Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “TME”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 577 records · Page 32Linked to original sources

Nutritive value of high-oil corn grown under semi-arid conditions and its impact on broiler performance and carcass composition.

A series of experiments was conducted to evaluate nutritive value of a high-oil corn (HOC) cultivar, grown under semiarid conditions, and its impact on performance and carcass characteristics of male broilers raised to market age. Conventional corn (CC) and HOC used in this research were produced under similar semi-arid conditions. By using a glucose containing reference diet in Experiment 1, the AMEn of CC, as determined on 11-d-old male broilers, was lower (P < 0.05) than that of HOC (3,541 vs. 3,669 kcal/kg DM). The TME, TMEn, and true amino acid availability of CC and HOC were determined in Experiment 2 through individual precision feeding of eight intact mature roosters per ingredient. The TMEn of HOC was significantly higher than that of CC (4,126 vs. 3,870 kcal/kg DM), but true availability of amino acids was comparable for both cultivars. By using the CP and TMEn values determined in Experiment 2, two corn soybean meal starter and grower diets, containing no added fat, were prepared in Experiment 3, in which HOC replaced CC. Diets were provided ad libitum in five replicates to 5-d-old male broilers with eight birds per replicate until market age. Broiler performance, carcass yield, and carcass composition were comparable between both corn cultivars. Birds on HOC diet, however, deposited more (P < 0.05) abdominal fat (0.695%) than those on CC diet (0.575%). The results indicated that the extra calories derived from HOC could have been funneled primarily toward abdominal fat pad deposition rather than increased growth.

Adipose Tissue↗

Centrally bradykinin B2-receptor-induced hypertensive and positive chronotropic effects are mediated via activation of the sympathetic nervous system.

OBJECTIVE: The presence of bradykinin B2 receptors in the cardiovascular regulatory centres of the brain indicates that increase in mean arterial pressure (MAP) and heart rate after intracerebroventricular (i.c.v.) injections of bradykinin is mediated via stimulation of sympathetic nervous system. METHODS: Adult Wistar- Kyoto (WKY) rats were instrumented chronically with an i.c.v. cannula, and the catheters were placed into the femoral artery and vein. Increasing doses of bradykinin (1 -300 pmol) were given i.c.v. and (i) MAP and heart rate, (ii) plasma dopamine, noradrenaline and adrenaline, and (iii) plasma arginine vasopressin (AVP) levels were determined. In addition, following blockade of peripheral alpha1 -adrenoceptors with prazosin (50 and 250 microg/kg i.v.) beta1-adrenoceptors with atenolol (10 mg/kg i.v.) or V1 -receptors with TMe-AVP (Manning compound) (10 microg/kg i.c.v. and 100 microg/kg i.v.) the effects of bradykinin (100 pmol i.c.v.) on MAP and heart rate were determined. RESULTS: Bradykinin increased MAP and heart rate dose-dependently. The pressor effects of 100 pmol bradykinin i.c.v. were completely blocked by pretreatment with the specific B2 receptor antagonist Hoe 140 (3 pmol, i.c.v.). There was no change in plasma dopamine, noradrenaline, adrenaline or AVP levels after increasing doses of bradykinin. However, peripheral blockade of alpha1- and beta1-adrenoceptors reduced the bradykinin-induced increase in MAP and heart rate, whereas central and peripheral V1 receptor blockade did not alter the cardiovascular responses to i.c.v. bradykinin. CONCLUSION: Our data suggest that the hypertensive and positive chronotropic effects induced by i.c.v. bradykinin are due to stimulation of sympathoneuronal rather than sympathoadrenal pathway in vivo.

Adrenergic alpha-1 Receptor Antagonists↗

Analysis of three amphibian populations with quarter-century long time-series.

