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Background: Pulmonary spindle cell carcinoma (PSCC), a highly malignant tumor, often exhibits cell pleomorphism, a histopathological characteristic. Owing to its extremely low incidence, atypical imaging and clinical presentations, and insufficient awareness among clinicians, PSCC is often misdiagnosed, which results in delays in treatment. Herein, we reported a rare case of PSCC that was initially misdiagnosed as granulomatous inflammation. Case Presentation: A 66-year-old male visited a local hospital with symptoms such as cough and hemoptysis. A computed tomography (CT) scan of the chest revealed a mass in his right lung, and no mediastinal lymphadenopathy was observed. Bronchoscopy showed no major abnormalities, and the results of fine needle aspiration biopsy showed granulomatous inflammation. Even though the patient received anti-infection treatment, his symptoms did not improve markedly. After two months, a follow-up CT scan of the lung showed a noticeably enlarged mass accompanied by multiple instances of mediastinal lymphadenopathy in the upper lobe of the right lung. Consequently, he underwent a second CT-guided lung biopsy at our hospital. The pathology report indicated PSCC. Due to financial constraints, genetic testing was not performed. Given his poor overall physical condition, the patient was unable to undergo systemic chemotherapy and instead received palliative radiotherapy. The prescribed radiotherapy dose for the right upper lobe lung cancer and multiple metastatic lymph nodes was 60 Gy, administered in 30 fractions. Unfortunately, he failed to adhere to scheduled follow-ups and succumbed to the disease 6 months later, as confirmed during a telephone follow-up. Conclusion: PSCC is a rare but highly malignant lung cancer. Multiple pathological biopsies are necessary to accurately and promptly diagnose the disease, which is crucial for early treatment intervention as well as improving patient prognosis.
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Clathrin is one of the leading players in the endocytic process during oocyte maturation. Immunofluorescence and transmission electron analysis on fully-grown germinal vesicle (GV) mouse oocytes shows Clathrin localization on the cortical region with three peculiar patterns: complete, incomplete, and half-moon. The first configuration is characterized by Clathrin lattices along the cortex; the second is represented by Clathrin lattices interrupted by invaginations forming coated vesicles as an indication of active endocytosis. The half-moon profile, the less frequent but the most interesting one, refers to Clathrin lattices distributed to one-half of the cell. The in vivo analysis of organelles' positioning and cytoplasmic rearrangements, performed to understand the possible relation between endocytosis and oocyte maturation, suggests that the half-moon pattern indicates those fully-grown oocytes that may have likely undergone Germinal Vesicle Breakdown, MI, and MII. Our results show that, before oocytes undergo maturation, Clathrin localizes on the side of the cell, opposite to future spindle migration, thus marking spindle orientation in mouse oocytes.
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Introduction: We have developed a risk-scoring model using gene expression levels related to mitotic spindle assembly (MSA) to predict the prognosis of liver cancer. Methods and results: Initially, we identified 470 genes related to MSA from public databases. Subsequently, through analysis of sequencing data from liver cancer patient samples in online databases, we identified 7 genes suitable for constructing the risk-scoring model. We validated the predictive accuracy and clinical utility of the model. Through drug sensitivity analysis, we identified SAC3D1 as a gene sensitive to the most common anti-tumor drugs among these 7 genes. We propose SAC3D1 as a significant target for future clinical treatment. Furthermore, we conducted in vivo and in vitro experiments to validate the relevance of SAC3D1 to MSA and found its significant impact on the PI3K/Akt signaling pathway and spindle function. Conclusion: Our research introduces a novel risk-scoring model that accurately predicts liver cancer prognosis. Additionally, our findings suggest SAC3D1 as a promising therapeutic target for hepatocellular carcinoma, potentially revealing new mechanisms underlying liver cancer development.
