-
Birth Defects Research. Part C, Embryo... Jun 2007Retinoic acid (RA) is a signaling molecule synthesized from vitamin A that controls gene expression at the transcriptional level by functioning as a ligand for nuclear... (Review)
Review
Retinoic acid (RA) is a signaling molecule synthesized from vitamin A that controls gene expression at the transcriptional level by functioning as a ligand for nuclear RA receptors. RA plays an essential role during embryonic development in higher animals by regulating key genes involved in pattern formation. RA is required for induction of several Hox genes involved in patterning of the hindbrain and spinal cord as neuroectoderm emerges from the primitive streak. Recent findings indicate that RA is also required to ensure bilaterally symmetrical generation of left and right somites as presomitic mesoderm emerges from the primitive streak. RA may control somitogenesis through its ability to repress posterior ectodermal expression of fibroblast growth factor-8 (Fgf8) for a short period of time during the late primitive streak stage when the somitogenesis clock initiates. During this tight temporal window, RA is required to limit Fgf8 expression to the most posterior ectoderm (epiblast), thus preventing ectopic Fgf8 expression in more anterior ectoderm including the node ectoderm and neuroectoderm. Although Fgf8 is required for the node to impart left-right asymmetry on specific tissues (heart, visceral organs, etc.), excess Fgf8 signaling following a loss of RA may stimulate the node to generate asymmetry also in presomitic mesoderm, leading to left-right asymmetry in the somitogenesis clock. These findings suggest that human vertebral birth defects such as scoliosis, an abnormal left-right bending of the vertebral column, may be caused by a defect in RA signaling during somitogenesis.
Topics: Animals; Biological Clocks; Body Patterning; Congenital Abnormalities; Embryonic Development; Female; Fibroblast Growth Factor 8; Gene Expression Regulation, Developmental; Humans; Pregnancy; Receptors, Retinoic Acid; Somites; Tretinoin; Vitamin A
PubMed: 17600781
DOI: 10.1002/bdrc.20092 -
World Journal of Methodology Dec 2015The transcription factor forkhead box protein A2 (FOXA2, also known as hepatocyte nuclear factor 3β or transcription factor 3β), has been found to play pivotal roles... (Review)
Review
The transcription factor forkhead box protein A2 (FOXA2, also known as hepatocyte nuclear factor 3β or transcription factor 3β), has been found to play pivotal roles in multiple phases of mammalian life, from the early development to the organofaction, and subsequently in homeostasis and metabolism in the adult. In the embryonic development period, FOXA2 is require d for the formation of the primitive node and notochord, and its absence results in embryonic lethality. Moreover, FOXA2 plays an important role not only in lung development, but also in T helper type 2 (Th2)-mediated pulmonary inflammation and goblet cell hyperplasia. In this article, the role of FOXA2 in lung development and Th2-mediated pulmonary inflammation, as well as in goblet cell hyperplasia, is reviewed. FOXA2 deletion in airway epithelium results into Th2-mediated pulmonary inflammation and goblet cell hyperplasia in developing lung. Leukotriene pathway and signal transducers and activators of transcription 6 pathway may mediate this inflammation through recruitment and activation of denditric cell during lung developments. FOXA2 is a potential treatment target for lung diseases with Th2 inflammation and goblet cell hyperplasia, such as asthma and chronic obstructive pulmonary disease.
PubMed: 26713283
DOI: 10.5662/wjm.v5.i4.223 -
Developmental Dynamics : An Official... Apr 2020Hensen node of the amniote embryo plays a central role in multiple developmental processes, especially in induction and formation of axial organs. In the chick, it is...
BACKGROUND
Hensen node of the amniote embryo plays a central role in multiple developmental processes, especially in induction and formation of axial organs. In the chick, it is asymmetrical in shape and has recently been considered to represent the left-right organizer. As mechanisms of breaking the initial left-right symmetry of the embryo are still ill-understood, analyzing the node's microarchitecture may provide insights into functional links between symmetry breaking and asymmetric morphology.
RESULTS
In the course of a light- and electron-microscopic study addressing this issue we discovered novel intercellular matrix-filled cavities in the node of the chick during gastrulation and during early neurulation stages; measuring up to 45 μm, they are surrounded by densely packed cells and filled with nanoscale fibrils, which immunostaining suggests to consist of the basement membrane-related proteins fibronectin and perlecan. The cavities emerge immediately prior to node formation in the epiblast layer adjacent to the tip of the primitive streak and later, with emerging node asymmetry, they are predominantly located in the right part of the node. Almost identical morphological features of microcavities were found in the duck node.