Amphibians are in decline in many parts of the world. Long tme-series of amphibian populations are necessary to distinguish declines from the often strong fluctuations observed in natural populations. Time-series may also help to understand the causes of these declines. We analysed 23-28-year long time-series of the frog Rana temporaria. Only one of the three studied populations showed a negative trend which was probably caused by the introduction of fish. Two populations appeared to be density regulated. Rainfall had no obvious effect on the population fluctuations. Whereas long-term studies of amphibian populations are valuable to document population declines, most are too short to reveal those factors that govern population dynamics or cause amphibian populations to decline.

Animals↗

Plants under Climatic Stress: II. Low Temperature, High Light Effects on Chloroplast Ultrastructure.

Mesophyll chloroplasts of the C(4)-pathway grasses Sorghum and Paspalum and of the C(3)-pathway legume soybean undergo ultrastructural changes under moderate light intensities (170 w.m(-2), 400-700 nanometers) at a tme when photosynthesis is much reduced by low temperature (10 C). The pattern of ultrastructural change was similar in these species, despite some differences in the initial sites of low temperature action on photosynthesis and differences in their mechanisms of CO(2) fixation. Starch grains in the chloroplasts rapidly reduce in size when chilling stress is applied. At or before the time starch grains completely disappear the membranes of the individual stromal thylakoids close together, reducing the intraspace between them while the chloroplast as a whole begins to swell. Extensive granal stacking appears to hold the thylakoids in position for some time, causing initial swelling to occur in the zone of the peripheral reticulum, when present. At more advanced stages of swelling the thylakoid system unravels while the thylakoid intraspaces dilate markedly. Initial thylakoid intraspace contraction is tentatively ascribed to an increase in the transmembrane hydrogen ion gradient causing movement of cations and undissociated organic acids from the thylakoid intraspace to the stroma. Chloroplast swelling may be caused by a hold-up of some osmotically active photosynthetic product in the chloroplast stroma. After granal unraveling and redilation of the thylakoid intraspaces, chloroplasts appear similar to those isolated in low salt hypotonic media. At the initial stages of stress-induced ultrastructural change, a marked gradient in degree of chloroplast swelling is seen within and between cells, being most pronounced near the surface of the leaf directly exposed to light.

Journal Article↗

The circular stapling device as a risk factor for anastomotic leakage.

AIM: To investigate the relation between the type of circular stapler and anastomotic leak in rectal cancer surgery. BACKGROUND: During the past decades results from rectal cancer surgery have improved considerably regarding risk of local recurrence and survival. Two main paradigm changes are considered to be the cause for this: the introduction of total mesorectal excision (TME) and the increasing use of radiotherapy. However, rectal cancer surgery is associated with an unacceptably high frequency of complications of which anastomotic leak is one of the most severe ones. The hypothesis was raised that the choice of stapler influenced the leakage rates. METHODS: A questionnaire was sent to all departments of surgery (n = 66) performing rectal cancer surgery in Sweden to determine the choice of circular stapler when performing anterior resection for rectal cancer. These data were linked to the Swedish Rectal Cancer Registry for the period 1995-99. RESULTS: A total of 3316 patients had an anterior resection. The choice of circular stapling device was determined in 70% of the cases. When stapler A was used, the leakage rate was 11% whereas it was 7% when stapler B was used (P = 0.0039). In the cases where it was impossible to determine which stapler had been used the leakage rate was 8%. CONCLUSION: Quality control is an important part of medicine and the present study suggests that it also must include surgical instruments. A prospective randomised study is needed to confirm the results.

Adult↗

Almost all five year disease free survivors are cured following rectal cancer surgery, but longer term follow-up detects some late local and systemic recurrences.