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Over the past decade, phase-targeted auditory stimulation (PTAS), a neuromodulation approach which presents auditory stimuli locked to the ongoing phase of slow waves during sleep, has shown potential to enhance specific aspects of sleep functions. However, the complexity of PTAS responses complicates the establishment of causality between specific electroencephalographic events and observed benefits. Here, we used down-PTAS during sleep to specifically evoke the early, K-complex (KC)-like response following PTAS without leading to a sustained increase in slow-wave activity throughout the stimulation window. Over the course of two nights, one with down-PTAS, the other without, high-density electroencephalography (hd-EEG) was recorded from 14 young healthy adults. The early response exhibited striking similarities to evoked KCs and was associated with improved verbal memory consolidation via stimulus-evoked spindle events nested into the up-phase of ongoing 1 Hz waves in a central region. These findings suggest that the early, KC-like response is sufficient to boost memory, potentially by orchestrating aspects of the hippocampal-neocortical dialogue.
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Stimulation acoustique , Électroencéphalographie , Consolidation de la mémoire , Humains , Mâle , Consolidation de la mémoire/physiologie , Femelle , Adulte , Jeune adulte , Sommeil/physiologie , Potentiels évoqués auditifs/physiologie , Volontaires sainsRÉSUMÉ
INTRODUCTION: Ultra-high static magnetic fields (SMFs) have unique advantages in improving medical and academic research. However, the research on the early embryo exposure of ultra-high SMFs is minimal, extensive exploration is indispensable in living organisms. OBJECTIVES: The present study was aimed to study the effects of ultra-high SMFs on the early embryonic division and development of Caenorhabditis elegans (C. elegans). METHODS: Early adult parents containing fertilized eggs in vivo were exposed to SMFs at intensities ranging from 4 T to 27 T. The number of mitotic cells in the reproductive glands of the P0 worms, early embryonic cell spindle localization, embryo hatching and the reproductive as well as developmental indicators of F1 and F2 nematodes were examined as endpoints. RESULTS: Our results indicated that ultra-high SMFs has no obvious effect on the germ cell cycle, while 14 T and 27 T SMFs significantly increased the proportion of multi-polar spindle formation in early embryonic cells, and reduced the developmental rate and lifespan of C. elegans exposed at the embryonic stage. Spindle abnormalities of early embryonic cells, as well as the down-regulation of genes related to asymmetric embryonic division and the abnormal expression of the non-muscle myosin NMY-2 in the division grooves played a critical role in the slowing down of embryonic development induced by ultra-high SMFs. CONCLUSIONS: This study provided novel information and a new sight for evaluating the biosafety assessment by exposure to ultra-high SMFs at the early embryonic stage in vivo.
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Small mammals are very popular companion animals, and the incidence of particular tumour types in these animals is the subject of extensive research. We carried out a retrospective and comparative analysis of the incidence of reproductive tract and mammary tumours and tumour-like lesions collected from 103 pet rabbits, 75 pet rats, 71 guinea pigs, 12 mice, 11 hamsters, eight African pygmy hedgehogs, four ferrets and two chinchillas. The results indicate that uterine tumours and tumour-like lesions are common in pet rabbits, guinea pigs and African pygmy hedgehogs. In pet rabbits, the most common uterine tumour was endometrial adenocarcinoma, while in guinea pigs benign lesions predominated (ie, leiomyoma, endometrial adenoma, cystic endometrial hyperplasia and deciduoma). Uterine tumours in African pygmy hedgehogs included adenosarcomas and endometrial polyps. Ovarian lesions were found only in guinea pigs (ovarian rete adenomas, rete cysts) and African pygmy hedgehogs (mostly granulosa cell tumours), while testicular tumours were diagnosed in pet rabbits, one pet rat and one guinea pig. Mammary tumours were common in pet rabbits, pet rats, guinea pigs, mice, hamsters and African pygmy hedgehogs. In pet rats, the most common mammary tumour was fibroadenoma, while in other animals carcinomas predominated. In guinea pigs and, to a lesser extent, in pet rats, a significant percentage of mammary tumours occurred in males. Guinea pigs seem to be predisposed to mammary tumours of ductal origin. This study describes for the first time uterine angioleiomyoma in the pet rabbit and mammary spindle cell carcinoma in the Djungarian hamster and chinchilla.
