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Biomedical subjects

M Tenhunen

Publications and source records attributed to M Tenhunen.

At least 19 recordsLinked to original sources
PubMed2004

Imaging lobular breast carcinoma: comparison of synchrotron radiation DEI-CT technique with clinical CT, mammography and histology.

Different modalities for imaging cancer-bearing breast tissue samples are described and compared. The images include clinical mammograms and computed tomography (CT) images, CT images with partly coherent synchrotron radiation (SR), and CT and radiography images taken with SR using the diffraction enhanced imaging (DEI) method. The images are evaluated by a radiologist and compared with histopathological examination of the samples. Two cases of lobular carcinoma are studied in detail. The indications of cancer are very weak or invisible in the conventional images, but the morphological changes due to invasion of cancer become pronounced in the images taken by the DEI method. The strands penetrating adipose tissue are seen clearly in the DEI-CT images, and the histopathology confirms that some strands contain the so-called 'Indian file' formations of cancer cells. The radiation dose is carefully measured for each of the imaging modalities. The mean glandular dose (MGD) for 50% glandular breast tissue is about 1 mGy in conventional mammography and less than 0.25 mGy in projection DEI, while in the clinical CT imaging the MGD is very high, about 45 mGy. The entrance dose of 95 mGy in DEI-CT imaging gives rise to an MGD of 40 mGy, but the dose may be reduced by an order of magnitude, because the contrast is very large in most images.

Breast Neoplasms↗
PubMed2004

Phase I trial on sms-D70 somatostatin analogue in advanced prostate and renal cell cancer.

Plasma concentrations and tolerability of a novel somatostatin analogue sms-D70 were studied in patients with metastatic hormone-resistant prostate cancer (HRPC) or metastatic renal cell cancer. To overcome the limitations of the octapeptides having affinity only to somatostatin receptor subtypes 2 and 5, HRPC expressing mainly somatostatin receptors 1 and 4, a somatostatin derivative based on the natural somatostatin having affinity to all five somatostatin receptor subtypes, was developed. The in vivo stability of this dextran-conjugated derivative, somatostatin-D70, was confirmed previously in animal studies, and the nanomolar "panaffinity" has been shown in in vitro receptor binding studies on cell lines transfected with the somatostatin receptor genes. Sms-D70 was given with subcutaneous injection once a week at dose levels of 5, 10, 20, 35, and 50 mg. For pharmacokinetic studies, sms-D70 was labeled with 131I. Fourteen patients were treated, of whom 10 had prostate and 4 renal cell cancer. The kinetic data revealed high stability with a long half-life in the blood. The drug was well tolerated, and no grade 4 (WHO) toxicity was observed. The maximal tolerated dose could not be established due to the lack of dose-limiting toxicities. Objective PSA responses were not recorded in these heavily treated patients, but subjective stabilization of pain was observed and urinary symptoms were alleviated in four patients. Three patients with metastatic HRPC received 5-10-mg intravenous injections of sms-D70 once weekly for 4-14 months on a compassionate use basis. In all cases, serum PSA values decreased more than 50% from the pretreatment level, but these results are difficult to interpret due to concomitant treatments given to these patients. In conclusion, sms-D70 was well tolerated in the treatment of metastatic prostate and renal cell cancer, but no responses were found in these heavily treated patients.

Adult↗
PubMed2003

Analysis of depth profiling data obtained by confocal Raman microspectroscopy.

The nominal depth resolution achieved in confocal Raman microscopy is on the order of a few micrometers. Often, however, the depth resolution is decreased by light refraction at the sample surface. The problem can be avoided with the use of an immersion objective and index matching oils. Through this intervention the instrument point-spread function (PSF) can be assumed to be independent of the depth of focus in the sample, and spatially invariant depth profiles can be acquired. In this work the instrument PSF was determined by measuring a depth profile of a thick uniform sample and calculating the first derivative of the depth profile curve. The first-derivative method was also used to determine sample thickness. Convolution with the PSF makes it possible to simulate the behavior of the instrument with different sample functions. It is also possible to use the instrument PSF to deconvolve depth-profiling data. Deconvolution reduces the blurring effect of the instrument and increases the depth resolution. Deconvolution can also be used in analysis of the sample surface position and in layer structure analysis. In this paper we show how the convolution integral can be used with the immersion sampling technique to determine the PSF and how the sample thickness can be determined.