BACKGROUND: The necessity, timing and benefits of follow-up after rectal cancer surgery remain controversial, with two years traditionally considered adequate to detect most local recurrences. This unit has a policy of lifetime follow-up, and this paper investigates, at 23 years, the value of prolonged surveillance. METHOD: Six hundred and sixty consecutive patients undergoing surgery for rectal cancer were prospectively followed-up between 1978 and 2002, and local or systemic recurrence recorded. This analysis was performed on the 509/660 (76%) patients who underwent potentially curative surgery. RESULTS: Total mesorectal excision (TME) was performed in 422/509 (83%) patients, mesorectal transection in 78 (15%), and local excision in 9 (2%). Follow-up ranged from 1 to 23 years (mean = 9.7). Seven (1.4%) patients had local recurrence alone, 11 (2.2%) local plus systemic, and 86 (17%) systemic recurrence alone. Of the local recurrences 3 (17%) became evident within 1 year, 9 (50%) within 2 years, 16 (89%) within 5 years, and 2 (11%) presented after 5 years, at 5.6 and 5.8 years. Of the systemic recurrences 26 (27%) became evident within 1 year, 57 (59%) within 2 years, 93 (96%) within 5 years, and 4 (4%) presented after 5 years at 5.3, 5.3, 5.4 and 7.9 years. CONCLUSION: This long-term surveillance of patients undergoing curative surgery for rectal cancer demonstrates that most local and systemic recurrences occur within 5 years. Almost half occurred more than 2 years after surgery. However, those centres wishing to set standards of care, or evaluate current or new therapies in rectal cancer treatment, should be aware that unexpected late recurrences occasionally develop.

Adult↗

Can the results of anorectal (abdominoperineal) resection be improved: are circumferential resection margins too often positive?

Carefully executed surgery for rectal cancer has reduced the incidence of local recurrence after restorative resection. Three recent large prospective series have confirmed the perception of a higher positive circumferential resection margin (CRM) rate after abdominoperineal resection. Tumour spread is different for low tumours and the surgical technique of abdominoperineal resection, perhaps better known as anorectal excision, may vary between surgeons. There is a need to redefine the place of anorectal excision and the contribution that can be made by pre-operative chemoradiation and/or extended surgery to reduce local recurrence and increase survival. Defined surgery, validated by histopathological assessment, as applied to TME surgery, would determine whether the perceived higher rates are due to the differences in routes of tumour spread or to surgically related variables. Unnecessary R1 or R2 resections and operative perforation can be minimized by an understanding of the surgical anatomy, the pattern of spread and difference in operative technique between anorectal excision and a low restorative operation. Surgical technique to maximize R0 resection should be based on a detailed understanding of the pelvic fascia and the levator ani and the use of pre-operative imaging to define lines of excision. With the adoption of even lower restorative resection (intersphincteric) there is a need to reassess the method of anorectal excision. This may be achieved by histopathological assessment of CRM positivity and MDT audit to improve results. Clinical trials are essential.

Abdomen↗

Rectal cancer treatment of the elderly.

OBJECTIVE: Life expectancy and incidence of rectal cancer have been increasing. The purpose of this study was to evaluate rectal cancer treatment among very old patients. METHODS: This prospective national cohort study includes all 4875 rectal cancer patients in Norway aged over 65 years treated between November 1993 and December 2001. Patients aged 65-74, 75-79, 80-84 and over 85 years were compared for patient-, tumour- and treatment-characteristics and relative survival. Two thousand eight hundred and forty patients treated for cure with major surgery and TME technique were further evaluated for postoperative mortality, five-year local recurrence, distant metastasis and disease-free survival. RESULTS: There were more palliative surgery and local procedures and less surgery for cure (47%vs 77%, P < 0.001) for patients over 85 years compared to younger patients. Five-year relative survival was 36% for patients aged over 85 years compared to 49% for patients 80-84 years and 60% for patients 65-74 years. Among patients treated for cure with major surgery the rate of anterior resection decreased by age (67%vs 46%, P < 0.001). Postoperative mortality increased from 3% to 8% (P < 0.001). There were no significant differences in the rates of five-year local recurrence, distant metastasis or relative survival. CONCLUSION: Although a slight increase in postoperative mortality, major rectal cancer surgery can be performed in very old patients. These patients had similar rates of local recurrence, distant metastasis and relative survival as younger patients.