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Tumeurs de l'appareil génital féminin , Tumeurs mammaires de l'animal , Animaux , Femelle , Lapins , Rats , Études rétrospectives , Cochons d'Inde , Tumeurs mammaires de l'animal/anatomopathologie , Tumeurs de l'appareil génital féminin/médecine vétérinaire , Tumeurs de l'appareil génital féminin/anatomopathologie , Souris , Mâle , Cricetinae , Furets , Animaux de compagnie , ChinchillaRÉSUMÉ
BACKGROUND: Thiostrepton (TST) is a known inhibitor of the transcription factor Forkhead box M1 (FoxM1) and inducer of heat shock response (HSR) and autophagy. TST thus may be one potential candidate of anticancer drugs for combination chemotherapy. METHODS AND RESULTS: Immunofluorescence staining of mitotic spindles and flow cytometry analysis revealed that TST induces mitotic spindle abnormalities, mitotic arrest, and apoptotic cell death in the MDA-MB-231 triple-negative breast cancer cell line. Interestingly, overexpression or depletion of FoxM1 in MDA-MB-231 cells did not affect TST induction of spindle abnormalities; however, TST-induced spindle defects were enhanced by inhibition of HSP70 or autophagy. Moreover, TST exhibited low affinity for tubulin and only slightly inhibited in vitro tubulin polymerization, but it severely impeded tubulin polymerization and destabilized microtubules in arrested mitotic MDA-MB-231 cells. Additionally, TST significantly enhanced Taxol cytotoxicity. TST also caused cytotoxicity and spindle abnormalities in a Taxol-resistant cell line, MDA-MB-231-T4R. CONCLUSIONS: These results suggest that, in addition to inhibiting FoxM1, TST may induce proteotoxicity and autophagy to disrupt cellular tubulin polymerization, and this mechanism might account for its antimitotic effects, enhancement of Taxol anticancer effects, and ability to overcome Taxol resistance in MDA-MB-231 cells. These data further imply that TST may be useful to improve the therapeutic efficacy of Taxol.
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Autophagie , Protéine M1 à motif en tête de fourche , Paclitaxel , Appareil du fuseau , Thiostrepton , Tubuline , Humains , Paclitaxel/pharmacologie , Thiostrepton/pharmacologie , Lignée cellulaire tumorale , Appareil du fuseau/effets des médicaments et des substances chimiques , Appareil du fuseau/métabolisme , Protéine M1 à motif en tête de fourche/métabolisme , Autophagie/effets des médicaments et des substances chimiques , Tubuline/métabolisme , Apoptose/effets des médicaments et des substances chimiques , Tumeurs du sein triple-négatives/traitement médicamenteux , Tumeurs du sein triple-négatives/métabolisme , Tumeurs du sein triple-négatives/anatomopathologie , Femelle , Synergie des médicaments , Microtubules/métabolisme , Microtubules/effets des médicaments et des substances chimiques , Mitose/effets des médicaments et des substances chimiques , Protéines du choc thermique HSP70/métabolisme , Cellules MDA-MB-231RÉSUMÉ
Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare subtype of renal cancer. The present report details the treatment experience of a case of MTSCC, where the patient underwent a right-side laparoscopic nephrectomy in October 2020 at Zhuji People's Hospital (Zhuji, China). A total of 3 months post-operation, multiple metastases were discovered in the right renal area and retroperitoneum, with rapid disease progression observed in the subsequent 2 months. Treatment with tislelizumab combined with pazopanib was ineffective, and the patient subsequently died. Although MTSCC is generally considered a low-grade 'indolent' tumor, with most patients achieving long-term survival post-surgery, a minority of cases, especially those of a higher grade, may experience postoperative recurrence and metastasis. Due to the rarity of metastatic MTSCC, most studies are based on small sample sizes or case reports, and there is a lack of standardized systemic treatment and follow-up strategies for metastatic MTSCC. The present paper summarizes and analyzes the clinical features, treatment methods and prognosis of metastatic MTSCC cases reported in the literature, aiming to provide assistance for the treatment and follow-up management of metastatic MTSCC. Even in cases of distant metastasis, aggressive surgical treatment, metastasectomy combined with molecular targeted or immunotherapy, may still be recommended.
