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1.
Cancer Res Commun ; 3(8): 1514-1523, 2023 08.
Article in English | MEDLINE | ID: mdl-37575280

ABSTRACT

Purpose: We conducted a phase II randomized noncomparative window of opportunity (WOO) trial to evaluate the inhibition of cellular proliferation and the modulation of immune microenvironment after treatment with olaparib alone or in combination with cisplatin or durvalumab in patients with operable head and neck squamous cell carcinoma (HNSCC). Experimental Design: Forty-one patients with HNSCC were randomized to cisplatin plus olaparib (arm A), olaparib alone (arm B), no treatment (arm C) or durvalumab plus olaparib (arm D). The primary endpoint was to evaluate the percentage of patients in each arm that achieved a reduction of at least 25% in Ki67. Secondary endpoints included objective response rate (ORR), safety, and pathologic complete response (pCR) rate. Paired baseline and resection tumor biopsies and blood samples were evaluated for prespecified biomarkers. Results: A decrease in Ki67 of at least 25% was observed in 44.8% of treated patients, as measured by quantitative immunofluorescence. The ORR among treated patients was 12.1%. pCR was observed in 2 patients. Two serious adverse events occurred in 2 patients.Programmed death ligand 1 (PD-L1) levels [combined positive score (CPS)] were significantly higher after treatment in arms A and D. Expression of CD163 and colony-stimulating factor 1 receptor (CSF1R) genes, markers of M2 macrophages, increased significantly posttreatment whereas the expression of CD80, a marker of M1 macrophages, decreased. Conclusion: Preoperative olaparib with cisplatin or alone or with durvalumab was safe in the preoperative setting and led to decrease in Ki67 of at least 25% in 44.8% of treated patients. Olaparib-based treatment modulates the tumor microenvironment leading to upregulation of PD-L1 and induction of protumor features of macrophages. Significance: HNSCC is characterized by defective DNA repair pathways and immunosuppressive tumor microenvironment. PARP inhibitors, which promote DNA damage and "reset" the inflammatory tumor microenvironment, can establish an effective antitumor response. This phase II WOO trial in HNSCC demonstrated the immunomodulatory effects of PARP inhibitor-induced DNA damage. In this chemo-naïve population, PARP inhibitor-based treatment, reduced tumor cell proliferation and modulated tumor microenvironment. After olaparib upregulation of PD-L1 and macrophages, suggests that combinatorial treatment might be beneficial. Synopsis: Our WOO study demonstrates that preoperative olaparib results in a reduction in Ki67, upregulation of PD-L1 CPS, and induction of protumor features of macrophages in HNSCC.


Subject(s)
Antineoplastic Agents , Head and Neck Neoplasms , Humans , Squamous Cell Carcinoma of Head and Neck/drug therapy , Cisplatin/adverse effects , B7-H1 Antigen , Poly(ADP-ribose) Polymerase Inhibitors , Ki-67 Antigen , Head and Neck Neoplasms/drug therapy , Tumor Microenvironment
2.
Psychiatr Genet ; 32(6): 246-248, 2022 12 01.
Article in English | MEDLINE | ID: mdl-36354139

ABSTRACT

A considerable group of patients suffering from mental health disorders do not respond adequately to pharmacological treatment. For the purposes of precision and personalized medicine, pharmacogenomics has been developed as a valuable and promising tool. The technology of identifying single nucleotide polymorphisms and genotyping supplies clinicians, and therefore their patients, with the opportunity of avoiding long-lasting 'trial and error' periods, reducing the risk of manifesting disturbing adverse effects during treatment. Consequently, better adherence to treatment and clinical response can be achieved, contributing to personalized treatment planning, according to a person's genetic profile and needs. In the present report, we present a case of an individual diagnosed with bipolar affective disorder type I, who showed resistance to pharmacological treatment and underwent through pharmacogenomic investigations, in order to identify the appropriate medication for the best possible clinical response.


