The influence of small field sizes, penumbra, spot size and measurement depth on perturbation factors for microionization chambers.

The purpose of this study was the investigation of perturbation factors for microionization chambers in small field dosimetry and the influence of penumbra for different spot sizes. To this purpose, correlated sampling was implemented in the EGSnrc Monte Carlo (MC) user code cavity: CScavity. CScavity was first benchmarked against results in the literature for an NE2571 chamber. An efficiency increase of 17 was attained for the calculation of a realistic chamber perturbation factor in a water phantom. Calculations have been performed for microionization chambers of type PinPoint 31006 and PinPoint 31016 in full BEAMnrc linac simulations. Investigating the physical backgrounds of the differences for these small field settings, perturbation factors have been split up into (1) central electrode perturbation, (2) wall perturbation, (3) air-to-water perturbation (chamber volume air-to-water) and (4) water volume perturbation (water chamber volume to 1 mm(3) voxel). The influence of different spot sizes, position in penumbra, measuring depth and detector geometry on these perturbation factors has been investigated, in a 0.8 x 0.8 cm(2) field setting. p(cel) for the PP31006 steel electrode shows a variation of up to 1% in the lateral position, but only 0.4% for the PP31016 with an Al electrode. The air-to-water perturbation in the optimal scanning direction for both profiles and depth is most influenced by the radiation field, and only to a small extent the chamber geometry. The PP31016 geometry (shorter, larger radius) requires less total perturbation within the central axis of the field, but results in slightly larger variations off axis in the optimal scanning direction. Smaller spot sizes (0.6 mm FWHM) and sharper penumbras, compared to larger spot sizes (2 mm FWHM), result in larger perturbation starting in the penumbra. The longer geometries of the PP31006/14/15 exhibit in the non-optimal scanning direction large variations in total perturbation (p(tot) 1.201(4) (0.6 mm spot, 3 mm off axis, type A MC uncertainty) to 0.803(4) (5 mm off axis)) mainly due to volume perturbation. Therefore in IMRT settings, when the detector is not always in the optimal scanning direction, the PP31016 geometry requires less extreme perturbation (max p(tot) 1.130(3)) and shows less variation. However, these results suggest that small variations in positioning, spot size or MLC result in large differences in perturbation factors. Therefore even these 0.016 cm(3) ionization chambers are limited in their use for a field setting of 0.8 x 0.8 cm(2), as used in this investigation.

On the calibration process of film dosimetry: OLS inverse regression versus WLS inverse prediction.

The purpose of this study was both putting forward a statistically correct model for film calibration and the optimization of this process. A reliable calibration is needed in order to perform accurate reference dosimetry with radiographic (Gafchromic) film. Sometimes, an ordinary least squares simple linear (in the parameters) regression is applied to the dose-optical-density (OD) curve with the dose as a function of OD (inverse regression) or sometimes OD as a function of dose (inverse prediction). The application of a simple linear regression fit is an invalid method because heteroscedasticity of the data is not taken into account. This could lead to erroneous results originating from the calibration process itself and thus to a lower accuracy. In this work, we compare the ordinary least squares (OLS) inverse regression method with the correct weighted least squares (WLS) inverse prediction method to create calibration curves. We found that the OLS inverse regression method could lead to a prediction bias of up to 7.3 cGy at 300 cGy and total prediction errors of 3% or more for Gafchromic EBT film. Application of the WLS inverse prediction method resulted in a maximum prediction bias of 1.4 cGy and total prediction errors below 2% in a 0-400 cGy range. We developed a Monte-Carlo-based process to optimize calibrations, depending on the needs of the experiment. This type of thorough analysis can lead to a higher accuracy for film dosimetry.

The role of oncoplastic surgery in breast cancer.

