Endovascular treatment of wide-neck anterior communicating artery aneurysms using WEB-DL and WEB-SL: short-term results in a multicenter study.

BACKGROUND AND PURPOSE: Endovascular treatment of wide-neck anterior communicating artery aneurysms can often be challenging. The Woven EndoBridge (WEB) device is a recently developed intrasaccular flow disrupter dedicated to endovascular treatment of intracranial aneurysms. The aim of this study was to investigate the feasibility, safety, and efficacy of the WEB Dual-Layer and WEB Single-Layer devices for the treatment of wide-neck anterior communicating artery aneurysms. MATERIALS AND METHODS: Patients with anterior communicating artery aneurysms treated with the WEB device between June 2013 and March 2014 in 5 French centers were analyzed. Procedural success, technical complications, clinical outcome at 1 month, and immediate and 3- to 6-month angiographic follow-up results were analyzed. RESULTS: Ten patients with unruptured anterior communicating artery aneurysms with a mean neck diameter of 5.4 mm were treated with the WEB. Treatment failed in 3 of the 10 aneurysms without further clinical complications. One patient developed a procedural thromboembolic event, and the other 6 had normal neurologic examination findings at 1-month follow-up. Immediate anatomic outcome evaluation showed adequate occlusion (total occlusion or neck remnant) in 6 of 7 patients. Angiographic control was obtained in all patients, including 6 adequate aneurysm occlusions (3 complete occlusions and 3 neck remnants) at short-term follow-up. CONCLUSIONS: In our small series, treatment of wide-neck anterior communicating artery aneurysms with the WEB device was feasible and safe. However, patient selection based on the aneurysm and initial angiographic findings in the parent artery is important due to the limitations of the WEB device navigation.

Reinterpretation of mouse thyroid changes under space conditions: the contribution of confinement to damage.

During space missions, astronauts work in a state of separation from their daily social environment and in physical confinement. It has been shown that confinement influences mood and brain cortical activity, but no data has been obtained with regard to its effect on the thyroid gland, the structure and function of which change during spaceflights. Here, we report the results of a study on the effects of confinement on mouse thyroid, which was implemented with the Mice Drawer System Facility maintained on the ground, a system used for spaceflight experiments. The results show that confinement changes the microscopic structure of the thyroid gland and that it exhibits symptoms similar to those that result from physiological and/or pathological hyperfunction. What is left unchanged, however, is the sphingomyelinase-thyrotropin receptor relationship, which is important for thyrotropin response with a consequential production of hormones that act on the metabolism of almost all tissues and reduces the production of calcitonin, a hormone involved in bone metabolism. During space missions, the overexpression of pleiotrophin, a widespread cytokine up-regulated after tissue injury that acts on bone remodeling, attenuates changes to the thyroid that are spaceflight-dependent; therefore we studied the thyroids of pleiotrophin-transgenic mice in the Mice Drawer System Facility. In confinement, pleiotrophin overexpression does not protect from the loss of calcitonin. The contribution of confinement to thyroid damage during spaceflights is discussed.

Observing the mouse thyroid sphingomyelin under space conditions: a case study from the MDS mission in comparison with hypergravity conditions.

This is a case report of apparent thyroid structural and functional alteration in a single mouse subjected to low Earth orbit spaceflight for 91 days. Histological examination of the thyroid gland revealed an increase in the average follicle size compared to that of three control animals and three animals exposed to hypergravity (2g) conditions. Immunoblotting analysis detected an increase in two thyroid gland enzymes, sphingomyelinase and sphingomyelin-synthase1. In addition, sphingomyelinase, an enzyme confined to the cell nucleus in the control animals, was found in the mouse exposed to hypogravity to be homogeneously distributed throughout the cell bodies. It represents the first animal observation of the influence of weightlessness on sphingomyelin metabolism.

The thyroid lobes: the different twins.