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The spindle assembly checkpoint (SAC) temporally regulates mitosis by preventing progression from metaphase to anaphase until all chromosomes are correctly attached to the mitotic spindle. Centrosomes refine the spatial organization of the mitotic spindle at the spindle poles. However, centrosome loss leads to elongated mitosis, suggesting that centrosomes also inform the temporal organization of mitosis in mammalian cells. Here, we find that the mitotic delay in acentrosomal cells is enforced by the SAC in a MPS1-dependent manner, and that a SAC-dependent mitotic delay is required for bipolar cell division to occur in acentrosomal cells. Although acentrosomal cells become polyploid, polyploidy is not sufficient to cause dependency on a SAC-mediated delay to complete cell division. Rather, the division failure in absence of MPS1 activity results from mitotic exit occurring before acentrosomal spindles can become bipolar. Furthermore, prevention of centrosome separation suffices to make cell division reliant on a SAC-dependent mitotic delay. Thus, centrosomes and their definition of two spindle poles early in mitosis provide a 'timely two-ness' that allows cell division to occur in absence of a SAC-dependent mitotic delay.
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Protéines du cycle cellulaire , Centrosome , Points de contrôle de la phase M du cycle cellulaire , Mitose , Centrosome/métabolisme , Humains , Points de contrôle de la phase M du cycle cellulaire/physiologie , Protéines du cycle cellulaire/métabolisme , Protéines du cycle cellulaire/génétique , Protein-Serine-Threonine Kinases/métabolisme , Protein-Serine-Threonine Kinases/génétique , Appareil du fuseau/métabolisme , Appareil du fuseau/physiologie , Division cellulaire , Protein-tyrosine kinases/métabolisme , Protein-tyrosine kinases/génétique , Cellules HeLaRÉSUMÉ
INTRODUCTION AND IMPORTANCE: Mucinous Tubular and Spindle Cell Carcinoma (MTSCC) of the kidney is a rare variant, first classified by WHO in 2004 classification of RCC. MSCC has distinct morphology and immunohistochemistry unlike challenging previous renal tumor classifications. Despite its rarity, MTSCC diagnosis is important due to its unique characteristics. CASE PRESENTATION: We present a 56-year-old female with a decade-long history of right-side abdominal pain and swelling. Physical examination revealed a 15*10 cm mass on the right flank. Imaging indicated a heterogeneously enhancing right renal mass, diagnosed as localized right Renal Cell Carcinoma (RCC). A radical nephrectomy was performed, and the biopsy confirmed MTSCC. The patient was discharged on the 6th post-op day, with no adjuvant treatment due to localized tumors. CLINICAL DISCUSSION: MTSCC, constituting <1 % of RCC, primarily affects females (1:3-4) with an indolent course. Radical nephrectomy is the preferred treatment, offering a favorable prognosis. However, a small percentage may experience metastasis, necessitating mandatory follow-up. CONCLUSION: MTSCC of the kidney is a rare RCC variant with an excellent prognosis. Surgical excision, specifically radical nephrectomy, is the mainstay of treatment. Adjuvant therapy may not be required for localized tumors. Postoperative follow-up is crucial, despite the rare risk of metastasis reported in some cases.