The authors discuss the objectives of oncoplastic surgery in breast cancer management. Indications and advantages are summarised. Some surgical techniques are described. The authors report their own experience with oncoplastic surgery (26 patients who had immediate breast reconstruction after tumorectomy, and 126 patients who had lumpectomy alone. Oncoplastic surgery was characterised by a wider excision, with negative margins in all cases. In isolated breast conservative tumorectomy, 20% of the margins were positive, requiring re-excision or radical mastectomy. Oncoplastic surgery is preferred especially in younger patients with smaller breasts, since it is less cosmetically mutulating and allows complete tumor resection with save margins.

Monte Carlo modeling of the ModuLeaf miniature MLC for small field dosimetry and quality assurance of the clinical treatment planning system.

The purpose of this investigation was the verification of both the measured data and quality of the implementation of the add-on ModuLeaf miniature multileaf collimator (ML mMLC) into the clinical treatment planning system for conformal stereotactic radiosurgery treatment. To this end the treatment head with ML mMLC was modeled in the BEAMnrc Monte Carlo (MC) code. The 6 MV photon beams used in the setup were first benchmarked with a set of measurements. A total ML mMLC transmission of 1.13% of the 10 x 10 cm2 open field dose was measured and reproduced with the BEAMnrc/DOSXYZnrc code. Correspondence between calculated and measured output factors (OFs) was within 2%. Correspondence between MC and measured profiles was within 2% dose and 2 mm distance, only for the smallest 0.5 x 0.5 cm2 field the results were within 3% dose. In the next step, the MC model was compared with Gafchromic film measurements and Pinnacle(3) 7.4 f (convolution superposition algorithm) calculated dose distributions, using a gamma evaluation comparison, for a multi-beam patient setup delivered to a Lucytrade mark phantom. The gamma evaluation of the MC versus Gafchromic film resulted in 3.4% of points not fulfilling gamma

99mTc-HYNIC Annexin-V imaging of tumors and its relationship to response to radiotherapy and/or chemotherapy.

AIM: The aim of this study was to report on the relationship between preradiotherapy and prechemotherapy 99mTc-HYNIC Annexin-V tumor uptake values, reflecting ongoing apoptosis, and outcome to radiotherapy and/or chemotherapy. METHODS: Twenty-three cancer patients underwent staging examinations and a 99mTc-HYNIC Annexin-V scintigraphy and subsequent radiotherapy and/or chemotherapy. Tumor-to-background ratios derived from tomographic 99mTc-HYNIC Annexin-V images were related to treatment outcome as assessed by RECIST criteria. RESULTS: Six patients underwent radiotherapy or radiochemotherapy: 4 exhibited response to treatment, 1 had stable, and 1 progressive disease. Corresponding tumor-to-background ratio's were respectively >or=2.3 (in responders), 1.2 in the patient presenting with stable disease and 1 in the patient presenting with progressive disease. Seventeen patients were treated by chemotherapy alone: 8 were progressive, 1 patient presented with stable disease and 8 responded to treatment. In 1/8 progressive patients a tumor-to-background ratio of 1.4 was found, the others showed no uptake. In the patient presenting with stable disease a ratio of 0.1 was found. In the 8 responders, 7 patients had a tumor-to-background ratio >or=1.3 whereas in 1 patient a ratio of 0.3 was found. Tumor-to-background ratios in responders (complete plus partial) (median 2.5, range: 0.3-4.2) were significantly higher when compared to those obtained in non-responders (stable plus progressive disease) (median 1, range: 0.1-1.4) (P<0.001). CONCLUSION: The findings presented suggest that 99mTc-HYNIC Annexin-V pretreatment uptake may be useful to predict response to chemo- and radiotherapy.

Growth stimulatory angiotensin II type-1 receptor is upregulated in breast hyperplasia and in situ carcinoma but not in invasive carcinoma.

