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ELife Mar 2023During early vertebrate development, signals from a special region of the embryo, the organizer, can redirect the fate of non-neural ectoderm cells to form a complete,...
During early vertebrate development, signals from a special region of the embryo, the organizer, can redirect the fate of non-neural ectoderm cells to form a complete, patterned nervous system. This is called neural induction and has generally been imagined as a single signalling event, causing a switch of fate. Here, we undertake a comprehensive analysis, in very fine time course, of the events following exposure of competent ectoderm of the chick to the organizer (the tip of the primitive streak, Hensen's node). Using transcriptomics and epigenomics we generate a gene regulatory network comprising 175 transcriptional regulators and 5614 predicted interactions between them, with fine temporal dynamics from initial exposure to the signals to expression of mature neural plate markers. Using in situ hybridization, single-cell RNA-sequencing, and reporter assays, we show that the gene regulatory hierarchy of responses to a grafted organizer closely resembles the events of normal neural plate development. The study is accompanied by an extensive resource, including information about conservation of the predicted enhancers in other vertebrates.
Topics: Animals; Gene Regulatory Networks; Nervous System; Chickens; Embryonic Development; Organizers, Embryonic; Vertebrates
PubMed: 36867045
DOI: 10.7554/eLife.73189 -
Annals of Surgery Sep 2022The role of parenchyma-sparing resections (PSR) and lymph node dissection in small (<3 cm) nonfunctional pancreatic neuroendocrine tumors (PNET) is unlikely to be... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
The role of parenchyma-sparing resections (PSR) and lymph node dissection in small (<3 cm) nonfunctional pancreatic neuroendocrine tumors (PNET) is unlikely to be studied in a prospective randomized clinical trial. By combining data from 4 high-volume pancreatic centers we compared postoperative and long-term outcomes of patients who underwent PSR with patients who underwent oncologic resections.
METHODS
Retrospective review of prospectively collected clinicopathologic data of patients who underwent pancreatectomy between 2000 and 2021 was collected from 4 high-volume institutions. PSR and lymph node-sparing resections (enucleation and central pancreatectomy) were compared to those who underwent oncologic resections with lymphadenectomy (pancreaticoduodenectomy, distal pancreatectomy). Statistical testing was performed using χ 2 test and t test, survival estimates with Kaplan-Meier method and multivariate analysis using Cox proportional hazard model.
RESULTS
Of 810 patients with small sporadic nonfunctional PNETs, 121 (14.9%) had enucleations, 100 (12.3%) had central pancreatectomies, and 589 (72.7%) patients underwent oncologic resections. The median age was 59 years and 48.2% were female with a median tumor size of 2.5 cm. After case-control matching for tumor size, 221 patients were selected in each group. Patients with PSR were more likely to undergo minimally invasive operations (32.6% vs 13.6%, P <0.001), had less intraoperative blood loss (358 vs 511 ml, P <0.001) and had shorter operative times (180 vs 330 minutes, P <0.001) than patients undergoing oncologic resections. While the mean number of lymph nodes harvested was lower for PSR (n=1.4 vs n=9.9, P <0.001), the mean number of positive lymph nodes was equivalent to oncologic resections (n=1.1 vs n=0.9, P =0.808). Although the rate of all postoperative complications was similar for PSR and oncologic resections (38.5% vs 48.2%, P =0.090), it was higher for central pancreatectomies (38.5% vs 56.6%, P =0.003). Long-term median disease-free survival (190.5 vs 195.2 months, P =0.506) and overall survival (197.9 vs 192.6 months, P =0.372) were comparable. Of the 810 patients 136 (16.7%) had no lymph nodes resected. These patients experienced less blood loss, shorter operations ( P <0.001), and lower postoperative complication rates as compared to patients who had lymphadenectomies (39.7% vs 56.9%, P =0.008). Median disease-free survival (197.1 vs 191.9 months, P =0.837) and overall survival (200 vs 195.1 months, P =0.827) were similar for patients with no lymph nodes resected and patients with negative lymph nodes (N0) after lymphadenectomy.