CONCLUSIONS
We address these cavities as "nodal microcavities" and propose their content to be involved in the function of the avian node by mediating morphogen signaling and storage.
Topics: Animals; Basement Membrane; Chickens; Ducks; Fibronectins; Gastrulation; Heparan Sulfate Proteoglycans; Microscopy, Electron; Organizers, Embryonic
PubMed: 31729123
DOI: 10.1002/dvdy.133 -
Disease Markers 2015HER2 expression in gastric cancer (GC) has received attention as a potential target for therapy with Trastuzumab. We reviewed the current knowledge on HER2 status in... (Review)
Review
OBJECTIVES
HER2 expression in gastric cancer (GC) has received attention as a potential target for therapy with Trastuzumab. We reviewed the current knowledge on HER2 status in premalignant gastric lesions and in early (EGC) and advanced (AGC) GC to discuss the possible pathogenetic and prognostic roles of HER2 overexpression in GC.
RESULTS
HER2 overexpression was documented in gastric low-grade (LG) and high-grade intraepithelial neoplasia (HG-IEN), with higher frequency in gastric type dysplasia. HER2 overexpression was significantly associated with disease recurrence and poor prognosis in EGC representing an independent risk factor for lymph node metastases. HER2 overexpression was more frequent in AGC characterized by high grade, advanced stage, and high Ki-67 labeling index. The discordance in HER2 status was evidenced between primitive GC and synchronous or metachronous metastases.
CONCLUSIONS
HER2 overexpression in premalignant gastric lesions suggests its potential involvement in the early steps of gastric carcinogenesis. The assessment of HER2 status in EGC may be helpful for the identification of patients who are at low risk for developing nodal metastases. Finally, the possible discordance in HER2 status between primary GC and its synchronous metastases support routine assessment of HER2 both in the primary GC and in its metastatic lesions.
Topics: Biomarkers, Tumor; Humans; Lymphatic Metastasis; Receptor, ErbB-2; Stomach Neoplasms
PubMed: 26494937
DOI: 10.1155/2015/234851 -
Developmental Dynamics : An Official... May 2016The notochord is a structure common to all chordates, and the feature that the phylum Chordata has been named after. It is a rod-like mesodermal structure that runs the... (Review)
Review
The notochord is a structure common to all chordates, and the feature that the phylum Chordata has been named after. It is a rod-like mesodermal structure that runs the anterior-posterior length of the embryo, adjacent to the ventral neural tube. The notochord plays a critical role in embryonic tissue patterning, for example the dorsal-ventral patterning of the neural tube. The cells that will come to form the notochord are specified at gastrulation. Axial mesodermal cells arising at the anterior primitive streak migrate anteriorly as the precursors of the notochord and populate the notochordal plate. Yet, even though a lot of interest has centered on investigating the functional and structural roles of the notochord, we still have a very rudimentary understanding of notochord morphogenesis. The events driving the formation of the notochord are rapid, taking place over the period of approximately a day in mice. In this commentary, we provide an overview of our current understanding of mouse notochord morphogenesis, from the initial specification of axial mesendodermal cells at the primitive streak, the emergence of these cells at the midline on the surface of the embryo, to their submergence and organization of the stereotypically positioned notochord. We will also discuss some key open questions. Developmental Dynamics 245:547-557, 2016. © 2016 Wiley Periodicals, Inc.
Topics: Animals; Mesoderm; Mice; Morphogenesis; Notochord; Primitive Streak
PubMed: 26845388
DOI: 10.1002/dvdy.24392 -
Journal of Visualized Surgery 2018The incidental detection of solitary pulmonary nodule (SPN) is currently increasing due to the widespread use of computed tomography (CT) during the follow up in...
BACKGROUND
The incidental detection of solitary pulmonary nodule (SPN) is currently increasing due to the widespread use of computed tomography (CT) during the follow up in oncological patients or in screening trials. A quick and definitive histological diagnosis of these nodes is mandatory as, in case of primitive lung cancer, an early detection could improve both surgical results and prognosis. The minimally invasive pulmonary resection (MIPR) is the gold standard procedure for diagnosis and treatment of small lung nodules, but it can be difficult to localize deep nonpalpable nodes that lie in the lung parenchyma. Hence, throughout the years several techniques have been developed to better localize deep or sub solid nodes. We describe our experience with radio-guided technique.