Two different receptors which bind angiotensin II specifically have been identified in humans and were designated angiotensin II type-1 receptor (AT1) and angiotensin II type-2 receptor (AT2). They only have 34% sequence homology and act through different signalling pathways. AT1 stimulation has been implicated in hypertrophy and hyperplasia in various tissues. In order to study the involvement of AT1 in tissues from controls (n=10) and patients with hyperplasia (n=33), ductal carcinoma in situ (DCIS) (n=23) and invasive carcinoma of the breast (n=25), we tested biopsies and breast-derived cell lines using immunocytochemistry, in situ hybridisation and cell proliferation techniques. The results show specific overexpression of AT1 receptor on the cytoplasmic membrane of cells of hyperplastic lesions with and without atypia and on DCIS of the breast. Evidence for growth stimulation is provided by in vitro experiments showing growth induction by angiotensin II of T47D cells which express the AT1 but not the AT2 receptor. The expression of AT1 on the cell membrane disappears in invasive breast cancer cells suggesting a regulatory pathway which is no longer needed in invasive carcinoma. The specific AT1 expression upregulation might well be an important step in the pathogenesis of hyperplasia of the breast, which is regarded as a precursor lesion for breast cancer.

An implementation strategy for IMRT of ethmoid sinus cancer with bilateral sparing of the optic pathways.

PURPOSE: To develop a protocol for the irradiation of ethmoid sinus cancer, with the aim of sparing binocular vision; of developing a strategy of intensity-modulated radiation therapy (IMRT) planning that produces dose distributions that (1) are consistent with the protocol prescriptions and (2) are deliverable by static segmental IMRT techniques within a 15-minute time slot; of fine tuning the implementation strategy to a class solution approach that is sufficiently automated and efficient, allowing routine clinical application; of reporting on the early clinical implementation involving 11 patients between February 1999 and July 2000. patients and methods: Eleven consecutive T1-4N0M0 ethmoid sinus cancer patients were enrolled in the study. For Patients 1-8, a first protocol was implemented, defining a planning target volume prescription dose of 60 to 66 Gy in 30-33 fractions and a maximum dose (Dmax) of 50 Gy to optic pathway structures and spinal cord and limit of 60 Gy to brainstem. For Patients 9-11, an adapted (now considered mature) protocol was implemented, defining a (planning target volume) prescription dose of 70 Gy in 35 fractions and a Dmax to optic pathway structures and brainstem of 60 Gy and to spinal cord of 50 Gy. RESULTS: The class solution-directed strategy developed during this study reduced the protocol translation process from a few days to about 2 hours of planner time. The mature class solution involved the use of 7 beam incidences (20-37 segments), which could be delivered within a 15-minute time slot. Acute side effects were limited and mild. None of the patients developed dry eye syndrome or other visual disturbances. The follow-up period is too short for detection of retinopathy or optic nerve and chiasm toxicity. CONCLUSION: Conventional radiotherapy of ethmoid sinus tumors is associated with serious morbidity, including blindness. We hypothesize that IMRT has the potential to save binocular vision. The dose to the optic pathway structures can be reduced selectively by IMRT. Further enrollment of patients and longer follow-up will show whether the level of reduction tested by the clinical protocol is sufficient to save binocular vision. An adaptive strategy of IMRT planning was too inefficient for routine clinical practice. A class solution-directed strategy improved efficiency by eliminating human trial and error during the IMRT planning process.

Autoradiographic evidence for the sliding of the upper layer over the basement membrane in chicken blastoderms during gastrulation.

An upper layer (epiblast) fragment taken laterally from the Anlage fields of neural plate or chordamesoderm of a quail blastoderm, labelled with 3H-glucosamine, was grafted isotopically (in a similar region), isochronically (at the similar stage of development) and isotropically (with the same caudocranial and dorsoventral polarity) in the epiblast of a mesoblast free area of a chicken blastoderm (St 4-5 Vakaet, 1970: full grown primitive streak). On the autoradiographs of the sections through such cultured blastoderms with fully integrated quail grafts, we observed a labelling of the basement membrane laterally and slightly cranially from the labelled graft in its final position. Since only the epiblast and its basement membrane are involved, the pattern of the observed labelling indicates that the grafted and integrated quail epiblast fragment glides in toto over the mediocaudally localized basement membrane, leaving behind a track of radioactivity. Sliding of whole groups of epiblast cells over the basement membrane seems thus to be a normal phenomenon during avian gastrulation.