CONCLUSION
In small <3 cm nonfunctional PNETs, PSRs and lymph node-sparing resections are associated with lower blood loss, shorter operative times, and lower complication rates when compared to oncologic resections, and have similar long-term oncologic outcomes.
Topics: Female; Humans; Male; Middle Aged; Neuroectodermal Tumors, Primitive; Neuroendocrine Tumors; Pancreatectomy; Pancreatic Neoplasms; Prospective Studies; Retrospective Studies; Treatment Outcome
PubMed: 35758433
DOI: 10.1097/SLA.0000000000005559 -
Proceedings of the National Academy of... Feb 2022In warm-blooded vertebrate embryos (mammals and birds), the axial tissues of the body form from a growth zone at the tail end, Hensen's node, which generates neural,...
In warm-blooded vertebrate embryos (mammals and birds), the axial tissues of the body form from a growth zone at the tail end, Hensen's node, which generates neural, mesodermal, and endodermal structures along the midline. While most cells only pass through this region, the node has been suggested to contain a small population of resident stem cells. However, it is unknown whether the rest of the node constitutes an instructive niche that specifies this self-renewal behavior. Here, we use heterotopic transplantation of groups and single cells and show that cells not destined to enter the node can become resident and self-renew. Long-term resident cells are restricted to the posterior part of the node and single-cell RNA-sequencing reveals that the majority of these resident cells preferentially express G2/M phase cell-cycle-related genes. These results provide strong evidence that the node functions as a niche to maintain self-renewal of axial progenitors.
Topics: Animals; Body Patterning; Chick Embryo; Endoderm; Gastrula; Mesoderm; Nervous System; Notochord; Organizers, Embryonic; Stem Cell Niche; Stem Cells
PubMed: 35101917
DOI: 10.1073/pnas.2108935119 -
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 -
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 -
World Journal of Surgical Oncology Aug 2020Pancreatic neuroendocrine tumors (PNET) are rare, with a significant malignant potential. This study aimed to determine outcomes of patients with resected PNETs...
BACKGROUND
Pancreatic neuroendocrine tumors (PNET) are rare, with a significant malignant potential. This study aimed to determine outcomes of patients with resected PNETs according to the cystic component and confirm the accuracy of preoperative staging.
METHODS
From 1997 to 2016, 106 patients underwent resection of PNETs, including 73 purely solid (S-PNETs, 69%), 21 mixed (M-PNETs, 20%), and 12 purely cystic lesions (C-PNETs, 11%). To ensure consistent comparisons of overall (OS) and disease-free (DFS) survival outcomes between the 3 groups, the patients were matched according to the World Health Organization (WHO) grade and tumor height.
RESULTS
Overall, the rate of correlation between the preoperative and pathological diagnoses was low in the C-PNET group (33%, P = 0.03). None of the 24 patients (23%) with metastatic disease at the time of surgery were in the C-PNET group. Furthermore, significantly more parenchyma-sparing resections (P = 0.039) and fewer enlarged resections (P = 0.019) were achieved in the C-PNET group. C-PNET group had a significantly lower node invasion rate than the S-PNET and M-PNET groups (8% vs. 41% and 24%, P = 0.004). Although median OS was comparable in all 3 groups before (P = 0.3) and after (P = 0.18) matching, higher median DFS was observed in the C-PNET group than in the other groups after matching (P = 0.038).
CONCLUSION
C-PNET was associated with a better prognosis than PNET with a solid component. The results support a wait-and-see policy in cases wherein a reliable preoperative diagnosis remains challenging.
Topics: Humans; Neuroectodermal Tumors, Primitive; Neuroendocrine Tumors; Pancreatic Neoplasms; Prognosis; Retrospective Studies
PubMed: 32799893
DOI: 10.1186/s12957-020-01994-6 -
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 -
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 -
World Journal of Clinical Cases Sep 2022Rhabdomyosarcoma is a soft tissue tumor of primitive mesenchymal cells origin, occurring predominantly in children and adolescents, but extremely rare in adults and the...
BACKGROUND
Rhabdomyosarcoma is a soft tissue tumor of primitive mesenchymal cells origin, occurring predominantly in children and adolescents, but extremely rare in adults and the data regarding its treatment are sparse. Here, we would like to share our experience in the treatment of a locally advanced primary embryonal rhabdomyosarcoma of cervix in a 39-year-old female.