Although differences in size of the right and left thyroid lobes are well defined, differences in morphology, follicles structure, cAMP production, thyrotropin receptor, and protein involved in cell signalling have not previously been reported. This study provides morpho-functional data of right and left thyroid lobes by biochemical, immunohistochemistry, immunoblotting and immunofluorescence analysis. We demonstrate that, in comparison with the left lobe, the right lobe has a higher activation index, is more sensitive to thyrotropin treatment, is rich in thyrotropin receptor and caveolin 1 involved in thyroid hormone synthesis as well as in epithelial thyroid cell homeostasis, is characterised by a high content of molecules involved in cell signalling such as stat3, raf1, sphingomyelinase and sphingomyelin-synthase whose activity ratio is necessary for epithelial cell activity and finally has more areas calcitonin-dependent. The relation between structure/function of right lobe and its susceptibility to the higher risk of pathological modifications with respect the left lobe is discussed.

Use of an angiographic catheter in place of the Racz epidural catheter in the lysis of epidural space adhesions. A technical note.

This technical note describes lysis of adhesions in the epidural space with the use of a 5F vascular catheter inserted on a 0.35-inch guide passed through the sacral foramen. Commonly employed in the administration of anesthetics, a vascular catheter can be advantageously used in place of the Racz epidural catheter, with a potential reduction in damage to the nerve structures of the sacral canal.

Thyrotropin receptor and membrane interactions in FRTL-5 thyroid cell strain in microgravity.

The aim of this work was to analyze the possible alteration of thyrotropin (TSH) receptors in microgravity, which could explain the absence of thyroid cell proliferation in the space environment. Several forms of the TSH receptor are localized on the plasma membrane associated with caveolae and lipid rafts. The TSH regulates the fluidity of the cell membrane and the presence of its receptors in microdomains that are rich in sphingomyelin and cholesterol. TSH also stimulates cyclic adenosine monophosphate (cAMP) accumulation and cell proliferation. Reported here are the results of an experiment in which the FRTL-5 thyroid cell line was exposed to microgravity during the Texus-44 mission (launched February 7, 2008, from Kiruna, Sweden). When the parabolic flight brought the sounding rocket to an altitude of 264 km, the culture media were injected with or without TSH in the different samples, and weightlessness prevailed on board for 6 minutes and 19 seconds. Control experiments were performed, in parallel, in an onboard 1g centrifuge and on the ground in Kiruna laboratory. Cell morphology and function were analyzed. Results show that in microgravity conditions the cells do not respond to TSH treatment and present an irregular shape with condensed chromatin, a modification of the cell membrane with shedding of the TSH receptor in the culture medium, and an increase of sphingomyelin-synthase and Bax proteins. It is possible that real microgravity induces a rearrangement of specific sections of the cell membrane, which act as platforms for molecular receptors, thus influencing thyroid cell function in astronauts during space missions.

Treatment of a Symptomatic Epidural Gas Cyst Using an Angiographic 5F Catheter in the Epidural Space of the Spinal Cord through the Sacral Hiatus. A Case Report.

An 85-year-old woman arrived at our institution because of left lumbar sciatica of about two years duration unrelieved by conventional oral pain therapy. A computed tomography scan obtained at the second visit showed an epidural gas cyst, with compression and dislocation of the left spinal nerve root L5. The common treatment of an epidural gas cyst is either a direct surgical approach or a CT-guided needle aspiration. We describe an alternative method to mechanical lysis of epidural gas cysts with the use of an 5F angiographic catheter inserted on a 0.035-inch guidewire. This procedure is less invasive than a surgical approach and safer than a CT-guided needle aspiration. Remission of symptoms was maintained at control visits at three and five months.

Rupture of a left internal jugular vein. A rare case.

A 60-year-old woman with neurofibromatosis type 1 presented with a nonpainful swelling in the left laterocervical region that had suddenly arisen after mild exertion the previous evening. Computed tomography with and without contrast enhancement revealed a rupture of the wall of the left internal jugular vein, with a diffuse subcutaneous hematoma. Postoperative histopathologic examination reported diffuse proliferation of plexiform neurofibromatous tissue within the vessel wall.

UVC radiation-induced effect on human primary thyroid cell proliferation and HLA-DR expression.