Adenocarcinoma↗

Nationwide quality assurance of rectal cancer treatment.

OBJECTIVE: The purpose of this prospective study was to examine the influence of the efforts for nationwide quality assurance of rectal cancer treatment. The study focuses on local recurrence and overall survival. METHODS: This study includes all 3388 Norwegian patients with a rectal cancer within 15 cm from the anal verge treated with curative intent in the period November 1993-December 1999. A comprehensive educational programme was established, and training courses were arranged in different Health Regions demonstrating the TME technique. A specific Rectal Cancer Registry enabled the monitoring of outcome of rectal cancer treatment for single hospitals. Radiotherapy was given to 10% of the patients. RESULTS: The risk of local recurrence has been significantly reduced, so that in 1999 the level was 50% below that observed in 1994 (Hazard ratio (HR)1999=0.5; 95% CI 0.4-0.8, P=0.002). Similarly, during 1998, the mean national overall survival was significantly improved, compared to the rate in 1994 (HR1998=0.8; 95% CI 0.6-1.0, P=0.014). CONCLUSION: The prognosis for rectal cancer can be improved by increased organizational focus on rectal cancer treatment and by establishing a rectal cancer registry monitoring treatment standards throughout the country.

Aged↗

A continuous 4D motion model from multiple respiratory cycles for use in lung radiotherapy.

Respiratory motion causes errors when planning and delivering radiotherapy treatment to lung cancer patients. To reduce these errors, methods of acquiring and using four-dimensional computed tomography (4DCT) datasets have been developed. We have developed a novel method of constructing computational motion models from 4DCT. The motion models attempt to describe an average respiratory cycle, which reduces the effects of variation between different cycles. They require substantially less memory than a 4DCT dataset, are continuous in space and time, and facilitate automatic target propagation and combining of doses over the respiratory cycle. The motion models are constructed from CT data acquired in cine mode while the patient is free breathing (free breathing CT - FBCT). A "slab" of data is acquired at each couch position, with 3-4 contiguous slabs being acquired per patient. For each slab a sequence of 20 or 30 volumes was acquired over 20 seconds. A respiratory signal is simultaneously recorded in order to calculate the position in the respiratory cycle for each FBCT. Additionally, a high quality reference CT volume is acquired at breath hold. The reference volume is nonrigidly registered to each of the FBCT volumes. A motion model is then constructed for each slab by temporally fitting the nonrigid registration results. The value of each of the registration parameters is related to the position in the respiratory cycle by fitting an approximating B spline to the registration results. As an approximating function is used, and the data is acquired over several respiratory cycles, the function should model an average respiratory cycle. This can then be used to calculate the value of each degree of freedom at any desired position in the respiratory cycle. The resulting nonrigid transformation will deform the reference volume to predict the contents of the slab at the desired position in the respiratory cycle. The slab model predictions are then concatenated to produce a combined prediction over the entire region of interest. We have performed a number of experiments to assess the accuracy of the nonrigid registration results and the motion model predictions. The individual slab models were evaluated by expert visual assessment and the tracking of easily identifiable anatomical points. The combined models were evaluated by calculating the discontinuities between the transformations at the slab boundaries. The experiments were performed on five patients with a total of 18 slabs between them. For the point tracking experiments, the mean distance between where a clinician manually identified a point and where the registration results located the point, the target registration error (TRE), was 1.3 mm. The mean distance between a manually identified point and the models prediction of the point's location, the target model error (TME), was 1.6 mm. The mean discontinuity between model predictions at the slab boundaries, the Continuity Error, was 2.2 mm. The results show that the motion models perform with a level of accuracy comparable to the slice thickness of 1.5 mm.

Artifacts↗

Axon destruction and adrenergic systems mediate pressor responses after AV3V lesions.

