary-ovarian axis and the reduction of sex-steroid serum levels. In addition, a number of experimental and clinical data have been accumulated indicating a direct action of GnRH-A on breast cancer cells and tissue. In this study we analyzed 235 human breast cancer biopsies for specific GnRH-A-binding. We demonstrate high affinity GnRH-A binding sites in human breast cancer tissues. The evaluation of clinical data showed no correlation of the level of GnRH-A-binding with classical tumor parameters.     

Changes in bone in a model of spinal cord injury

Bone calcium, histomorphometry, and mechanical strength were evaluated in a model of spinal cord injury. Cortical bone area and rates of formation and apposition at the tibiofibular junction (TFJ) and midshaft of the humerus were measured at 35–42, 42–77, and 77–94 days after transection of the spinal cord. All comparisons were between the animals with a spinal lesion and control animals. A 0.34% difference in the length of the tibia of the two groups of animals was observed, the dry weight of the tibia was 28.4% less in rats with a lesion, and there was no significant difference in the amount of calcium per milligram of bone. At 35 days after surgery, the cortical area in the midshaft of the humerus was slightly less (11%) in rats with a lesion, but by 94 days there was no difference in cortical or medullary area. The final (day 94) cortical area at the TFJ in rats with a lesion was less than that in the controls. Bone formation at the TFJ was similar in both groups in the period of 35–42 days and was similar at 77–94 days in the animals with a lesion, and rates of formation and apposition were greater in the humerus of rats with a lesion; the rates did not differ significantly between groups at either site. At 94 days, trabecular bone area in the tibial metaphysis was 41% less in rats with a lesion. Mechanical parameters were significantly less in the femora, but not the humeri, of rats with a lesion.     

Confusion of identification of o,p′-Kelthane as heptachlor in orange rind extractives

Conclusions Both the glc and the tlc data prove that the unknown compound in the rind of Kelthane-treated oranges was not heptachlor. While the characterization is not absolutely conclusive, there can be no reasonable doubt that it iso,p′-Kelthane, known to be present in technical grade Kelthane. Other workers, using glc, reportedp,p′- ando,p′-Kelthane in the ratio of 100∶1 in 21 market fruit samples from different areas of Southern California. By analogy with DDT, if technical grade Kelthane is assumed to contain up to 20% of theo,p′-isomer this ratio found on fruits treated months previously means that on and in oranges theo,p′-isomer has much the longer half-life (RL₅₀) of the two isomers. On the other hand, approximately equal half-lives are indicated for the two isomers in soil. This brief study emphasizes the need for checking on gas chromatographic data by a more specific method and clearly demonstrates again that improper interpretation of data may be avoided by using at least two columns possessing different retention characteristics for the compounds of interest.