The aim of this study was to examine how UVC irradiation will affect normal human thyroid cell proliferation and HLA-DR expression. Primary human thyroid cells were exposed to UVC (254 nm wavelength) irradiation. In some experiments 0.5 mM buthionine sulfoximine (BSO) was added. Apoptosis was detected measuring annexin V, proteins involved in apoptotic process (p53, Bax, Bcl-2, caspase 3, and 9) by immunoblot analysis and HLA-DR expression by FACS. UVC induced a cell cycle arrest in G0/G1 phase in the first 24 h, accumulation of cells in the S phase 72 h after treatment, and an increase of apoptotic cells. BSO pretreatment showed an earlier appearance and a higher percentage of apoptosis. p53, caspase 3 and 9 were increased, while Bax and Bcl-2 were decreased. We also observed a transient significant increase in HLA-DR expression. UVC inhibited cell proliferation and induced apoptosis in normal human primary thyroid cells. An inhibitor of glutathione synthesis induced an earlier appearance and higher percentage of apoptosis suggesting that oxidative stress may play a role. Apoptotis involved components of the intrinsic mitochondrial pathway. A transient increase in HLA-DR expression after UVC irradiation could play a role in inducing AITD.

Differential expression of the components of the plasminogen activating system in human thyroid tumour derived cell lines and papillary carcinomas.

We characterised the expression of the plasminogen activators (uPA and tPA), the uPA receptor (uPAR) and the PAs inhibitors (PAI-1 and PAI-2) in human thyroid cell lines derived from normal thyroid, follicular adenoma, follicular, papillary and anaplastic carcinomas. Urokinase PA activity was detected in the supernatant of normal thyrocytes and augmented in those of all tumour cells. Quantitative RT-PCR analysis showed that uPA, uPAR and PAI-1 mRNAs increased in all carcinoma cells. Similar results were found in 13 papillary thyroid carcinoma (PTC) tissues which were mirrored in Western blot experiments. A correlation was found between tumour size and uPA mRNA increase, and higher levels of uPA and uPAR mRNAs were found in metastatic PTC. In conclusion, thyroid carcinoma cell lines and PTC overexpress uPA, uPAR and PAI-1 and the correlation of uPA and its cognate receptor with tumour size and metastasis may suggest their potential prognostic relevance in thyroid cancer.

Qualitative comparison of MR TSE T2 and HASTE in temporomandibular disorders. Clinical observations.

AIM: The aim of the study is to evaluate the quality of the temporal mandibular joint (TMJ) imaging in patients with lack of condyle-disk coordination with the Half-Fourier Acquisition Single Shot Turbo Spin Echo (HASTE), and compare it with the quality of TSE T2-weighted images. METHODS: Twenty-seven patients were selected (12 men and 15 women; age range 17-69 years) with medical history negative for facial trauma or surgery. The instrument used was a Siemens 1.5 Tesla with bilateral coil dedicated for studying both TMJs. TSE T2-weighted and HASTE images in the parasagittal axis with open and closed mouth were obtained for both joints. RESULTS: The quality of the TSE T2-weighted images was better for all parameters considered (both at open and at closed mouth) than the HASTE images; however, the latter method is considerably quicker. CONCLUSIONS: HASTE was found to be a valid method for use as rapid screening to study the TMJ and for use in patients who are unable to maintain an immobile position. Time and cost required for the examination are drastically reduced.

Expression of matrix metalloproteinases and their specific inhibitors in normal and different human thyroid tumor cell lines.