Subject(s)
Bipolar Disorder , Humans , Bipolar Disorder/diagnosis , Bipolar Disorder/drug therapy , Bipolar Disorder/genetics , Mania , Pharmacogenetics , Mood Disorders
3.
Article in English | MEDLINE | ID: mdl-35190089

ABSTRACT

The aim of this study is to analyze patterns and volumes of patients visiting ENT emergency departments during periods of community lockdowns given the newness of this situation and to assess the variation in numbers of visits and examine whether their reduction equally affects all categories of visit causation or whether it is limited to diseases not considered as emergencies. A retrospective descriptive study was conducted on prospectively collected registry data on patients of all age groups visited the emergency ENT department during the period of nationwide lockdown. Patients were grouped in 9 categories, according to the cause of visit the ENT emergency department. A total of 201 patients visited the ENT emergency department. The retrospective analysis of the data during the same period in the years 2013-2019 showed a reduction of 73% in total visits (mean total visits number between 2013 and 2019 was 745.29±20.0143). A statistically significant reduction in visitation was found in all categories studied with the exception of foreign body ingestion - aspiration. Patients with General ENT symptoms, mild epistaxis cases, otology cases, vertigo cases, uncomplicated infectious cases showed a statistically significant reduction in numbers and were treated empirically. Swallowing foreign body cases did not show statistically significant reduction. Limitation of movement and the lockdown itself, led to reduction of trauma cases. Surprisingly, there was also a reduction in oncology cases and an increase in numbers of these cases can be expected in the near future.


Subject(s)
COVID-19 , Communicable Disease Control , Emergency Service, Hospital , Humans , Pandemics , Retrospective Studies , SARS-CoV-2
4.
Acta otorrinolaringol. esp ; 73(1): 56-60, feb 2022.
Article in English | IBECS | ID: ibc-203222

ABSTRACT

The aim of this study is to analyze patterns and volumes of patients visiting ENT emergency departments during periods of community lockdowns given the newness of this situation and to assess the variation in numbers of visits and examine whether their reduction equally affects all categories of visit causation or whether it is limited to diseases not considered as emergencies. A retrospective descriptive study was conducted on prospectively collected registry data on patients of all age groups visited the emergency ENT department during the period of nationwide lockdown. Patients were grouped in 9 categories, according to the cause of visit the ENT emergency department. A total of 201 patients visited the ENT emergency department. The retrospective analysis of the data during the same period in the years 2013–2019 showed a reduction of 73% in total visits (mean total visits number between 2013 and 2019 was 745.29±20.0143). A statistically significant reduction in visitation was found in all categories studied with the exception of foreign body ingestion – aspiration. Patients with General ENT symptoms, mild epistaxis cases, otology cases, vertigo cases, uncomplicated infectious cases showed a statistically significant reduction in numbers and were treated empirically. Swallowing foreign body cases did not show statistically significant reduction. Limitation of movement and the lockdown itself, led to reduction of trauma cases. Surprisingly, there was also a reduction in oncology cases and an increase in numbers of these cases can be expected in the near future. (AU)


El objetivo de este estudio es analizar los patrones y los volúmenes de pacientes que visitan los servicios de urgencias de ORL durante los periodos de cierre de la comunidad, dada la novedad de esta situación, así como evaluar la variación en el número de visitas y examinar si su reducción afecta por igual a todas las categorías de visitas o si se limita a las enfermedades no consideradas como urgentes. Se realizó un estudio descriptivo retrospectivo a partir de los datos de registro recogidos prospectivamente sobre los pacientes de todos los grupos de edad que visitaron el servicio de urgencias de ORL durante el periodo de bloqueo nacional. Los pacientes se agruparon en 9 categorías, según la causa de visita al servicio de urgencias de ORL. Un total de 201 pacientes visitaron el servicio de urgencias de ORL. El análisis retrospectivo de los datos durante el mismo periodo en los años 2013 a 2019 mostró una reducción del 73% en el total de visitas (la media del número de visitas totales entre 2013 a 2019 fue de 745,29±20,0143). Se encontró una reducción estadísticamente significativa de las visitas en todas las categorías estudiadas con la excepción de la ingestión de cuerpos extraños/aspiración. Los pacientes con síntomas de ORL general, los casos de epistaxis leve, los casos de otología, los casos de vértigo, los casos infecciosos no complicados mostraron una reducción estadísticamente significativa en el número y fueron tratados empíricamente. Los casos de cuerpos extraños por ingestión no mostraron una reducción estadísticamente significativa. La limitación de los movimientos y el propio encierro permitieron reducir los casos de traumatismos. Sorprendentemente, también se redujeron los casos de oncología y cabe esperar un aumento del número de estos casos en un futuro próximo.