These studies investigated the neural tissue and peripheral mechanism mediating the transient pressor response following electrolytic ablation of the periventricular tissue surrounding the anteroventral third ventricle (AV3V) of the rat. Arterial blood pressure was monitored in conscious animals for 2 h following either microinjection of kainic acid (AV3V-KA) or electrolytic lesions (AV3V-X) in the AV3V region or control procedures (Cont). Blood pressure did not change in AV3V-KA (4 +/- 3 mmHg) or Cont rats but significantly increased in AV3V-X animals (20 +/- 4 mmHg). The pressor response following AV3V-X was not altered by pretreatment with MK-422 (converting-enzyme inhibitor), TMe-AVP (vasopressin antagonist), or hexamethonium (ganglionic blocker). However, intravenous administration of prazosin (alpha-adrenergic blocker) or bilateral adrenalectomy abolished the increase in blood pressure. Furthermore, plasma concentrations of norepinephrine were significantly higher in AV3V-X rats (1,125 +/- 150 pg/ml) compared with Cont animals (322 +/- 83 pg/ml) following treatment. These data indicate that the acute hypertensive response following AV3V-X is caused by the destruction of fibers of passage and results from circulating catecholamines of adrenal origin.

Angiotensin II↗

Reprogramming of TLR-Ferroptosis Signaling and Immunometabolic Pathways Overcomes Myeloid Suppression to Improve Checkpoint Blockade in Prostate Cancer.

UNLABELLED: The limited efficacy of immunotherapies in advanced prostate cancer stems from a tumor microenvironment (TME) in which myeloid-driven immune suppression, stromal remodeling, and metabolic barriers converge to limit antitumor immunity. In this study, we characterized the immunometabolic properties of an ultrasmall prostate-specific membrane antigen-targeting silica particle therapy as a first-in-class strategy to reprogram the Toll-like receptor (TLR)-ferroptosis axis in MYC-driven prostate cancer. As single agents, these particles suppressed lipid and steroid biosynthesis, disrupted lipid peroxidation control, and impaired nutrient flux, sensitizing tumors to ferroptosis. Coordinated redox remodeling, stromal reprogramming, and innate immune activation reversed myeloid suppression and promoted CD8+ T-cell infiltration. When combined with CSF-1R inhibition and immune checkpoint blockade, the particles suppressed tumor growth, extended survival beyond 100 days, and achieved up to 50% complete remission in MYC-overexpressing models. These findings position TLR-ferroptosis axis remodeling as a mechanistic blueprint for rational, particle-driven immunotherapies with broad translational potential in prostate cancer and other immunologically refractory malignancies. SIGNIFICANCE: Clinically validated, PSMA-targeted ultrasmall core-shell silica particles reprogram immunometabolic pathways via a TLR-ferroptosis axis, enabling tumor microenvironment remodeling and potentiating checkpoint blockade in prostate cancer, with translational implications for treatment-resistant disease.

Male↗

Brainstem auditory evoked potentials of panic disorder patients.

Panic attacks are subjectively reported by patients as a cluster of autonomic nervous symptoms. Taken together with the evidence from pharmacological studies focusing on the locus ceruleus and the dorsal raphe nuclei, the hypothesis of brainstem involvement in panic attacks is of major interest. Functional evaluation of the brainstem is carried out using electrophysiological recordings, such as the brainstem evoked potentials. We have investigated the pathophysiology of these parameters in 16 patients fulfilling the DSM III-R criteria for panic disorder (8 females and 8 males) in comparison to a group of 10 normal controls. The patients were found to have two electrophysiological variables significantly different from controls: (a) N3 latency tme was reduced (p < 0.05) and (b) the N3-5 interval was prolonged (p < 0.05). The N3 latency period significantly correlated with the Hamilton Anxiety Scale scores (p < 0.005). N3 is a peak reflecting pontine activation, where the locus ceruleus is located. The N3-5 interval reflects evoked potential passage from the pons to the midbrain. In conclusion, our results support previous studies indicating a dysfunction of the locus ceruleus possibly causing disruption of pons-midbrain transmission in patients suffering from panic disorder.