In the present study we investigated, by means of zymography and reverse transcription-polymerase chain reaction (RT-PCR), the expression of different matrix metalloproteinases (MMPs) and of the specific tissue inhibitor of metalloproteinases [TIMPs] in human cell lines derived from normal thyrocytes (HTU5), follicular adenoma (HTU42), and follicular (FTC-133), papillary (B-CPAP), and anaplastic (CAL-62, 8305C) thyroid carcinomas. We demonstrated that normal thyrocytes constitutively express MMP-1, MMP-2, MMP-10, MMP-14, and TIMP-1, TIMP-2, TIMP-3, and TIMP-4, and this pattern of expression is profoundly modified in all thyroid tumor-derived cell lines. Analysis of the gelatinolytic activity in the different cell supernatants showed that the expressions of MMP-2 and MMP-9 are, respectively, increased or induced in all the neoplastic cell lines, except in CAL-62. Caseinolytic activity was found only in the supernatants of the 8305C and B-CPAP cells. Using RTPCR analysis we detected an increased expression of MMP-1 in cell lines derived from papillary and from one (8305C) of the two anaplastic carcinomas. MMP-13 mRNA was expressed only in the 8305C, FTC-133, and BCPAP cells. Among stromelysins, MMP-3 mRNA could not be detected in any cell line, while MMP-10 mRNA was expressed in all of them, although at variable levels. MMP-11 mRNA was absent in normal and follicular adenoma derived thyrocytes and induced in all carcinoma cell types. The expression of MMP-14 (MT1-MMP) mRNA was found significantly increased in all thyroid tumor cell lines with respect to HTU5 and HTU42 cells. The expression of TIMP-1 and TIMP-2 mRNAs was maintained in all cell lines tested, while that of TIMP-3 was lost in both anaplastic carcinoma cell lines and that of TIMP-4 was absent in the CAL-62. In conclusion, our data demonstrated a differential expression of MMPs and TIMPs in different thyroid tumor cell types with respect to normal thyrocytes. In particular, the induction of MMP-11 in all thyroid-derived carcinoma cell lines studied and of MMP-13 in all but one may represent, if confirmed in other thyroid tumor-derived cell lines and in thyroid tumor tissues, a new marker of thyrocyte transformation.

Ten years of preoperative chemoradiation for extraperitoneal T3 rectal cancer: acute toxicity, tumor response, and sphincter preservation in three consecutive studies.

PURPOSE: To compare acute toxicity, tumor response, and sphincter preservation in three schedules of concurrent chemoradiation in resectable transmural and/or node-positive extraperitoneal rectal cancer. PATIENTS AND METHODS: Between 1990 and 1999, 163 consecutive patients were treated according to the following combined modalities: FUMIR: between 1990 and 1995, 83 patients were treated with bolus i.v. mitomycin C (MMC), 10 mg/m(2) day 1, plus 24-h continuous infusion i.v. 5-fluorouracil (5-FU) 1,000 mg/m(2) days 1-4, and concurrent external beam radiotherapy (37.8 Gy). PLAFUR-4: between 1995 and 1998, 40 patients were treated with cisplatin (c-DDP) 60 mg/m(2) given as slow infusion (1-4 h) on days 1 and 29, plus 24-h continuous infusion i.v. 5-FU 1,000 mg/m(2), days 1-4 and 29-32 with concurrent external-beam radiotherapy (50.4 Gy). PLAFUR-5: between 1998 and 1999, 40 patients were treated with c-DDP 60 mg/m(2) given as slow infusion (during 1-4 h) on days 1 and 29, plus 24-h continuous infusion i.v. 5-FU 1,000 mg/m(2), days 1-5 and 29-33 with concurrent external-beam radiotherapy (50.4 Gy). RESULTS: Grade > or = 3 acute toxicity occurred in 14%, 5%, and 17% of patients treated in the FUMIR, PLAFUR-4, and PLAFUR-5 studies, respectively (p = 0.201). In the FUMIR, PLAFUR-4, and PLAFUR-5 studies, clinical response rate was 77%, 70%, and 83%, respectively. Tumor downstaging occurred in 57%, 68%, and 58% of patients, respectively. Pathologic complete response was recorded in 9% (FUMIR), 23% (PLAFUR-4), and 20% (PLAFUR-5) of patients. Sphincter-preserving surgery was feasible in 44% (FUMIR), 40% (PLAFUR-4), and 61% (PLAFUR-5) of patients having a distance between the anal-rectal ring and the lower pole of the tumor of 0-30 mm, and in 95%, 100%, and 100%, respectively, in those having a distance of 31-50 mm. Comparing FUMIR vs. PLAFUR, the clinical response rate was similar in the two series: a partial response was observed in 62/81 (77%) patients with FUMIR treatment, and in 61/80 (76%) patients with PLAFUR treatment. Tumor downstaging was observed in 46/81 (57%) patients and in 50/80 (68%) patients, respectively. The pathologic complete response rate was statistically higher in the PLAFUR series: 7/81 (9%) patients with FUMIR treatment and 17/80 (21%) patients with PLAFUR treatment (p = 0.04). Major downstaging (pT0+ pTmic+ pT1) in the FUMIR group was reported in 12/81 (15%) patients versus 31/80 (39%) patients in the PLAFUR group (p = 0.0006). The anal sphincter was preserved in 63/81 (78%) patients with FUMIR treatment and in 69/80 (86%) patients with PLAFUR treatment. The perioperative morbidity was statistically lower with PLAFUR: a perioperative morbidity was experienced by 20/81 (25%) patients with FUMIR treatment and by 9/80 (11%) patients with PLAFUR treatment (p = 0.042). CONCLUSION: In our experience, higher radiation dose (50.4 Gy vs. 37.8 Gy), a second course of concurrent 5-FU, and the use of c-DDP instead of MMC improved the pathologic response rate without increasing acute toxicity and perioperative morbidity. The use of 5-FU 5-day infusion (PLAFUR-5) resulted in higher toxicity with a similar response rate compared to 4-day infusion (PLAFUR-4).