Subject(s)
Humans , Health Sciences , Severe acute respiratory syndrome-related coronavirus , Otolaryngology , Emergency Medicine , Epidemiology, Descriptive
5.
Ann Otol Rhinol Laryngol ; 131(11): 1194-1201, 2022 Nov.
Article in English | MEDLINE | ID: mdl-34841913

ABSTRACT

OBJECTIVES: To evaluate clinical and microbiological findings that are correlated with abscess formation in adult acute epiglottitis (AE). METHODS: We reviewed 140 cases of adult AE. Demographic, clinical, imaging, and microbiological findings are analyzed for all patients with AE in comparison to those with epiglottic abscess (EA). RESULTS: A total of 113 patients presented with AE and 27 presented or progressed to EA (19.3%). Age, sex, seasonality, smoking, body mass index (BMI), and comorbidities were statistically insignificant between the 2 groups. Muffled voice (P < .013), respiratory distress (P < .001), and pre-existence of epiglottic cyst (P < .001) are symptoms and signs connected with abscess formation. A total of 120 patients were treated conservatively. Surgical treatment was performed on 20 patients with EA. About 72 out of 80 cultures revealed monomicrobial infection. Mixed flora was isolated in 8 patients with EA. Streptococcus was isolated in 51 out of 80 positive cultures (64%). Haemophilus Influenza (Hib) was not isolated in any sample. EA and mixed flora relates to a higher rate of airway intervention (P < .001). CONCLUSION: A high level of suspicion for abscess formation is required if clinical examination reveals dyspnea, muffled voice, or an epiglottic cyst in adult with AE. The existence of EA doubles the duration of hospitalization. EA is typically found on the lingual surface of the epiglottis. Supraglottic or deep neck space expansion should be treated surgically. EA is associated with a mixed flora and a higher rate of airway obstruction. Streptococcus is discovered to be the most common pathogen.


Subject(s)
Airway Obstruction , Cysts , Epiglottitis , Laryngeal Diseases , Abscess/diagnosis , Acute Disease , Adult , Airway Obstruction/diagnosis , Dyspnea , Epiglottis , Epiglottitis/therapy , Female , Humans , Laryngeal Diseases/complications , Male
6.
Cureus ; 13(6): e15425, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34262800

ABSTRACT

Metastatic involvement of the thyroid occurs rarely, by either hematogenous spread or direct extension from adjacent organs. The most frequent metastatic tumors are clear cell, renal cell, lung, breast, and squamous cell carcinoma. The occurrence of osteosarcoma and papillary thyroid carcinoma in the same patient is rare, with only a few reported cases in the literature. On the other hand, only one case of osteosarcoma thyroid metastasis has so far been reported. We herewith present another case with metastatic osteosarcoma and multifocal papillary thyroid carcinoma presenting as a collision tumor and review the relevant literature.

7.
Article in English, Spanish | MEDLINE | ID: mdl-33712296

ABSTRACT

The aim of this study is to analyze patterns and volumes of patients visiting ENT emergency departments during periods of community lockdowns given the newness of this situation and to assess the variation in numbers of visits and examine whether their reduction equally affects all categories of visit causation or whether it is limited to diseases not considered as emergencies. A retrospective descriptive study was conducted on prospectively collected registry data on patients of all age groups visited the emergency ENT department during the period of nationwide lockdown. Patients were grouped in 9 categories, according to the cause of visit the ENT emergency department. A total of 201 patients visited the ENT emergency department. The retrospective analysis of the data during the same period in the years 2013-2019 showed a reduction of 73% in total visits (mean total visits number between 2013 and 2019 was 745.29±20.0143). A statistically significant reduction in visitation was found in all categories studied with the exception of foreign body ingestion - aspiration. Patients with General ENT symptoms, mild epistaxis cases, otology cases, vertigo cases, uncomplicated infectious cases showed a statistically significant reduction in numbers and were treated empirically. Swallowing foreign body cases did not show statistically significant reduction. Limitation of movement and the lockdown itself, led to reduction of trauma cases. Surprisingly, there was also a reduction in oncology cases and an increase in numbers of these cases can be expected in the near future.