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Fibrous dysplasia (FD) is a skeletal disorder characterized by the replacement of normal bone by fibrous tissue. Malignant transformation of FD is extremely rare and has been reported in both monostotic and polyostotic forms of FD. The most frequently reported malignant transformation is osteosarcoma. Among malignant bone tumors, spindle cell sarcomas are uncommon and difficult to diagnose. This report presents the case of a 30-year-old woman with an unusual presentation of a malignant undifferentiated spindle cell neoplasm secondary to fibrous dysplasia. The clinical features, radiological findings and management are discussed.
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Dysplasie fibreuse des os , Sarcomes , Humains , Femelle , Adulte , Sarcomes/anatomopathologie , Sarcomes/imagerie diagnostique , Sarcomes/diagnostic , Dysplasie fibreuse des os/anatomopathologie , Dysplasie fibreuse des os/diagnostic , Dysplasie fibreuse des os/imagerie diagnostique , Tumeurs osseuses/anatomopathologie , Tumeurs osseuses/diagnostic , Tumeurs osseuses/imagerie diagnostique , Diagnostic différentiel , Transformation cellulaire néoplasique/anatomopathologieRÉSUMÉ
Background: Myotonic dystrophy type 1 (DM1) is a rare multisystemic genetic disorder with motor hallmarks of myotonia, muscle weakness and wasting. DM1 patients have an increased risk of falling of multifactorial origin, and proprioceptive and vestibular deficits can contribute to this risk. Abnormalities of muscle spindles in DM1 have been known for years. This observational cross-sectional study was based on the hypothesis of impaired cervical proprioception caused by alterations in the neck spindles. Methods: Head position sense was measured in 16 DM1 patients and 16 age- and gender-matched controls. A head-to-target repositioning test was requested from blindfolded participants. Their head was passively rotated approximately 30° leftward or rightward and flexed or extended approximately 25°. Participants had to replicate the imposed positions. An optoelectronic system was adopted to measure the angular differences between the reproduced and the imposed positions (joint position error, JPE, °) concerning the intended (sagittal, horizontal) and unintended (including the frontal) planar projections. In DM1 patients, JPEs were correlated with clinical and balance measures. Static balance in DM1 patients was assessed through dynamic posturography. Results: The accuracy and precision of head repositioning in the intended sagittal and horizontal error components did not differ between DM1 and controls. On the contrary, DM1 patients showed unintended side-bending to the left and the right: the mean [95%CI] of frontal JPE was -1.29° [-1.99°, -0.60°] for left rotation and 0.98° [0.28°, 1.67°] for right rotation. The frontal JPE of controls did not differ significantly from 0° (left rotation: 0.17° [-0.53°, 0.87°]; right rotation: -0.22° [-0.91°, 0.48°]). Frontal JPE differed between left and right rotation trials (p < 0.001) only in DM1 patients. No correlation was found between JPEs and measures from dynamic posturography and clinical scales. Conclusions: Lateral head bending associated with head rotation may reflect a latent impairment of neck proprioception in DM1 patients.
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To ensure an even segregation of chromosomes during somatic cell division, eukaryotes rely on mitotic spindles. Here, we measured prime characteristics of the Arabidopsis mitotic spindle and built a three-dimensional dynamic model using Cytosim. We identified the cell-cycle regulator CYCLIN-DEPENDENT KINASE B1 (CDKB1) together with its cyclin partner CYCB3;1 as key regulators of spindle morphology in Arabidopsis. We found that the augmin component ENDOSPERM DEFECTIVE1 (EDE1) is a substrate of the CDKB1;1-CYCB3;1 complex. A non-phosphorylatable mutant rescue of ede1 resembled the spindle phenotypes of cycb3;1 and cdkb1 mutants and the protein associated less efficiently with spindle microtubules. Accordingly, reducing the level of augmin in simulations recapitulated the phenotypes observed in the mutants. Our findings emphasize the importance of cell-cycle-dependent phospho-control of the mitotic spindle in plant cells and support the validity of our model as a framework for the exploration of mechanisms controlling the organization of the eukaryotic spindle.