Standardization of the comet assay technique on FRTL5 cells.

The comet assay is a sensitive and rapid method for DNA strand break detection in individual cells. The principle of break detection, using either the alkaline or neutral version of the assay, makes it a good technique for studying both double and single strand DNA breaks. Furthermore, the possibility of following DNA damage at different time moments also makes it possible to investigate the cell repair mechanisms. This explains why in the last few years there has been a tremendous increase in the number of laboratories which started to use this technique. The technique was first created for lymphocyte cells and later on has been used on many other cell types, growing both in suspension and adherent. To date, no one has applied this technique on normal differentiated endocrine cells, such as FRTL5 cells (Fisher Rat Thyroid Cells). The aim of this study has been to standardize the alkaline version of the Comet Assay technique on FRTL5 cells by studying the kinetics of DNA-damage and DNA-repair after different doses of UV-C (254 nm). FRTL-5 cells not only resulted very sensitive to UV-C (p<0.05 at 5 J/m2), but were also able to repair most of their DNA damage very rapidly (within one hour) as shown by a significant exponential regression in comet length. Finally, the successful measurement of biomarkers of UV-C on thyroid cells established the comet assay as a valuable tool in measurement of DNA damage and repair. Any radiation, or other damaging agents, interacting with living organisms could cause DNA damages which, depending upon dosages and kinetics of exposure, may or may not be completely repaired.

Radiation-dependent apoptosis on cultured thyroid cells.

Aim of this investigation is the study of the modifications and the DNA damage occurring in thyroid cells exposed to radiation. The FRTL-5 rat thyroid cell strain has been chosen for this study. Objects of this research are both Ionizing radiation, of fundamental interest for space missions, and the UV radiation, (also mutagen and frequent cause of several cancer forms). The present study of UV radiation represents a preliminarily tool to investigate the biological radiation damage. FRTL-5 cells have been irradiated with doses of UV-C (254 nm wavelength) ranging from 15 to 80 Joule/m2. The DNA damage has been analyzed with the 'DNA ladder by gel electrophoresis' technique. DNA has been extracted at 24 and 48 hours from irradiation. At 24h the apoptotic process is not detectable. At 48 h from irradiation, cells show the characteristic signs of apoptosis. The lower dose to which the apoptotic process is detectable, corresponds to 20 Joule/m2. At the higher doses a bigger percentage of cells undergoes apoptosis. These data confirms that the FRTL-5 biological system is particularly suitable for further studies on the biological mechanisms of radiation damage.

A new model of human aortic endothelial cells in vitro.