8.
Eur Arch Otorhinolaryngol ; 278(11): 4587-4592, 2021 Nov.
Article in English | MEDLINE | ID: mdl-33559743

ABSTRACT

PURPOSE: The aim of this retrospective review study is to evaluate Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score as an indicative parameter in early detecting cervical necrotizing fasciitis (CNF) from deep neck infections (DNI). METHODS: We reviewed 12 cases of CNF and 538 cases of non-necrotizing deep neck infection hospitalized in our hospital over the last decade. Cervical necrotizing fasciitis was histologically confirmed. RESULTS: Using an LRINEC score of 6 as a cutoff sensitivity was calculated at 100% (95% CI 99.9-100) and specificity 72.5% (95% CI 72.4-72.6). Negative predicted value (NPV) was 100% and positive predicted value (PPV) was 7.5%. C-reactive protein (CRP), white blood count (WBC), and glucose (Glu) levels have a higher correlation. Haemoglobin (Hb), sodium (Na), and creatinine (Cr) do not seem to have a big impact in our study. CONCLUSION: LRINEC score proves to be a useful "rule-out" tool that works on the safe side with high sensitivity and poor specificity. WBC, CRP, and Glu seem to be the most significant variables of the LRINEC score. Hb, Na, and Cr make the score safer. Decision for surgery must be based on medical history, clinical symptoms and signs, imaging findings, and laboratory tests and not according to the LRINEC score itself.


Subject(s)
Fasciitis, Necrotizing , C-Reactive Protein , Creatinine , Fasciitis, Necrotizing/diagnosis , Fasciitis, Necrotizing/etiology , Humans , Neck , Retrospective Studies
9.
Int J Spine Surg ; 15(6): 1201-1209, 2021 Dec.
Article in English | MEDLINE | ID: mdl-35086878

ABSTRACT

PURPOSE: Degeneration of the intervertebral disc is considered to be central in pain pathogenesis in patients suffering from chronic low back pain (LBP). In recent years, the injection of mesenchymal stromal cells (MSCs) into the disc to arrest or reverse the degenerative process has been proposed as an alternative therapy. The aim of the present study was to investigate the feasibility of using iron-labeled MSCs for intradiscal injection in patients with long-standing LBP. METHODS: Ten patients (7 men, 3 women, mean age 40 years, range 26-53) with chronic LBP and confirmed disc degeneration on magnetic resonance imaging (MRI) were recruited from the waiting list for planned surgery. Injection of autologous, expanded, and iron-labeled bone marrow-derived MSCs (BM-MSCs) into 1 or 2 disc levels was undertaken. Follow-up consisted of monitoring of adverse events, regular MRI examinations, and collection of patient-reported outcome measures (PROMs) for a minimum of 2 years. RESULTS: No complications could be detected, neither clinically nor on MRI. No statistically significant improvement was seen for PROMs on a group level up to 2 years postinjection. Three of 10 patients opted to proceed with the initially planned surgery within the first year and 2 more within 3 years postinjection. CONCLUSION: Results from this pilot cohort study show that injection of autologous expanded iron-labeled BM-MSCs is a safe procedure, in accordance with the existing body of evidence. The clinical result warrants further larger studies. LEVEL OF EVIDENCE: 4 for therapeutic studies.