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The acentrosomal spindle apparatus has kinetochore fibers organized and converged toward opposite poles; however, mechanisms underlying the organization of these microtubule fibers into an orchestrated bipolar array were largely unknown. Kinesin-14D is one of the four classes of Kinesin-14 motors that are conserved from green algae to flowering plants. In Arabidopsis thaliana, three Kinesin-14D members displayed distinct cell cycle-dependent localization patterns on spindle microtubules in mitosis. Notably, Kinesin-14D1 was enriched on the midzone microtubules of prophase and mitotic spindles and later persisted in the spindle and phragmoplast midzones. The kinesin-14d1 mutant had kinetochore fibers disengaged from each other during mitosis and exhibited hypersensitivity to the microtubule-depolymerizing herbicide oryzalin. Oryzalin-treated kinesin-14d1 mutant cells had kinetochore fibers tangled together in collapsed spindle microtubule arrays. Kinesin-14D1, unlike other Kinesin-14 motors, showed slow microtubule plus end-directed motility, and its localization and function were dependent on its motor activity and the novel malectin-like domain. Our findings revealed a Kinesin-14D1-dependent mechanism that employs interpolar microtubules to regulate the organization of kinetochore fibers for acentrosomal spindle morphogenesis.
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Protéines d'Arabidopsis , Arabidopsis , Kinésine , Microtubules , Appareil du fuseau , Arabidopsis/métabolisme , Arabidopsis/génétique , Kinésine/métabolisme , Kinésine/génétique , Microtubules/métabolisme , Protéines d'Arabidopsis/métabolisme , Protéines d'Arabidopsis/génétique , Appareil du fuseau/métabolisme , Mitose , Morphogenèse , Kinétochores/métabolisme , Dinitrobenzènes/pharmacologie , Sulfamides/pharmacologieRÉSUMÉ
Proprioception plays a crucial role in motor coordination and self-perception. Muscle spindles are the principal receptors for proprioception. They are believed to encode muscle stretch and signal limb position and velocity. Here, we applied percutaneous pressure to a small area of extensor muscles at the forearm while recording spindle afferent responses, skeletal muscle activity, and hand kinematics. Three levels of sustained pressure were applied on the spindle-bearing muscle when the hand was relaxed and immobile ("isometric" condition) and when the participant's hand moved rhythmically at the wrist. As hypothesized to occur due to compression of the spindle capsule, we show that muscle pressure is an "adequate" stimulus for human spindles in isometric conditions and that pressure enhances spindle responses during stretch. Interestingly, release of sustained pressure in isometric conditions lowered spindle firing below baseline rates. Our findings urge a re-evaluation of muscle proprioception in sensorimotor function and various neuromuscular pathologies.
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Background: The widespread use of radiofrequency (RF) sources, ranging from household appliances to telecommunications devices and military equipment, raises concerns among people and regulatory agencies about the potential health risks of RF exposure. Consequently, several in vitro and in vivo studies have been done to investigate the biological effects, in particular non-thermal, of this non-ionizing radiation. To date, this issue is still being debated due to the controversial results that have been reported. Furthermore, the impact of different RF signal modulations on biological systems remains poorly investigated. The present in vitro study aims to evaluate the cytotoxicity and genotoxicity of continuous or pulsed 1.6 GHz RF in human dermal fibroblasts (HDF). Methods: HDF cultures were exposed to continuous and pulsed 1.6 GHz RF, for 2 h, with Specific Absorption Rate (SAR) of 0.4 W/kg. The potential biological effects of 1.6 GHz RF on HDF were assessed with a multi-methodological approach, analyzing the effects on cell cycle, ultrastructure, protein expression, mitotic spindle, CREST stained micronuclei, chromosome segregation and γ-H2AX/53BP1 foci. Results: 1.6 GHz RF exposure modified proteins expression and morphology of HDF. Specifically, the expression of different heat-shock proteins (HSP) (i.e., HSP-90, HSP-60, and HSP-25) and phospho-AKT were affected. In addition, both continuous and pulsed RF modified the cytoskeletal organization in HDF and increased the number of lysosomes, while the formation of autophagosomes was observed only after pulsed RF exposure. Mitotic spindle anomalies were also found after exposure. However, no significant effect was observed on cell cycle, chromosome segregation, CREST-stained micronuclei and γ-H2AX/53BP1 foci. Conclusion: The results of the present study show the absence of genotoxic damage in 1.6 GHz RF exposed HDF and, although mitotic spindle alterations were observed, they did not have an aneugenic effect. On the other hand, changes in some proteins expression and cell ultrastructure in exposed HDF suggest that RF can potentially induce cell alterations at the morphological and molecular levels.