CASE SUMMARY
The patient was admitted with symptoms of intermenstrual bleeding and postcoital bleeding for six months. Physical examination revealed a friable, polyp-like mass (5 cm × 5 cm) in her cervix protruding into the vagina, while the uterus was mobile and normal-sized. Colposcopy-directed biopsy was performed, and a pathological diagnosis of embryonal rhabdomyosarcoma was made. Magnetic resonance imaging of the pelvis showed that the cervical volume was significantly increased, with a hypointense and hyperintense soft tissue mass on the right side, invading the cervical stroma; the mass was 5 cm × 5 cm with a clear boundary and confined to the cervix; there were no obvious findings indicating tumor invasion in the vaginal wall, parametrium, or pelvic wall; no enlarged lymph nodes were observed in the pelvic cavity. Based on our findings, the tumor was classified as stage IA according to the intergroup rhabdomyosarcoma studies criteria and IB3 stage according to The International Federation of Gynecology and Obstetrics 2018. The patient underwent two courses of neoadjuvant chemotherapy and a partial remission was achieved. Subsequently, she underwent laparoscopic radical hysterectomy, bilateral salpingo-oophrectomy and pelvic lymph node dissection and there were no risk factors revealed by postoperative pathological examination. Adjuvant chemotherapy was performed after surgery. The patient was disease-free until the last follow-up, 49 mo after completing the entire treatment.
CONCLUSION
Our experience suggests that neoadjuvant vincristine, dactinomycin, and cyclophosphamide chemotherapy followed by radical surgery and adjuvant chemotherapy might be reasonable therapeutic option for bulky cervical rhabdomyosarcoma in adults without fertility desire. Since large-scale studies on such rare conditions are rather impossible, further case reports and systematic reviews could help optimize the treatment of primary, bulky cervical rhabdomyosarcoma in adults.
PubMed: 36159439
DOI: 10.12998/wjcc.v10.i26.9454 -
Medicine Nov 2020Primitive neuroectodermal tumor (PNET) of the urinary bladder is a highly aggressive tumor with high local recurrence and distant metastasis rates in cases of incomplete... (Review)
Review
RATIONALE
Primitive neuroectodermal tumor (PNET) of the urinary bladder is a highly aggressive tumor with high local recurrence and distant metastasis rates in cases of incomplete excision. We report a case of a young female patient, in whom early laparoscopic radical cystectomy combined with standard lymph node dissection and a modified vincristine, doxorubicin hydrochloride, and cyclophosphamide (VAC) chemotherapy regimen was controversial. Because PNET of the urinary bladder is a rare malignancy, the standard treatment regimen has not yet been established. It is not clear whether surgery combined with postoperative chemotherapy for PNET patients may be superior to surgery alone on long term survival.
PATIENT CONCERNS
The patient was a 45-year-old Chinese woman who complained of lower urinary tract symptoms, including urgency, frequency, and difficulty in urination, for 2 months.
DIAGNOSES
PNET.
INTERVENTIONS
The patient underwent laparoscopic radical cystectomy and standard lymph node dissection, combined with modified VAC chemotherapy regimens.
OUTCOMES
After undergoing radical surgery in 2018, the patient completed 6 courses of adjuvant chemotherapy. Abdominal and thorax computed tomography scanning was performed 3, 6, 9, and 12 months after the surgery was completely free of tumor. The patient is still alive with no signs of recurrent disease 2 years after diagnosis.
LESSONS
Radical surgery and standard lymphadenectomy combined with adjuvant chemotherapy may be essential to improve the prognosis of PNET of the urinary bladder.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Child; Combined Modality Therapy; Cyclophosphamide; Cystectomy; Dactinomycin; Female; Humans; Laparoscopy; Lymph Node Excision; Male; Middle Aged; Neuroectodermal Tumors, Primitive; Treatment Outcome; Urinary Bladder Neoplasms; Vincristine
PubMed: 33157954
DOI: 10.1097/MD.0000000000023032