Vascular endothelial cells play an important role in coagulation regulation of vascular tone and in a variety of synthetic and metabolic functions. Endothelial cells also have a pivotal role in immunological diseases atherogenesis and tumor angiogenesis. Endothelial cells are often used as system to study the pathophysiology of late complications in diabetes mellitus atherosclerotic damages and leukocyte adhesion in inflammatory diseases. Most of the studies have been performed on primary arterial and venous endothelial cell cultures with problems such as availability of autoptic material and reproducibility of cell cultures. We have isolated and characterized a novel system of proliferating long-term cultures of human aortic endothelial cells that maintain their differentiated characteristics for many generations in vitro. They produce antithrombotic and thrombotic factors such as t-PA and PAI-1 and respond to TNFalpha, an important factor correlated with the inflammatory process by modifying growth characteristics by producing cytokines such as GM-CSF by expressing ICAM-1 on the surface and by producing large amounts of nitric oxide and endothelin. This new system may be very useful to understand and study the molecular mechanisms involved in many vascular alteration pathologies and in the aging process.

Transcriptional regulation of the MHC II gene DRA in untransformed human thyrocytes.

MHC class II molecules are heterodimeric, polymorphic transmembrane glycoproteins physiologically expressed on cells of the immune system and pathologically expressed on the affected target cells of autoimmunity. Their function is to present processed peptides to antigen-specific CD4(+) T cells. To understand the molecular mechanism of the regulation of class II genes in autoimmune target cell thyrocytes, we investigated the transcriptional regulation of DRA on untransformed, differentiated human thyroid cells following IFN-gamma stimulation, which is potentially relevant to the inappropriate class II expression found in Graves' disease. Data from this study show that IFN-gamma enhances a promoter Y box binding protein and induces an X box binding protein in untransformed thyrocytes, but not in SV-40-transfected thyrocytes. Initial characterization of the proteins has indicated that the Y box binding protein is approximately 132 kDa in size while the X box binding protein binds to the X2 region and is approximately 116 kDa. The X box binding protein may correspond to poly(ADP-ribose) polymerase, a recently described component of the X2 box binding protein, X2BP. In addition, the signal transducer and activator of transcription 1alpha protein (STAT1alpha) is also induced by IFN-gamma in these cells. These results further suggest that there are differences in class II gene regulation between differentiated cells and transformed cell lines.

Thyroid-specific gene expression is differentially influenced by intracellular glutathione level in FRTL-5 cells.

Alteration of the redox potential has been proposed as a mechanism influencing gene expression. Reduced glutathione (GSH) is one of the cellular scavengers involved in the regulation of the redox potential. To test the role that GSH may play in thyroid cells, we cultured a differentiated rat thyroid cell strain (FRTL-5) in the presence of L-buthionine-(S,R)-sulfoximine (BSO). BSO affects GSH synthesis by irreversibly inhibiting gamma-glutamylcysteine synthetase (EC 6.3.2.2), a specific enzyme involved in GSH synthesis. BSO-treated FRTL-5 cells show a great decrease in the GSH level, whereas malondialdehyde increases in the cell culture medium as a sign of lipid peroxidation. In these conditions the activity of two thyroid-specific promoters, thyroglobulin (Tg) and thyroperoxidase (TPO), is strongly reduced in transient transfection experiments. As both Tg and TPO promoters depend upon the thyroid-specific transcription factors, thyroid-specific transcription factor-1 (TTF-1) and Pax-8 for full transcriptional activity, we tested whether reduction of GSH concentration impairs the activity of these transcription factors. After BSO treatment of FRTL-5 cells, both transcription factors fail to trans-activate the respective chimerical targets, C5 and B-cell specific activating protein promoters, containing, respectively, multimerized TTF-1- or Pax-8-binding sites only as well as the Tg and TPO natural promoters. Northern analysis revealed that endogenous Tg messenger RNA (mRNA) expression is also reduced by BSO treatment, whereas endogenous TPO expression is not modified. Furthermore, the Pax-8 mRNA steady state concentration does not change in BSO-treated cells, whereas TTF-1 mRNA slightly decreases. Immunoblotting analysis of FRTL-5 nuclear extracts does not show significant modification of the Pax-8 concentration in BSO-treated cells, whereas a decrease of 25% in TTF-1 protein is revealed. Furthermore, BSO treatment decreases the DNA-binding activity to the respective consensus sequence of both transcription factors. Finally, different mechanisms seem to act on TTF-1 and Pax-8 functional impairment in BSO-treated cells. Indeed, with a lowered GSH concentration, the overexpressed Pax-8 still activates transcription efficiently, whereas, on the contrary, the overexpressed TTF-1 does not recover its transactivation capability when the respective chimerical target sequences are used (C5 and BSAP). When the natural Tg and TPO promoter sequences are used, overexpression of Pax-8 parallels the effect on both promoters observed using the chimeric target sequences, whereas overexpression of TTF-1 increases TPO promoter transcriptional activity only.