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Fibroblastes , Ondes hertziennes , Humains , Fibroblastes/effets des radiations , Ondes hertziennes/effets indésirables , Altération de l'ADN , Cycle cellulaire/effets des radiations , Cellules cultivéesRÉSUMÉ
Bis(2-ethylhexyl) phthalate is the most abundant phthalate used as plasticizer to soften plastics and polymers included in medical devices. Human and environmental exposure may occur because DEHP is not chemically bound to plastics and can easily leach out of the materials. This phthalate is classified as reproductive toxicant and possible carcinogen to humans. The genotoxic potential has still to be clarified, but there are indications suggesting that DEHP may have aneugenic effects. To further investigate DEHP genotoxicity, the cytochalasin-block micronucleus assay was applied and combined with the CREST staining to characterise micronucleus content and gain insights on its genotoxic mode of action. Chromosomal damage was also analysed in metaphase and ana-telophase cells and the morphology of the mitotic spindle was investigated to evaluate the possible involvement of this cellular apparatus as a target of DEHP. Our findings indicated that DEHP induced a statistically significant increase in the frequency of micronuclei as well as in the frequency of CREST-positive micronuclei. Consistently, disturbance of chromosome segregation and induction of numerical chromosome changes were observed together with changes in spindle morphology, formation of multipolar spindles and alteration of the microtubule network. Experiments performed without metabolic activation demonstrated a direct action of DEHP on chromosome segregation not mediated by its metabolites. In conclusion, there is consistent evidence for an aneugenic activity of DEHP. A thresholded genotoxic activity was identified for DEHP, disclosing possible implications for risk assessment.
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Aneugènes , Phtalate de bis[2-éthylhexyle] , Tests de micronucleus , Appareil du fuseau , Tests de micronucleus/méthodes , Appareil du fuseau/effets des médicaments et des substances chimiques , Phtalate de bis[2-éthylhexyle]/toxicité , Aneugènes/toxicité , Humains , Plastifiants/toxicité , Aberrations des chromosomes/induit chimiquement , Aberrations des chromosomes/effets des médicaments et des substances chimiques , Micronoyaux à chromosomes défectueux/induit chimiquement , Micronoyaux à chromosomes défectueux/effets des médicaments et des substances chimiques , Animaux , Cytochalasine B/pharmacologie , Ségrégation des chromosomes/effets des médicaments et des substances chimiquesRÉSUMÉ
BACKGROUND: Monopolar spindle-binding protein 3B (MOB3B) functions as a signal transducer and altered MOB3B expression is associated with the development of human cancers. AIM: To investigate the role of MOB3B in colorectal cancer (CRC). METHODS: This study collected 102 CRC tissue samples for immunohistochemical detection of MOB3B expression for association with CRC prognosis. After overexpression and knockdown of MOB3B expression were induced in CRC cell lines, changes in cell viability, migration, invasion, and gene expression were assayed. Tumor cell autophagy was detected using transmission electron microscopy, while nude mouse xenograft experiments were performed to confirm the in-vitro results. RESULTS: MOB3B expression was reduced in CRC vs normal tissues and loss of MOB3B expression was associated with poor CRC prognosis. Overexpression of MOB3B protein in vitro attenuated the cell viability as well as the migration and invasion capacities of CRC cells, whereas knockdown of MOB3B expression had the opposite effects in CRC cells. At the molecular level, microtubule-associated protein light chain 3 II/I expression was elevated, whereas the expression of matrix metalloproteinase (MMP)2, MMP9, sequestosome 1, and phosphorylated mechanistic target of rapamycin kinase (mTOR) was downregulated in MOB3B-overexpressing RKO cells. In contrast, the opposite results were observed in tumor cells with MOB3B knockdown. The nude mouse data confirmed these in-vitro findings, i.e., MOB3B expression suppressed CRC cell xenograft growth, whereas knockdown of MOB3B expression promoted the growth of CRC cell xenografts. CONCLUSION: Loss of MOB3B expression promotes CRC development and malignant behaviors, suggesting a potential tumor suppressive role of MOB3B in CRC by inhibition of mTOR/autophagy signaling.