10.
Water Sci Technol ; 82(12): 2691-2710, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33341763

ABSTRACT

The rise of Internet of Things (IoT), coupled with the advances in Artificial Intelligence technologies and cloud-based applications, have caused fundamental changes in the way societies behave. Enhanced connectivity and interactions between physical and cyber worlds create 'smart' solutions and applications to serve society's needs. Water is a vital resource and its management is a critical issue. ICT achievements gradually deployed within the water industry provide an alternative, smart and novel way to improve water management efficiently. Contributing to this direction, we propose a unified framework for urban water management, exploiting state-of-the-art IoT solutions for remote telemetry and control of water consumption in combination with machine learning-based processes. The SMART-WATER platform aims to foster water utility companies by enhancing water management and decision-making processes, providing innovative solutions to consumers for smart water utilisation.


Subject(s)
Artificial Intelligence , Water , Industry , Technology
11.
Cureus ; 12(7): e9028, 2020 Jul 06.
Article in English | MEDLINE | ID: mdl-32775107

ABSTRACT

Retropharyngeal abscess (RPA) in adults is a potentially life-threatening condition that relates in most of the cases with local trauma. Non-traumatic RPA complicated by spinal osteomyelitis and epidural abscess is a rare entity in immunocompetent adults and represents an emergency medical condition when the patient develops neurologic symptoms. This article presents a case of non-traumatic RPA complicated by spinal osteomyelitis and epidural abscess in a 77-year-old male with the free past medical history. We highlight the importance of early and meticulous daily drainage as well as sequential MRI scanning for early diagnosis, treatment and follow-up for signs of vertebral involvement. The patient had a full recovery and was subsequently discharged with per os four-month antibiotic treatment. The definitive mechanism is unclear for non-traumatic cases with "hematogenous path" being the closest description. Spontaneous RPA can develop from bacteria infection spread of adjacent structures, local inflammatory process and microthrombosis formation can impair the blood supply of vertebral and intervertebral disks.

12.
Cureus ; 12(11): e11781, 2020 Nov 30.
Article in English | MEDLINE | ID: mdl-33409028

ABSTRACT

Pott's puffy tumor (PPT) represents a rare complication of frontal sinusitis, and it is considered as a subperiosteal abscess of the frontal bone based on osteomyelitis. We report two adult PPT patients and discuss the treatment plan as well as the correct timing of surgical intervention. Clinical examination revealed sinusitis with puss, and imaging findings showed bony erosion of the dorsal wall of the frontal sinus in both patients. In case 1, a "wait and see" approach was followed with remission of the patient's symptoms, and a Draf IIb type was performed 21 days after discharge. In case 2, worsening of symptoms led to surgical drainage through a Lynch incision followed by 20 days of intravenous antibiotic treatment. Then a Draf type IIa was performed. Both patients received antibiotic therapy over the course of six weeks and had full recovery. We highlight the importance of the correct timing of surgical intervention as it is depended on the clinical and radiological findings. The timing to performing radical drainage surgery including external or endoscopic frontal sinus surgery is not determined in the literature. Worsening of common symptoms and neurological signs in adult PPT patients means by default an immediate surgical intervention. Reduction of symptoms and antibiotic treatment response means that surgery should be delayed and performed in a surgical field free of inflammation.

13.
Oral Oncol ; 94: 93-100, 2019 07.
Article in English | MEDLINE | ID: mdl-31178219

ABSTRACT

OBJECTIVES: Chemoradiation can induce immunogenic (ICD) or tolerogenic cell death. ICD relies on the generation of damage-associated molecular patterns which can stimulate toll-like receptors (TLRs). We sought to determine whether we can predict responses to chemoradiation by measuring surrogate biomarkers of ICD in a cohort of patients with locally advanced (LA) head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: In a cohort of 113 LA HNSCC pts we evaluated expression of TLR4, TLR7 and TLR9 in the EpCAM + circulating tumor cell (CTC) fraction at baseline and after cisplatin chemoradiation. We also quantified changes in chemokines CXCL10, CXCL16 and IL-2R in the serum. RESULTS: Seventy three patients had evaluable specimens. Among cases with biomarker assessment at baseline and post treatment, 36.8% had an increase in CXCL10 levels (p = 0.022), 73.7% had an increase in CXCL16 levels (p = 0.002) and 63.8% had an increase in IL2Ra levels (p = 0.032) with treatment. 52.0% of evaluable cases at baseline and post-treatment had an increase in TLR4 levels (p = 0.996), 42.9% had an increase in TLR7 levels (p = 0.042) and 27.7% had increase in TLR9 levels (p = 0.011) with treatment. CXCL10 levels at baseline were significantly associated with PFS and OS (p = 0.010 and p = 0.032, respectively). CONCLUSIONS: Our results suggest that chemoradiation leads to quantifiable effects in surrogate markers of ICD. These effects may inform trials combining chemoradiation with immune checkpoint inhibitors. In addition, CXCL10 has prognostic effect in pts treated with chemoradiation.