Preoperative chemoradiation with cisplatin and 5-fluorouracil for extraperitoneal T3 rectal cancer: acute toxicity, tumor response, sphincter preservation.

PURPOSE: To evaluate the impact of preoperative external radiation therapy intensified by systemic chemotherapy including bolus cisplatin (c-DDP) and 4-day infusional 5-fluorouracil (PLAFUR-4) on tumor response and sphincter preservation in patients with extraperitoneal T3 rectal cancer with acceptable toxicity, and to compare the results to our previous experience with bolus mitomycin c (MMC) and 4-day infusion 5-FU (FUMIR). METHODS AND MATERIALS: Between October 1995 and March 1998, 40 consecutive patients with resectable extraperitoneal adenocarcinoma of the rectum were treated with preoperative chemoradiation: slow infusion i.v. c-DDP, 60 mg/m2, day 1 and 29 plus 24-h continuous infusion i.v. 5-fluorouracil (5-FU) 1000 mg/m2, days 1-4 and 29-32, and concurrent external beam radiotherapy (45 Gy whole pelvis followed by 5.4 Gy boost). All but 3 patients had T3 disease. Surgery was performed 6-8 weeks after the end of chemoradiation. RESULTS: No patient had Grade 4 acute toxicity. Grade 3 hematological toxicity was observed only in 2 (5%) patients. No patient had major gastrointestinal, skin, or urological acute toxicity. All patients had radical surgery. There was no perioperative mortality; perioperative morbidity rate was 12%. Overall, 23% (9 of 40) of patients had a complete pathological response and 10% (4 of 40) of patients had rare isolated residual cancer cells (Tmic). Comparing the stage at the diagnostic workup with the pathological stage, tumor downstaging was observed in 27 (68%) patients; nodal status downstaging was detected in 24 (60%) patients. Thirty-four (85%) patients had a sphincter-saving surgical procedure. In 4 of 10 (40%) patients who were definitive candidates for an abdominoperineal resection (APR), the sphincter was preserved, as it was in 13 of 13 (100%) probable candidates. Lengthening of the distance between the anorectal ring and the lower pole of the tumor > or =20 mm was observed in 9 (23%) patients. None of the patients had soilage after the sphincter-saving procedure. In our previous experience with FUMIR the complete pathological response was 9%, the sphincter-saving surgical procedure was performed in 66% cases, and the Grade 3+ toxicity was observed in 13% of patients. CONCLUSIONS: The addition of c-DDP to 5-FU (PLAFUR-4) in a neoadjuvant radiochemotherapy schedule improved the pathological response rate in comparison with our previous experience. Toxicity was low indeed, thus we commenced another study adding one more day of 5-FU infusion (PLAFUR-5) to further improve our results.

HLA-DMB expression by thyrocytes: indication of the antigen-processing and possible presenting capability of thyroid cells.

Expression of HLA class II molecules on thyrocytes is a characteristic feature of autoimmune thyroid disease and may lead the thyroid cells to present autoantigens to CD4+ T lymphocytes. Since HLA-DM is a critical molecule in class II-restricted antigen processing and presentation, we assessed the expression of HLA-DMB, -invariant chain (Ii), class II transactivator (CIITA) and DRA in an untransformed, pure thyrocyte strain HTV-59A. Here we report that both HLA-DMB mRNA and the protein are expressed in thyrocytes and that CIITA expression is enhanced by interferon-gamma (IFN-gamma) treatment and occurs before DMB, Ii and DRA up-regulation, suggesting CIITA expression is a requirement for antigen processing in thyrocytes. These results indicate that thyrocytes are capable of antigen processing and possibly antigen presentation to T cells.