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Autophagie , Mouvement cellulaire , Tumeurs colorectales , Invasion tumorale , Transduction du signal , Sérine-thréonine kinases TOR , Sujet âgé , Animaux , Femelle , Humains , Mâle , Souris , Adulte d'âge moyen , Protéines adaptatrices de la transduction du signal/métabolisme , Protéines adaptatrices de la transduction du signal/génétique , Lignée cellulaire tumorale , Survie cellulaire , Tumeurs colorectales/anatomopathologie , Tumeurs colorectales/métabolisme , Tumeurs colorectales/génétique , Régulation négative , Régulation de l'expression des gènes tumoraux , Techniques de knock-down de gènes , Souris de lignée BALB C , Souris nude , Pronostic , Sérine-thréonine kinases TOR/métabolismeRÉSUMÉ
Spindle epithelial tumor with thymus-like elements (SETTLE) is a rare malignant neoplasm of the thyroid gland which is believed to arise from intrathyroidal thymic tissue. It predominantly affects young adults and children presenting with a thyroid mass of variable duration and rarely occurs in adults. It has a high overall survival with a tendency for delayed metastasis. SETTLE is a biphasic lobulated tumor composed of spindle shaped cells along with glandular formations seen on histopathological examination. Despite its typical morphology it is commonly misdiagnosed on histopathology due to its rarity and overlapping morphology with other close mimics such as a carcinoma, synovial sarcoma and thymoma. Herein we report such a case occurring in a middle aged female presenting with a neck mass. She had an initial diagnosis of metastatic poorly differentiated squamous cell carcinoma possibly with an orophayngeal primary in view of co expression of CK, p40 and p16 on immunohistochemistry. The patient underwent surgical resection with modified neck dissection. On review at our hospital it was diagnosed as SETTLE and she remains disease free after a follow-up period of 1 year. Diligent histopathological examination espoused with a judicious panel of IHC markers in conjunction with clinicoradiological findings forms the mainstay of diagnosis. Diffuse and strong p16 immunoexpression has not been documented or evaluated in literature so far, and needs to be explored for its diagnostic utility in this rare entity.
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Marqueurs biologiques tumoraux , Humains , Femelle , Marqueurs biologiques tumoraux/analyse , Adulte d'âge moyen , Tumeurs de la thyroïde/anatomopathologie , Tumeurs de la thyroïde/diagnostic , Immunohistochimie , Diagnostic différentiel , Tumeurs du thymus/anatomopathologie , Tumeurs du thymus/diagnostic , Évidement ganglionnaire cervical , Tumeurs épithéliales épidermoïdes et glandulaires/anatomopathologie , Tumeurs épithéliales épidermoïdes et glandulaires/diagnostic , Carcinome épidermoïde/anatomopathologie , Carcinome épidermoïde/diagnosticRÉSUMÉ
Fibromyxomatous spindle cell neoplasms are an unusual form of dysplasia. It is extremely rare in the nose and paranasal sinuses. We present a 60 year lady with swelling over the dorsum of nose and nasal block for 4 years. She underwent combined approach excision of mass. Histopathology revealed fibromyxomatous spindle cell tumour.