Subject(s)
Cell Death/genetics , Neoplastic Cells, Circulating/metabolism , Squamous Cell Carcinoma of Head and Neck/radiotherapy , Adolescent , Adult , Aged , Aged, 80 and over , Chemoradiotherapy/methods , Female , Humans , Male , Middle Aged , Prognosis , Squamous Cell Carcinoma of Head and Neck/pathology , Treatment Outcome , Young Adult
14.
Stem Cells Dev ; 28(17): 1203-1211, 2019 09 01.
Article in English | MEDLINE | ID: mdl-31237488

ABSTRACT

Low back pain is a major health issue and one main cause to this condition is believed to be intervertebral disc (IVD) degeneration. Stem cell therapy for degenerated discs using mesenchymal stromal cells (MSCs) has been suggested. The aim of the study was to investigate the presence and distribution pattern of autologous MSCs transplanted into degenerated IVDs in patients and explanted posttransplantation. IVD tissues from four patients (41, 45, 47, and 47 years of age) participating in a clinical feasibility study on MSC transplantation to degenerative discs were investigated. Three patients decided to undergo fusion surgery at time points 8 months and one patient at 28 months posttransplantation. Pretransplantation, MSCs from bone marrow aspirate were isolated by centrifugation in FICOLL® test tubes and cultured (passage 1). Before transplantation, MSCs were labeled with 1 mg/mL iron sucrose (Venofer®) and 1 × 106 MSCs were transplanted into degenerated IVDs. At the time point of surgery, IVD tissues were collected. IVD tissue samples were fixated, embedded in paraffin, and sections prepared. IVD samples were stained with Prussian Blue, by which iron deposits are visualized and examined (light microscopy). Immunohistochemistry (IHC), including SOX9 (sex determining region Y box 9), Coll2A1 (collagen 2A1), and cell viability (TUNEL) were performed. Cells positive for iron deposits were observed in IVD tissues (3/4 patients). The cells/iron deposits were observed in clusters and/or as solitary cells in regions in IVD tissue samples [regions of interest (ROIs)]. By IHC, SOX9- and Coll2A1-positive cells were detected in the same regions as the detected cells/iron deposits. A few nonviable cells were detected by TUNEL assay in ROIs. Results demonstrated that MSCs, labeled with iron sucrose, transplanted into degenerated IVDs were detectable 8 months posttransplantation. The detected cellular activity indicates that MSCs have differentiated into chondrocyte-like cells and that the injected MSCs and/or their progeny have survived since the cells were found in large cluster and as solitary cells which were distributed at different parts of the IVD.


Subject(s)
Intervertebral Disc Degeneration/therapy , Low Back Pain/therapy , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/metabolism , Adult , Cell Movement , Cells, Cultured , Chondrogenesis , Collagen Type II/genetics , Collagen Type II/metabolism , Female , Humans , Injections, Spinal , Intervertebral Disc Degeneration/pathology , Iron/metabolism , Low Back Pain/pathology , Male , Mesenchymal Stem Cell Transplantation/adverse effects , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/physiology , Middle Aged , SOX9 Transcription Factor/genetics , SOX9 Transcription Factor/metabolism
15.
Phys Chem Chem Phys ; 20(44): 28026-28038, 2018 Nov 14.
Article in English | MEDLINE | ID: mdl-30383048

ABSTRACT

The current study employs Grand Canonical Monte Carlo simulations in order to calculate the process efficiency of separating CH4 + CO2 gas mixtures by utilizing structure sI clathrate hydrates. The temperature and pressure conditions examined in the current study resemble those used in industry. The simulation results are compared with experimental measurements and very good agreement is found. In addition, hydrate cage occupancies are compared with experimental measurements and calculations using a commercial simulator. Excellent agreement is found only for the case of large cages, while for the case of small cages significant disagreement is observed.