Radiotherapy of prostate cancer with or without intensity modulated beams: a planning comparison.

PURPOSE: To evaluate whether intensity modulated radiotherapy (IMRT) by static segmented beams allows the dose to the main portion of the prostate target to escalate while keeping the maximal dose at the anterior rectal wall at 72 Gy. The value of such IMRT plans was analyzed by comparison with non-IMRT plans using the same beam incidences. METHODS AND MATERIALS: We performed a planning study on the CT data of 32 consecutive patients with localized adenocarcinoma of the prostate. Three fields in the transverse plane with gantry angles of 0 degrees, 116 degrees, and 244 degrees were isocentered at the center of gravity of the target volume (prostate and seminal vesicles). The geometry of the beams was determined by beam's eye view autocontouring of the target volume with a margin of 1.5 cm. In study 1, the beam weights were determined by a human planner (3D-man) or by computer optimization using a biological objective function with (3D-optim-lim) or without (3D-optim-unlim) a physical term to limit target dose inhomogeneity. In study 2, the 3 beam incidences mentioned above were used and in-field uniform segments were added to allow IMRT. Plans with (IMRT-lim) or without (IMRT-unlim) constraints on target dose inhomogeneity were compared. In the IMRT-lim plan, target dose inhomogeneity was constrained between 15% and 20%. After optimization, plans in both studies were normalized to a maximal rectal dose of 72 Gy. Biological (tumor control probability [TCP], normal tissue complication probability [NTCP]) and physical indices for tumor control and normal tissue complication probabilities were computed, as well as the probability of the uncomplicated local control (P+). RESULTS: The IMRT-lim plan was superior to all other plans concerning TCP (p < 0.0001). The IMRT-unlim plan had the worst TCP. Within the 3D plans, the 3D-optim-unlim had the best TCP, which was significantly different from the 3D-optim-lim plan (p = 0.0003). For rectal NTCP, both IMRT plans were superior to all other plans (p < 0.0001). The IMRT-unlim plan was significantly better than the IMRT-lim plan (p < 0.0001). Again, 3D-optim-unlim was superior to the other 3D plans (p < 0. 0007). Physical endpoints for target showed the mean minimal target dose to be the lowest in the IMRT-unlim plan, caused by a large target dose inhomogeneity (TDI). Medial target dose, 90th percentile, and maximal target dose were significantly higher in both IMRT plans. Physical endpoints for the rectum showed the IMRT-unlim plan to be superior compared to all other plans. There was a strong correlation between the 65th percentile (Rp65) and rectal NTCP (correlation coefficient > or =89%). For bladder, maximal bladder dose was significantly higher in the IMRT-unlim plan compared to all other plans (p < or = 0.0001).P+ was significantly higher in both IMRT-plans than in all other plans. The 3D-optim-unlim plan was significantly better than the two other 3D plans (p < 0.0001). CONCLUSION: IMRT significantly increases the ratio of TCP over NTCP of the rectum in the treatment of prostate cancer. However, constraints for TDI are needed, because a high degree of TDI reduced minimal target dose. IMRT improved uncomplicated local control probability. In our department, IMRT by static segmented beams is planned and delivered in a cost-effective way. IMRT-lim has replaced non-modulated conformal radiotherapy as the standard treatment for prostate cancer.

Collagen vascular diseases and radiation therapy: a critical review.

PURPOSE: Although many oncologists have the impression that patients with collagen vascular disease tolerate radiotherapy less well than other patients, until now this was never described in a review article. METHODS AND RESULTS: The principal objective was to determine whether patients with collagen vascular diseases have a greater risk of severe radiation therapy complications, than those without a collagen vascular disease. However, most of the publications found on this topic are short anecdotal case reports of patients with increased toxicity after radiation. Consequently, the true incidence of these side effects is unknown. CONCLUSIONS: Unless further studies on this subject are reported, each radiation oncologist should be cautious in treating these patients.