Algorithms↗
PubMed2002

Small-angle x-ray scattering studies of human breast tissue samples.

Small-angle x-ray scattering (SAXS) patterns are recorded from thin breast tissue samples containing healthy and cancerous regions. The SAXS patterns are compared with histo-pathological observations. The information available from SAXS is reviewed, and a model for scattering from collagen is presented. Scattering patterns of collagen at regions far from the tumours are essentially different from those at tumours. The axial period of collagen fibrils is 65.0 +/- 0.1 nm in healthy regions, and 0.3 nm larger in cancer-invaded regions. The average intensity of scattering from cancerous regions is an order of magnitude higher than the intensity from healthy regions. This is interpreted to arise from an increase of the specific surface area of the scatterers, which is due to a disruption of the molecular and supra-molecular structures in cancerous regions and invasion of new types of cells. The differences of the SAXS patterns are large and distinctive enough to suggest that these phenomena may be utilized in mammography.

Breast↗
PubMed2001

Tetracycline derivatives and ceftriaxone, a cephalosporin antibiotic, protect neurons against apoptosis induced by ionizing radiation.

DNA damage induced by low doses of ionizing radiation causes apoptosis, which is partially mediated via the generation of free radicals. Both free radicals and apoptosis are involved in the majority of brain diseases, including stroke, Alzheimer's disease and amyotrophic lateral sclerosis. Because previous studies have shown that tetracycline derivatives doxycycline and minocycline have anti-inflammatory effects and are protective against brain ischemia, we studied whether minocycline and doxycycline or ceftriaxone, a cephalosporin antibiotic with the potential to inhibit excitotoxicity, protect neurons against ionizing radiation in primary cortical cultures. A single dose of 1 Gy significantly increased lactate dehydrogenase release, induced DNA fragmentation in neurons and triggered microglial proliferation. Treatment with minocycline (20 nM), doxycycline (20 nM) and ceftriaxone (1 microM) significantly reduced irradiation-induced lactate dehydrogenase release and DNA fragmentation. The most efficient protection was achieved by minocycline treatment, which also inhibited the irradiation-induced increase in microglial cell number. Our results suggest that some tetracycline derivatives, such as doxycycline and minocycline, and ceftriaxone, a cephalosporin derivative, protect neurons against apoptotic death.

Animals↗
PubMed2000

Subclinical cardiotoxicity following adjuvant dose-escalated FEC, high-dose chemotherapy, or CMF in breast cancer.

We compared adjuvant chemotherapy-related myocardial damage by antimyosin scintigraphy in patients who received either nine cycles of FEC (fluorouracil, epirubicin and cyclophosphamide) where the doses of epirubicin and cyclophosphamide were escalated according to the leucocyte nadir (group I, n = 14), three cycles of FEC followed by high-dose chemotherapy with alkylating agents (CTCb) given with the support of peripheral blood stem cell transplantation (group II, n = 14), or six cycles of standard intravenous CMF (cyclophosphamide, methotrexate and fluorouracil; group III, n = 8). The cardiac uptake of In-111-antimyosin-Fab (R11D10) antibody was measured and the heart-to-lung ratio (HLR) calculated 8-36 months after the last dose of chemotherapy. Cardiac antimyosin antibody uptake was considerably higher among patients treated with nine cycles of dose-escalated FEC than among those who were treated with three cycles of FEC and high-dose CTCb (HLR, median 1.98; range 1.36-2.24 vs median 1.51; range 1.20-1.82; P < 0.001), or those treated with CMF (median 1.44; range 1.15-1.68; P < 0.001). The difference between groups II and III was not significant (P > 0.1). A linear association was found between the cumulative dose of epirubicin and the cardiac antimyosin uptake (P < 0.001). We conclude that subclinical cardiac damage caused by three cycles of conventional-dose FEC followed by one cycle of high-dose CTCb chemotherapy is small as compared with the damage caused by dose-escalated FEC.