16.
Stem Cells Dev ; 24(20): 2403-12, 2015 Oct 15.
Article in English | MEDLINE | ID: mdl-26076769

ABSTRACT

For evaluation of cell therapy applications, it is of interest to be able to trace and observe cellular distribution of the transplanted cells. The aim with the study was to examine viability, traceability, and multilineage capability of iron sucrose-labeled mesenchymal stem cells (MSCs) after transplantation into lapine intervertebral discs (IVDs). MSCs were collected from three human donors, age 31-50 years, and IVDs from 12 rabbits, age 3 months. MSCs were isolated from the bone marrow and cultured using standard protocols. Iron sucrose labeling of MSCs was performed in Dulbecco's Modified Eagle's Medium-low glucose with Venofer(®). The iron sucrose-labeled MSCs were differentiated into the adipogenic, osteogenic, and chondrogenic lineages. Results were evaluated using Oil red, von Kossa, Alcian blue, and collagen II (immunohistochemistry). For the animal experiments, iron sucrose-labeled MSCs and nonlabeled MSCs were injected into lapine IVDs (LI-LIV level). After transplantation, at the time points of 1 and 3 months, IVDs were collected and cells were analyzed for cell viability (fluorescence-activated cell sorting). The lapine IVDs were collected and examined for presence of cells positive for iron deposits using Berliner blue staining. Differentiation of the iron sucrose-labeled MSCs into adipogenic (lipid droplets), osteogenic (calcium deposits), and chondrogenic lineage (proteoglycan/collagen II accumulation) (3/3 donors) was observed in vitro. After transplantation, the mean cell viability for iron-labeled MSCs/IVD cells was 99%, for nonlabeled MSCs/IVD cells was 95%, and for control IVD cells was 99% at a time point of 1 month. At a time point of 3 months, mean cell viability was 73% for iron sucrose-labeled MSCs/IVD cells, for nonlabeled MSCs/IVD cells was 77%, and for control IVD cells was 98%. At the time point of 1 month, cells positive for iron deposits were detected sparsely distributed in IVDs (tissue sections) in 4/4 animals and at the time point of 3 months in 4/4 animals. The results indicate that iron sucrose can be used as a cell tracer with a stable detection potential in tissues (histologies). This may be an important evaluation tool for understanding stem cell distribution/function after transplantation into degenerated cartilaginous tissues.


Subject(s)
Cell Differentiation/physiology , Cell Lineage , Intervertebral Disc/cytology , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , Adult , Animals , Cell- and Tissue-Based Therapy/methods , Cells, Cultured , Disease Models, Animal , Female , Humans , Immunohistochemistry/methods , Male , Mesenchymal Stem Cell Transplantation/methods , Rabbits , Transplantation, Heterologous/methods
17.
18.
Stem Cells Dev ; 23(21): 2568-80, 2014 Nov 01.
Article in English | MEDLINE | ID: mdl-25036548