Adult↗

Tidal breathing analysis as a measure of airway obstruction in children three years of age and older.

This study was designed to evaluate the value and applicability of tidal breathing pattern analysis to assess airflow obstruction in young children. The time needed to reach maximal tidal expiratory flow (TME) divided by total expiratory time (TE) was measured in 228 healthy children 3 to 11 yr of age, 64 patients with asthma, and 12 children with cystic fibrosis. In 70 patients both TME/TE and forced maximal expiratory flow volume (MEFV) parameters were measured. The mean TME/TE in healthy subjects was 43.0 +/- 7.6%. The within-subject reproducibility was high (repeatability index, 5.3%). In the asthmatic patients the mean TME/TE was significantly lower (30.0 +/- 8.2%, p < 0.001), and it increased to 36.5 +/- 7.9% after bronchodilation (n = 44, p < 0.001). The TME/TE level of the subgroup of patients with asthma and FEV1/FVC > or = 0.80 was lower when compared with age-matched normal subjects (30.9 +/- 8.5, p < 0.0001), but it was in a higher range when compared with asthmatics with FEV1/FVC < 0.80 (25.9 +/- 7.9, p < 0.001). In the cystic fibrosis group the mean TME/TE was 27.4 +/- 10.7% without a significant change after bronchodilation. TME/TE correlated significantly with MEFV parameters. Tidal breathing analysis proved easy to perform in children older than 3 yr of age. The TME/TE ratio may be a reliable and simple indicator for airway obstruction.

Airway Resistance↗

COL5A1 in the tumor microenvironment predicts the prognosis of head and neck cancer.

ObjectivesThis study aims to investigate the significance of tumor microenvironment (TME)-related genes and signal transduction pathways in head and neck cancer (HNC).MethodsGene expression and clinical data of HNC patients were obtained from the Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) were screened through a multi-step filtration approach to obtain candidate predictors. The biological role of COL5A1 in HNC was verified through rigorous bioinformatic analysis, experimental validation using quantitative real-time PCR (qRT-PCR), immunohistochemical (IHC) analysis from HNC samples, and IHC data from the Human Protein Atlas (HPA) database.ResultsCOL5A1 was significantly upregulated in HNC tissues and cell lines. High COL5A1 expression was significantly associated with advanced tumor grade (P&#x2009;<&#x2009;.05) and shorter survival (TCGA: P&#x2009;<&#x2009;.001; GSE42743: P&#x2009;=&#x2009;.004). COL5A1 was an independent prognostic indicator (univariate analysis: HR&#x2009;=&#x2009;1.324, P&#x2009;=&#x2009;.001; Multivariate analysis: HR&#x2009;=&#x2009;1.326, P&#x2009;=&#x2009;.005). It was enriched in pathways related to tumor invasion and immune responses, and its expression was associated with decreased levels of CD8+ T cells and increased levels of macrophages and neutrophils. Spatial distribution analysis revealed higher expression at the tumor's leading edge (vs. tumor core: P&#x2009;<&#x2009;.001). COL5A1 expression is associated with tumor stage, with more pronounced expression in advanced-stage tumors.ConclusionCOL5A1 represented a novel potential prognostic indicator and therapeutic target in an HNC database sample, as its expression is closely linked to tumor progression, immune cell infiltration, and adverse clinical outcomes. These findings, primarily derived from squamous cell carcinoma-dominated cohorts, warrant further functional validation.

Humans↗

Cell-type specific activation of the cGAS-STING pathway in tumor immunotherapy: mechanisms and therapeutic implications.