METHODS
Patients with SPN smaller than 10 mm and/or with a distance from the visceral pleura equal or larger than 10 mm underwent MIPR after CT injection of a solution containing 0.2 mL Tc-labelled human serum albumin microspheres and 0.1 mL of non-ionic contrast. During surgical procedures, a collimated probe, connected to a gamma-ray detector, was used to scan the lung and detect the target area. The area of major radioactivity was then resected.
RESULTS
Between 2010 and 2015, 175 patients (M/F: 97/78) underwent minimally invasive resection (thoracoscopic or robotic) with radio-guided technique. The mean node diameter was 13 mm (range, 5-20 mm), and the mean distance from the visceral pleura was 15 mm (range, 6-39 mm). No significant CT-guided-injection-related complications occurred, except for 13 patients (7.4%) who developed a pneumothorax (PNX) not requiring chest tube insertion. This technique guaranteed a successfully intra-operative node localization in 100% of cases. The mean duration of the surgical procedure was 44 min (range, 25-130 min). The mean length of pleural drainage and mean hospital stay was 2.6 days (range, 1-5 days) and 3.9 days (range, 1-7 days) respectively. No mortality or perioperative complications occurred. Pathology reports showed 105 metastases, 55 primitive lung cancers and 15 benign lesions. In case of suspicion of primitive lung tumour an intraoperative frozen exam was conducted, and all patients underwent lobectomy or segmentectomy with lymphadenectomy [41 patients with thoracotomy, 11 with robotic surgery and 3 with video-assisted thoracoscopic surgery (VATS)].
CONCLUSIONS
Our experience confirms that radio-guided thoracoscopic surgery (RGTS) is a feasible and safe procedure, thanks to its high success rate the radio-guided technique is helpful to overcome the lack of tactile feedback during MIPR [VATS and robotic-assisted thoracoscopic surgery (RATS)] and to limit conversion to open surgery.
PubMed: 29552518
DOI: 10.21037/jovs.2018.01.19 -
Journal of Pharmacy & Bioallied Sciences Jul 2023Premetastatic niche (PMN) concept, introduced by David Lyden and colleagues, is an area that can support cancer cells to nurture in it, but the area itself being bereft... (Review)
Review
Premetastatic niche (PMN) concept, introduced by David Lyden and colleagues, is an area that can support cancer cells to nurture in it, but the area itself being bereft of cancerous cells. It provides a microenvironment that is congenial for tumor invasion, endurance, and or proliferation of malignant cells to develop into metastasis. These are noncancerous variations in a tumor-free organ and are the most primitive indications of metastasis. These may have a potential to serve as a diagnostic aid, prognostic biomarkers, and therapeutic target. Nevertheless, there is still no clear elucidation on diverse trails of tumor metastasis via lymphatic or hematogenous route, especially in relationship with the PMN. In this review, contemporary knowledge associated with nodal premetastatic niche formation with forthcoming directions on translational and clinical research is deliberated.
PubMed: 37654347
DOI: 10.4103/jpbs.jpbs_49_23 -
Interactive Cardiovascular and Thoracic... Jan 2022Lung metastases from gynaecological tract cancers are rare, and prognostic factors are still undefined. The goal of this study was to analyse prognostic factors for...
OBJECTIVES
Lung metastases from gynaecological tract cancers are rare, and prognostic factors are still undefined. The goal of this study was to analyse prognostic factors for survival in this group of patients.
METHODS
Data of patients with lung metastases from gynaecological tract cancers who underwent surgical resections from 1 January 2005 to 31 May 2019 were reviewed retrospectively. All patients were treated surgically if the primitive tumour was under control and the lung was the only organ involved. Clinical and pathological data associated with metastatic patterns and previous treatment types were correlated with overall survival (OS) and disease-free survival using Kaplan-Meier curves, whereas the log-rank test was used to assess differences between subgroups.