Clinical delivery of intensity modulated conformal radiotherapy for relapsed or second-primary head and neck cancer using a multileaf collimator with dynamic control.

BACKGROUND AND PURPOSE: Concave dose distributions generated by intensity modulated radiotherapy (IMRT) were applied to re-irradiate three patients with pharyngeal cancer. PATIENTS, MATERIALS AND METHODS: Conventional radiotherapy for oropharyngeal (patients 1 and 3) or nasopharyngeal (patient 2) cancers was followed by relapsing or new tumors in the nasopharynx (patients 1 and 2) and hypopharynx (patient 3). Six non-opposed coplanar intensity modulated beams were generated by combining non-modulated beamparts with intensities (weights) obtained by minimizing a biophysical objective function. Beamparts were delivered by a dynamic MLC (Elekta Oncology Systems, Crawley, UK) forced in step and shoot mode. RESULTS AND CONCLUSIONS: Median PTV-doses (and ranges) for the three patients were 73 (65-78), 67 (59-72) and 63 (48-68) Gy. Maximum point doses to brain stem and spinal cord were, respectively, 67 Gy (60% of volume below 30 Gy) and 32 Gy (97% below 10 Gy) for patient 1; 60 Gy (69% below 30 Gy) and 34 Gy (92% below 10 Gy) for patient 2 and 21 Gy (96% below 10 Gy) at spinal cord for patient 3. Maximum point doses to the mandible were 69 Gy for patient 1 and 64 Gy for patient 2 with, respectively, 66 and 92% of the volume below 20 Gy. A treatment session, using the dynamic MLC, was finished within a 15-min time slot.

The single-isocentre treatment of head and neck cancer: time gain using MLC and automatic set-up.

PURPOSE: In this manuscript, we studied the difference in the treatment time required to execute a single-isocentre three-field irradiation of the head and neck, using either tray-mounted cerrobend blocks or a multileaf collimator (MLC) for field shaping and automatic set-up. MATERIALS AND METHODS: A total of twenty consecutive, unselected patients (16 males, four females), were eligible for this study because the dose they were to received was 44 Gy (2 Gy/fraction) to the head, neck and supraclavicular regions. Patients were randomly allocated to one of two treatment groups. The first group (n = 11) was treated on a Philips SL-75 linear accelerator (SL-75), using 5 MV photons and tray-mounted cerrobend blocks. The second group (n = 9) was treated on a Philips SL-25 linear accelerator (SL-25-MLC), using 6 MV photons and a MLC. Patients of the second group were treated using the automatic set-up facility of the SL-25-MLC, without entering the treatment room between consecutive fields. RESULTS: Overall treatment time was significantly shorter on the SL-25-MLC than on the SL-75 (P < 0.0001). The difference in total treatment-execution time was in the range of 157 s per treatment session. The largest difference was observed in the set-up time. There was an average of a 125 s time gain per treatment day (P < 0.0001) in favour of the SL-25-MLC. CONCLUSIONS: Compared to tray-mounted cerrobend blocks, a MLC and automatic set-up results in a significant time advantage when a single isocentre technique is used to treat head and neck cancer.

Postoperative radiotherapy of paranasal sinus tumours: a challenge for intensity modulated radiotherapy.

BACKGROUND AND PURPOSE: Intensity modulated radiotherapy (IMRT) is used in our department for treatment of paranasal sinuses. We describe the methodology that was developed together with the clinical implementation, illustrated by a case report. MATERIAL AND METHODS: Patient history, treatment and short follow-up are described. An IMRT, obtained by superposition of static beam segments was implemented. Electronic portal images, compared to digitally reconstructed radiographs (DRR) were used to evaluate and adjust patient positioning. RESULTS, DISCUSSION AND CONCLUSION: IMRT is an appropriate and feasible treatment technique for head and neck cancer in anatomical regions that are difficult to treat. A high tumour dose can be combined with a good sparing of the surrounding organs at risk (OAR's).

