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F Lohr

Publications and source records attributed to F Lohr.

43 records · Page 3Linked to original sources
PubMed1994

Flow cytometric measurement of proliferating cell nuclear antigen (PCNA) in solid tumors.

PURPOSE: The importance of cell kinetic parameters for prognosis and therapeutic strategy is widely accepted in oncology. Repopulation is a major problem in radiotherapy of head and neck tumors. Various assays exist for measuring the proliferation characteristics of individual tumors. However, the existing methods have several drawbacks. MATERIALS AND METHODS: PCNA (proliferating cell nuclear antigen) is expressed in a cell cycle dependent manner. There is a DNA-bound, S-phase specific fraction and a nucleoplasmatic, extractable fraction, which is detectable in all phases except G0. We describe a method for simultaneous measurement of PCNA and DNA in solid tumors using flow cytometry. The assay was applied to three different sublines (AT1, HI, H) of the Dunning rat prostate tumor R3327 and biopsies of twelve human head and neck squamous cell carcinomas. The PCNA-assay was compared to the standard BrdUrd-assay (bromodeoxyuridine) by simultaneous measurement of PCNA and BrdUrd in the animal tumors. RESULTS: Percentages of PCNA-positive cells of 29 +/- 4% (AT1), 25 +/- 7% (HI) and 3 +/- 1% (H) were calculated for the animal tumors with good rank correlation with the BrdUrd-LI. The PCNA-indices for human tumors ranged from 5 +/- 1% up to 70 +/- 9%. CONCLUSION: The flow cytometric PCNA-assay can be applied to standard biopsy material and yields reproducible results with an intratumor variation of about 5% which is small compared to the wide range of PCNA-indices in our series. The method may enhance the pretherapeutic assessment of tumor proliferation kinetics.

Animals↗
PubMed1993

[The relative biological effectiveness (RBE) of fast neutrons on the Dunning rat prostate carcinoma R3327-HI].

Human prostate tumors are known to be good candidates for neutron therapy. The Dunning rat prostate tumor system R3327 was found in many studies to be an excellent model for human prostate tumors. There is still a paucity of studies on the response of the Dunning tumors to fast neutrons. Tumors of the R3327-HI subline are moderately well differentiated and mucin producing. They show one euploid cell population, a bromodeoxyuridine labelling index of 5%, a potential doubling time of 8.9 days, a volume doubling time of about ten days and a cell loss rate of 10%. Tumors were transplanted s.c. in the distal thigh of Copenhagen rats and treated with 60Co-photons (10, 20, 30, 40 Gy, 45 cGy/min) and 14-MeV-neutrons (8, 10, 12 Gy, 7 to 11 cGy/min). Tumor volumes were measured twice weekly. Growth delay was defined as time in days until the tumors reached twice their treatment volume. Linear regressions on the median growth delays of the different treatment groups were calculated. The ratio of the neutron- and photon-slopes yielded an RBE of 3.1 +/- 0.3. Additionally isoeffect-RBE values between 2.3 and 2.6 were graphically estimated.

Animals↗
PubMed1993

Measurement of the proliferative activity of three different sublines of the Dunning rat prostate tumor R3327.

The development of the BrdUrd assay has greatly facilitated the measurement of proliferation in both human and experimental tumors. The potential doubling time (Tpot) was reported to be the most promising parameter to serve as a predictive assay to select patients for new treatment modalities such as accelerated fractionation and fast neutrons. We compared flow cytometry and immunochemistry applied to three sublines of the Dunning rat prostate tumor with differing differentiation. The anaplastic R3327-AT subline has a labeling index (LI) of 7 +/- 0.5% and 8.8 +/- 3.7 measured with flow cytometry and histology respectively, S-phase duration (Ts) of 8 h, a Tpot of 4.7 days and a cell loss factors (phi) of 15%. Proliferating cells are homogeneously distributed. The moderately well differentiated R3327-HI subline shows a LI of 5% (flow cytometry 5 +/- 0.5%, immunohistochemistry 5 +/- 2%), Ts of 10.7 h, Tpot of 8.9 days and phi of 10%. The well differentiated subline R3327-H has two cell populations (DNA-index 1.6) and a labeling index of 3.7 +/- 0.5% measured with flow cytometry and 2.2 +/- 0.4% with immunochemistry.

Animals↗
PubMed1992

Response of the rat Dunning R3327-AT1 prostate tumor to treatment with fractionated fast neutrons.

Reports indicate that cancer of the prostate, soft tissue sarcomas, salivary gland tumors, and melanomas respond well to fast-neutron treatment. To better understand the action of fast neutrons on such tumor tissues, we have begun studies with the versatile Dunning rat prostate tumor system. In our initial studies with the R3327-AT1 subline we observed a relative biological effectiveness (RBE) of approximately 3 for single doses of 14-meV fast neutrons. As a continuation of those studies the present report discusses our findings following fractionated treatments with 10 equal fractions of 14-MeV fast neutrons or 60Co gamma rays at several dose levels per fraction. After either fractionated neutron or photon treatment the volume of the tumors continued to increase for 2 weeks and then reached a plateau, the level of which was dose dependent. Tumor growth resumed and no local control was observed. Analysis of the data using growth delay as biological end point yielded an RBE of approximately 4.2 +/- 1.3.

Animals↗
PubMedDate not supplied

Adjuvant treatment of brain metastases.

With an incidence of 15/10(5) in the general population, brain metastases constitute a serious, debilitating complication in cancer patients. The majority of those patients suffer from more than one metastasis, but up to 30% to 40% present with a solitary lesion. Whole-brain radiotherapy (WBRT) extends median survival from 1 to 2 months for treatment with steroids only, to 4 to 6 months in most series. However, long-term survival (>1-2 years) is observed in up to 10% of patients with favorable prognostic factors, such as solitary lesions, good Karnofsky performance status, and absence of extracranial disease. For those patients, individually optimized treatment is worthwhile. For good-prognosis patients with controlled extracranial disease, surgery in combination with postoperative WBRT should be considered, especially when fast relief of symptoms is mandated. For surgically inaccessible solitary lesions below a size threshold of approximately 30 ccm, stereotactic radiosurgery (RS), although never compared to surgery in a randomized fashion, seems to yield comparable results and is the treatment of choice for more than one lesion in appropriately selected patients. Nevertheless, a number of questions concerning the optimal treatment regimens for brain metastases remain. These mainly concern the radiation dose, need for a combination of RS and WBRT, relative timing of different treatment modalities, and maximum number of brain metastases that can reasonably be treated with RS when long-term progression-free survival is the goal. However, RS is definitely an excellent option for salvage and palliation in patients with short life expectancy, as it is simultaneously noninvasive and cost-effective, with short hospitalization times.

Brain Neoplasms↗