Adult↗
PubMed2000

Absorbed dose estimates for 131I-labelled monoclonal antibody therapy in patients with intraperitoneal pseudomyxoma.

Seven patients with intraperitoneal pseudomyxoma originating from the appendix (4 cases) and from the ovary (3 cases) were treated with radioimmunotherapy. During the therapy, nine infusions of 3.0-4.2 GBq of 131I-labelled B72.3 monoclonal antibody were administered. We developed three-dimensional dose calculation software that can utilize activity maps based on SPET images to calculate the absorbed dose distribution using point source kernels. The dose calculation program was employed to calculate absorbed doses to various organs. The calculated dose distributions enable us to evaluate the variation in dose within the organs, which is normally not available using approaches based on geometric models. The patient-specific absorbed dose calculations were compared with doses based on a model that uses photon S-factors derived from a standard phantom. The compared doses agreed well on average, but in some organs showed large discrepancies.

Antibodies, Monoclonal↗
PubMed1999

The use of TL detectors in dosimetry of systemic radiation therapy.

A method for determining absorbed doses to organs in systemic radiation therapy (SRT) is evaluated. The method, based on thermoluminescent (TL) dosimeters placed on the patient's skin, was validated and justified through a phantom study showing that the difference between measured (TL dosimeters in the phantom) and derived (TL method) values is within 10%. Six radioimmunotherapy (RIT) patients with widespread intraperitoneal pseudomyxoma were also studied. In dose evaluations, special emphasis was on kidneys. In addition to the TL method, the absorbed doses to kidneys were calculated using MIRD formalism and a point dose kernel technique. We conclude that in SRT the described TL method can be used to estimate the absorbed doses to those critical organs near the body surface within 50% (1 SD).

Adult↗
PubMed1999

Physical and biological targeting of radiotherapy.

Targeting of radiotherapy can be based on improving physical dose distribution of radiation delivered or on utilization of specific biological processes for targeting. Tools for physical targeting include brachytherapy, hadron therapy, conformal radiotherapy, stereotactic radiotherapy, stereotactically guided conformal fractionated radiotherapy, and intensity-modulated radiotherapy. Biological targeting can be based on specific metabolic pathways such as uptake of iodine-131 by thyroid cancer cells, difference in substrate uptake between cancer cells and normal cells (e.g. boronophenylalanine in boron neutron capture therapy), targeting of radioactive isotopes by specific carrier molecules (radioimmunotherapy, labeled hormone derivatives or bone-seeking phosphonates), or on the distribution of elements in the body (therapy of bone metastases with a calcium analog strontium-89 or phosphorus-32).

Antibodies, Monoclonal↗
PubMed1998

Radiation therapy for breast cancer and clonal chromosome translocations: a fluorescence in situ hybridization study.

The frequency of chromosomal translocations was analyzed in skin fibroblast cell cultures derived from irradiated and nonirradiated skin biopsies from five cases of breast adenocarcinoma in women, who had undergone radiotherapy after surgery. The study was performed at the first annual check-up. Chromosomal in situ suppression (CISS) hybridization was performed using metaphase nonisotopic fluorescence in situ hybridization (FISH) with library probes specific for chromosomes 1, 2, 3, 4, 5, 7, 8, 13, 19, and 20. The results showed that the frequency of clonal translocations in metaphases obtained from irradiated areas was significantly higher than in metaphases from the nonirradiated tissue samples.

Aged↗
PubMed1998

A dielectric method for measuring early and late reactions in irradiated human skin.

BACKGROUND AND PURPOSE: To measure the dielectric constant of irradiated human skin in order to test the feasibility of the dielectric measurements in the quantitation of acute and late radiation reactions. MATERIALS AND METHODS: The dielectric constant of irradiated breast skin was measured at an electromagnetic frequency of 300 MHz in 21 patients during postmastectomy radiotherapy. The measurements were performed with an open-ended coaxial line reflection method. The irradiation technique consisted of an anterior photon field to the lymph nodes and a matched electron field to the chest wall using conventional fractionation of five fractions/week to 50 Gy. Fourteen out of the 21 patients were remeasured 2 years later and the skin was palpated for subcutaneous fibrosis. RESULTS: At 5 weeks the dielectric constant had decreased by 31 and 39% for the investigated skin sites of the photon and electron fields, respectively. There was a statistically significant inverse correlation between the mean dielectric constant and the clinical score of erythema. An unexpected finding was a decrease of the dielectric constant of the contralateral healthy skin during radiotherapy. Two years later a statistically significant positive correlation was found between the dielectric constant at the irradiated skin sites and the clinical score of subcutaneous fibrosis. CONCLUSIONS: Dielectric measurements non-invasively yield quantitative information concerning radiation-induced skin reactions.