Off-line verification of the day-to-day three-dimensional table position variation for radiation treatments of the head and neck region using an immobilization mask.

Variation in the table height position for 175 treatments of 167 patients was calculated as a measure for day-to-day set-up precision in 2063 treatment sessions and resulted in a median standard deviation of 1 mm. The median standard deviations of table longitudinal and lateral position were 3 and 5 mm, respectively.

Execution of a single-isocenter three-field technique, using a multileaf collimator or tray-mounted cerrobend blocks: effect on treatment time.

PURPOSE: In this article, we studied the total treatment time of a single-isocenter three-field irradiation of breast and axilla, using either tray-mounted cerrobend blocks, or a multileaf collimator (MLC) for field shaping. METHODS AND MATERIALS: A total of 20 female, unselected patients were given 50 Gy (2 Gy/fraction) on breast and 46 Gy on axilla and supraclavicular region (2 Gy/fraction). Patients were randomized between two different treatment groups. The first group (n = 10) was treated on a Philips SL-75 linear accelerator (SL-75), using 5 MV photons with tray-mounted cerrobend blocks. The second group (n = 10) was treated on a Philips SL-25 linear accelerator, using 6 MV photons and a MLC (SL-25-MLC). RESULTS: Although the beam-on time on the SL-25-MLC was significantly higher (p < 0.0001) compared to the SL-75, overall treatment time was significantly shorter using a MLC instead of tray-mounted cerrobend blocks (p < 0.0001). The difference in total treatment time was in the range of 100 s per patient per day. The main difference between the two accelerators was observed when setup of the second and third field was done using the automatic setup facility of the SL-25-MLC (avoids entering the treatment room). A mean time gain of 124 s per treatment session was observed using automatic setup. Considering the yearly number of patients receiving this treatment, a total time gain equivalent to 16.15 8-h workdays was calculated. CONCLUSIONS: Compared to a technique using tray-mounted cerrobend blocks in the single-isocenter three-field irradiation of a breast and axilla, a MLC combined with automatic field setup provides a significant time advantage, by reducing the number of manipulations inside the treatment room.

Morphotypic plasticity in vitro and in nude mice of epithelial mouse mammary cells (NMuMG) displaying an epithelioid (e) or a fibroblastic (f) morphotype in culture.

Transition from an epithelioid (e-) to a fibroblastic (f-) morphotype marks invasiveness in clinical and experimental cancer. To understand better the factors influencing such transitions, we have subcloned and manipulated mouse mammary gland (NMuMG) cell cultures and compared the invasive phenotype of multiple subclones in vitro and in vivo. Cell lines with an e-morphotype expressed E-cadherin homogeneously and were not invasive in vitro. Cells with an f-morphotype were E-cadherin-negative and became fully invasive in vitro upon expression of the ras oncogene. Invasive tumors were produced in node mice after subcutaneous injection of e-type or f-type cells. These tumors showed cystic, glandular and undifferentiated structures. Tumors from f-type cells were E-cadherin-negative whereas e-type tumors stained heterogeneously in immunohistochemical preparations. Our observations demonstrate the impact of the micro-ecosystem on the invasive phenotype, with in vivo downregulation of E-cadherin and stimulation of the e- to f-morphotype transition.

Behaviour of dissociated hypoblast cells on the basal lamina and on extracellular fibrils in the gastrulating chicken embryo.