BACKGROUND: The cyclic GMP&#x2013;AMP synthase&#x2013;stimulator of interferon genes (cGAS&#x2013;STING) pathway acts as a pivotal innate immune sensor that detects cytosolic DNA and links genomic instability to antitumor immune activation. Therapeutic activation of this pathway has garnered substantial interest as a strategy to enhance cancer immunotherapy by promoting dendritic cell maturation, augmenting antigen presentation, and facilitating cytotoxic lymphocyte infiltration. However, the functional outcomes of cGAS&#x2013;STING signaling are highly context dependent and influenced by both cell type and tumor microenvironmental (TME) conditions. MAIN BODY: Recent advances in single-cell and spatial transcriptomic profiling have revealed profound heterogeneity in cGAS&#x2013;STING activation across distinct cellular and regional compartments within tumors. Acute and spatially restricted activation of the pathway can elicit potent antitumor immune responses, whereas chronic or dysregulated signaling may promote immune tolerance and tumor progression. Moreover, metabolic stress, epigenetic silencing, and microenvironmental immunosuppressive factors such as TGF-&#x3b2; and IL-10 can further modulate STING activity, leading to resistance to immunotherapy. Current translational efforts focus on next-generation STING agonists, nanoparticle-based delivery systems, and rational combination strategies with immune checkpoint blockade and metabolic modulators to overcome tumor-intrinsic resistance and minimize systemic toxicity. CONCLUSIONS: Understanding the cell-type-specific and spatial dynamics of cGAS&#x2013;STING signaling is crucial for the rational design of precision immunotherapies. Future research should emphasize context-dependent modulation of STING activity to maximize therapeutic benefit while limiting adverse effects. Integrating multi-omics technologies and spatially guided drug delivery may ultimately enable personalized modulation of the cGAS&#x2013;STING axis, transforming it into a clinically effective and safe strategy for cancer immunotherapy.

Humans↗

Prognostic significance of circumferential resection margin following total mesorectal excision and adjuvant chemoradiotherapy in patients with rectal cancer.

BACKGROUND: This study was designed to evaluate the prognostic value of circumferential resection margin (CRM) in rectal cancer patients who underwent curative resection with adjuvant chemoradiotherapy (CRT). METHODS: We studied 504 patients who underwent total mesorectal excision with adjuvant CRT for rectal cancer between 1997 and 2001. The patients were divided into two groups: a negative CRM group (CRM > 1 mm) and a positive CRM group (CRM <or= 1 mm). The survival rates, local recurrence rates, and systemic recurrence rates were compared between groups. RESULTS: The negative CRM group had 460 patients and the positive CRM group had 44 patients. The 5-year local and systemic recurrence rates were 11.3 and 25.3%, respectively, in the negative CRM group and 35.2 and 60.8% in the positive CRM group, respectively. The cancer-specific 5-year survival rates for the two groups were 72.5 and 26.9% (P < .001), respectively. CRM was found to be an independent prognostic factor by multivariate analyses which were adjusted for known outcome predictors (P < .001). CONCLUSION: Oncological outcome for patients in the positive CRM group is less favorable than for those in the negative CRM group. Adjuvant CRT is not a definite treatment modality that can be used to compensate for a positive CRM following TME and adjuvant CRT in patients with TNM stage II or III rectal cancer.

Adenocarcinoma↗

[Transcription factors responsible for megakaryocyte-specific gene expression].

Megakaryocytes are the hematopoietic precursors of platelets, which play an essential role in thrombosis and hemostasis. Platelet factor 4 (PF4) is expressed exclusively in megakaryocytes and platelets and serves as a lineage-specific marker of megakaryocytic differentiation. We previously characterized a number of upstream enhancer and repressor elements and demonstrated that GATA-1 and ETS-1 are important for PF4 gene expression. Recently, we have determined the novel regulatory element termed "TME" in the PF4 promoter and identified a group of binding proteins from megakaryocytic HEL cells. Here we review the function of these proteins in PF4 gene expression and discuss megakaryocyte-specific gene expression and megakaryocytepoiesis.

Animals↗