RESULTS
The analysis was conducted on 55 patients. OS was 65% at 5 years. With univariable analysis, age >45 years (P = 0.022) and the absence of pleural infiltration (P = 0.001) were determined to be favourable prognostic factors. The 5-year OS was 69.9% versus 53.3% in patients with pleural involvement. Multivariable analysis confirmed the absence of pleural infiltration as a favourable independent prognostic factor; the hazard ratio was 0.06; the 95% confidence interval was 0.00-0.23 (P = 0.011).At univariable analysis, the absence of pleural infiltration was determined to be a favourable prognostic factor (P = 0.034) for disease-free survival. The numbers and dimensions of the metastases did not influence survival in these patients.In uterine cancers of endometrial or cervical origin, the presence of pleural infiltration (P = 0.001), lymph node involvement (P = 0.001) and young age (P = 0.044) were considered unfavourable prognostic factors for OS.
CONCLUSIONS
Surgical treatment in technically resectable gynaecological tract metastases may represent an important option. Pleural infiltration and lymph node metastases seem to be adverse prognostic factors.
Topics: Humans; Lung Neoplasms; Lymph Nodes; Middle Aged; Prognosis; Retrospective Studies; Survival Rate
PubMed: 34999792
DOI: 10.1093/icvts/ivab216 -
NeuroImage. Clinical 2018To evaluate functional connectivity (FC) in patients with sleep-related hypermotor epilepsy (SHE) compared to healthy controls.
OBJECTIVES
To evaluate functional connectivity (FC) in patients with sleep-related hypermotor epilepsy (SHE) compared to healthy controls.
METHODS
Resting state fMRI was performed in 13 patients with a clinical diagnosis of SHE (age = 38.3 ± 11.8 years, 6 M) and 13 matched healthy controls (age = 38.5 ± 10.8 years, 6 M).Data were first analysed using probabilistic independent component analysis (ICA), then a graph theoretical approach was applied to assess topological and organizational properties at the whole brain level. We evaluated node degree (ND), betweenness centrality (BC), clustering coefficient (CC), local efficiency (LE) and global efficiency (GE). The differences between the two groups were evaluated non-parametrically.
RESULTS
At the group level, we distinguished 16 RSNs (Resting State Networks). Patients showed a significantly higher FC in sensorimotor and thalamic regions ( < 0.05 corrected). Compared to controls, SHE patients showed no significant differences in network global efficiency, while ND and BC were higher in regions of the limbic system and lower in the occipital cortex, while CC and LE were higher in regions of basal ganglia and lower in limbic areas ( < 0.05 uncorrected).
DISCUSSION AND CONCLUSIONS
The higher FC of the sensorimotor cortex and thalamus might be in agreement with the hypothesis of a peculiar excitability of the motor cortex during thalamic K-complexes. This sensorimotor-thalamic hyperconnection might be regarded as a consequence of an alteration of the arousal regulatory system in SHE. An altered topology has been found in structures like basal ganglia and limbic system, hypothesized to be involved in the pathophysiology of the disease as suggested by the dystonic-dyskinetic features and primitive behaviours observed during the seizures.
Topics: Adolescent; Adult; Brain; Epilepsy; Female; Humans; Hyperkinesis; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Neural Pathways; Oxygen; Sleep; Statistics, Nonparametric; Young Adult
PubMed: 29527492
DOI: 10.1016/j.nicl.2017.12.002 -
SAGE Open Medical Case Reports 2023Mucosal melanoma is a rare subtype of melanoma distinct from the cutaneous type in its clinical and biological aspects, requiring different therapeutical management....
Mucosal melanoma is a rare subtype of melanoma distinct from the cutaneous type in its clinical and biological aspects, requiring different therapeutical management. Anorectal melanomas represent less than 1% of anorectal cancers and 0.3% of malignant melanomas, and they are by far the most studied type. Proctologic examination, colonoscopy, and biopsy can establish a correct diagnosis. Imaging techniques, especially MRI can show some characteristic features, but it is essentially performed for extension assessment. We report the case of a 63-year-old man who consulted for rectal bleeding. The proctological examination found a brownish ulcerative-vegetating tumor of 3 cm in diameter located 3 cm from the anal rim. The endoscopic examination revealed a predominance of ulcerative budding lesions and the biopsy specimen confirmed a rectal melanoma. The extension assessment, based on a computed tomography scan and MRI did not show locoregional or distant metastases. Radiotherapy and abdominoperineal resection with pelvic node dissection was the treatment of choice with good evolution.
PubMed: 37654557
DOI: 10.1177/2050313X231194150