The spreading behaviour of dissociated hypoblast cells on and besides a band of aligned fibrils associated with the basal lamina of the epiblast was investigated by the use of scanning electron microscopy. A horse-shaped band of aligned fibrils, first demonstrated by Wakely and England (1979), is present during the gastrulation stages of chicken embryos on the ventral side of the epiblast at the cranial and lateral borders of the area pellucida. The basal lamina of the area pellucida situated inside the fibrillar band enables the spreading and probably the locomotion of dissociated cells, which appeared as polarized cells. Numerous cells were also found on the fibrillar band, and these cells lacked distinct lamellae and a polarized shape. Extensions of the cells contacted the extracellular fibrils and, at these sites of contact, the pattern of the fibrils was frequently deformed. From these observations and from previous results emerged the concept that spreading and locomotion of dissociated hypoblast cells, as well as single mesoblast cells and healing hypoblast epithelium, are inhibited by the band of extracellular fibrils, which acts as a physical barrier. The cell biological basis of the mechanism by which extracellular fibrils associated with the basal lamina arrest the migration of hypoblast and mesoblast cells, but guide the migration of primordial germ cells, is discussed.

In vivo and in vitro invasiveness of a rat colon-cancer cell line maintaining E-cadherin expression: an enhancing role of tumor-associated myofibroblasts.

In various cell systems, an inverse relationship was found between expression of E-cadherin, a molecule involved in the Ca(2+)-dependent homophylic cell-to-cell attachment of epithelial cells, and the capacity to invade extracellular matrix gels or normal tissues in vitro. DHD/K12/TRb (PROb) cells, maintained as a cell line derived from a rat colon carcinoma, homogeneously expressed in vitro immunoreactive E-cadherin, which was functional as shown in cell dissociation-reassociation assays. PROb cells were found to be non-invasive in 3 different assays in vitro. However, tumors resulting from a s.c. injection of PROb cells into syngeneic BD-IX rats were invasive, although PROb cells maintained E-cadherin expression in the tumors. Cells from a freshly dissociated PROb tumor showed, not only PROb cells but also tumor-associated myofibroblasts and were able to cross a Matrigel-coated filter. PROb tumors were indeed infiltrated by numerous myofibroblasts, mainly located at the invasive edge of the tumor. Cells from an established culture of tumor-infiltrating myofibroblasts were able to confer upon PROb cells invasiveness through Matrigel-coated filter or into chick-heart fragments. PROb cells maintained their capacity to express E-cadherin after myofibroblast-enhanced Matrigel invasion. Tumor-associated myofibroblasts, but not PROb cells, secreted a 72-kDa collagenase that could play a role in tumor-cell invasion. These results strongly suggest that cells from the tumor stroma, and more specifically myofibroblasts, may be involved in the invasiveness of epithelial tumor cells in vivo, even when E-cadherin expression prevents tumor-cell invasiveness in different in vitro assays.

Mechanism of closure of experimental excision-wounds in the bare upper layer of the chick blastoderm.

The closure of experimental excision-wounds in the upper layer of the gastrulating chick blastoderm was studied by time-lapse videography and videomicrography and by light microscopy, transmission electron microscopy and scanning electron microscopy. One experimental excision-wound was made in the upper layer of stages 4V to 6V blastoderms (Vakaet, Arch. Biol. (Liège) 81:387-426, 1970), in the proamnion where no middle layer cells are present. The deep layer was previously discarded, so that the wounds were made in the bare upper layer. They closed within 2 to 6 hours and further development was normal by in vitro standards. With videography, global movements of the upper layer towards the wound were observed. With videomicrography, the wound submarginal region cells were seen to move like sheep in a flock: individual cells in different directions, the whole flock towards the wound. During closure the shape of the wound edge was irregular. The structure of the epithelium of the wound submarginal region was unchanged throughout closure: a pseudostratified columnar epithelium in which cell divisions occur at its dorsal side and are parallel to its surface. The basal lamina was absent below the edge of the wounds. We propose that the cells of the upper layer are mobile against one another and are not confined to a specific part of the basal lamina. During wound closure the movements of the cells on the basal lamina would be driven by mitotic pressure. This is the horizontal pressure exerted by the addition of daughter cells and their parting during anaphase and telophase.(ABSTRACT TRUNCATED AT 250 WORDS)