Adult↗
PubMed1998

Demonstration of increased collagen synthesis in irradiated human skin in vivo.

Fibrosis is a common side-effect of radiation therapy. As a complex network of cytokines and other mediators plays a central role in the process leading to fibrosis, we used an in vivo method to measure skin collagen synthesis, taking into account the physiological conditions. We determined suction blister (i.e. interstitial) fluid concentrations of types I and III procollagen propeptides, reflecting types I and III collagen synthesis, in irradiated and unirradiated skin of breast cancer patients 1-5 years after surgery and radiation therapy, hence using the patients as their own controls. The mean concentrations of the measured collagen markers were approximately two times higher in the irradiated skin than in the unirradiated contralateral breast skin. The difference slowly diminishes with time. These results indicate that abundant collagen synthesis in the irradiated skin continues several years after discontinuation of the radiation therapy, leading to fibrosis. The method outlined here offers a new in vivo perspective to study events leading to radiation fibrosis.

Aged↗
PubMed1997

The effect of three dimensional activity distribution on the dose planning of radioimmunotherapy for patients with advanced intraperitoneal pseudomyxoma.

BACKGROUND: Six patients with histologically proven peritoneal carcinomatous pseudomyxomas were treated with radioimmunotherapy. METHODS: All the patients received a tracer dose of iodine-131 (131I) labeled B72.3 anti-TAG-72 monoclonal antibody (MoAb) to test the in vivo affinity. After informed consent was obtained the therapeutic dose (>3.7 gigabecquerels [GBq], 100 mCi) of the 131I labeled B72.3 anti-TAG-72 MoAb was infused within 60 minutes intraperitoneally using 2 catheters on both sides of the abdomen. The patients were imaged with single photon emission computed tomography (SPECT) at 3, 10, and 24 days after the therapeutic infusion. Treatment-planning software has been developed in which functional information obtained from SPECT is integrated with anatomic information obtained from computed tomography (CT). The activity distribution from SPECT images is converted to absorbed dose distributions using a point source kernel convolution dose calculation. The absorbed dose calculation requires a radionuclide specific dose kernel. The activity map is divided into equally sized source voxels from which the distribution is calculated for the target voxels that cover the patient volume. The resulting three dimensional (3D) absorbed dose distribution is viewed as isodose contours superimposed on the CT images or as 3D isodose surfaces. RESULTS: The measured activity distribution shows that the cumulated activity and biologic half-life vary in the patient's body. The developed planning system provides a method for calculating patient specific absorbed dose distributions. CONCLUSIONS: The variation of biologic clearance indicates that a 3D dose calculation method incorporating measured activity distributions is needed to quantify absorbed dose distribution.

Humans↗
PubMed1996

Ionizing radiation induces expression of immediate early genes in the rat brain.

In situ hybridization histochemistry and immunocytochemistry were used to examine whether therapeutic ionizing radiation induces expression of immediate early genes in the rat brain. One hour following a single dose of 2 or 15 Gy the expression of c-fos and zif-268 but not of c-jun mRNAs was induced in a scattered cell population in the lateral striatum, whereas in the piriform cortex the expression of zif-268 mRNA was decreased. Other brain regions did not show consistent changes in the mRNA levels. Three hours after radiation the mRNA levels had returned to normal. Immunocytochemistry showed the number of c-Fos and Jun-B-positive neurones to be increased in the striatum and slightly increased in the frontoparietal cortex 1 and 3 h after radiation. The results show that a subpopulation of neurones is sensitive to ionizing radiation at the clinically relevant dose of 2 Gy and that the neuronal response to this irradiation involves altered expression of genes encoding for transcription factors.

Animals↗