ABSTRACT

For evaluation of cell therapy strategies using human mesenchymal stem cells (hMSCs), it is important to be able to trace transplanted cells and their distribution in tissues, for example, cartilage, over time. The aim of the study was to determine effects on cell viability, traceability, and chondrogenic differentiation of hMSCs after iron labeling with iron sucrose. hMSCs were collected (seven donors, 13-57 years) from patients undergoing spinal surgery. Two subsets of experiments were performed. (1) Iron labeling of hMSCs: 1 mg/mL of Venofer(®) (iron sucrose) was added (16 h) to cultures. hMSCs were examined for uptake of iron sucrose (Prussian blue staining) and cell viability (flow cytometry). (2) Iron-labeled hMSCs (passage 4) (n=4, pellet mass), 200,000 cells/tube, were cultured (DMEM-HG) with 10 ng/mL TGFß and compared with controls (from each donor). The pellets were harvested at days 7, 14, and 28. Real-time PCR, IHC, and histology were used to evaluate SOX9, ACAN, C6S, and COL2A1 expression. Mean number of cells containing iron deposits was 98.1% and mean cell viability was 92.7% (no significant difference compared with unlabeled control cells). Pellets containing iron-labeled cells expressed COL2A1 on protein level (all time points), in similar levels as controls, and glycosaminoglycan accumulation was observed in iron-labeled pellets (day 14 or day 28). Results were supported by the expression of chondrogenic genes SOX9, ACAN, and COL2A1. The results in vitro indicate that iron sucrose can be used as a cell tracer for evaluation of cellular distribution in vivo after transplantation of MSCs and thus contribute with important knowledge when exploring new treatment strategies for degenerated cartilaginous tissues.


Subject(s)
Cell Differentiation/physiology , Chondrocytes/physiology , Ferric Compounds/metabolism , Mesenchymal Stem Cells/metabolism , Sucrose/metabolism , Adolescent , Adult , Aggrecans/genetics , Biomarkers/metabolism , Cell Differentiation/genetics , Cell Survival/genetics , Cell Survival/physiology , Cells, Cultured , Chondrocytes/cytology , Chondrocytes/metabolism , Chondrogenesis/genetics , Collagen Type II/genetics , Ferric Compounds/chemistry , Ferric Oxide, Saccharated , Flow Cytometry , Gene Expression/drug effects , Glucaric Acid , Humans , Immunohistochemistry , Immunophenotyping , Iron/chemistry , Iron/metabolism , Mesenchymal Stem Cells/chemistry , Mesenchymal Stem Cells/cytology , Middle Aged , Reverse Transcriptase Polymerase Chain Reaction , SOX9 Transcription Factor/genetics , Staining and Labeling/methods , Sucrose/chemistry , Time Factors , Transforming Growth Factor beta/pharmacology , Young Adult
19.
J Pediatr Hematol Oncol ; 36(5): 407-9, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24577542

ABSTRACT

Occurrence of malignancy in a thyroglossal duct cyst (TDC) in children and adolescents is very rare, preoperative diagnosis is a challenge, and appropriate management is still debated. We report a 19-year-old male patient referred for a midline neck mass diagnosed as an atypical TDC after initial and subsequent investigations. Ultrasound-guided fine-needle aspiration (FNA) of the mass was diagnostic for papillary thyroid carcinoma. Sistrunk procedure and total thyroidectomy were performed. Histologic analysis confirmed the presence of papillary thyroid carcinoma within TDC, infiltrating surrounding soft tissues. Postoperatively, radioiodine ablation treatment was administered, followed by TSH suppression therapy.


Subject(s)
Carcinoma, Papillary/diagnosis , Thyroglossal Cyst/pathology , Thyroid Neoplasms/diagnosis , Adolescent , Biopsy, Fine-Needle , Carcinoma, Papillary/therapy , Combined Modality Therapy , Humans , Male , Prognosis , Thyroid Neoplasms/therapy , Ultrasonography , Young Adult
20.
Arab J Gastroenterol ; 14(1): 20-3, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23622805

ABSTRACT

Adenocarcinoma and lymphoma represent the two most common malignant tumours of the stomach, with both neoplasms being associated with infection by Helicobacter pylori. However, the presence of lymphoma and adenocarcinoma in the same patient is a rare entity with synchronous neoplasms being more common than metachronous types. We report a case of stage IV gastric MALT lymphoma of the gastric angle with infiltration of the bone marrow successfully treated with chemotherapy and the occurrence of metachronous early gastric adenocarcinoma of the fundus presenting 1 year after the diagnosis of the lymphoma.


Subject(s)
Adenocarcinoma/diagnosis , Lymphoma, B-Cell, Marginal Zone/pathology , Neoplasms, Second Primary/diagnosis , Stomach Neoplasms/diagnosis , Stomach Neoplasms/therapy , Adenocarcinoma/surgery , Aged , Gastroscopy , Humans , Lymphoma, B-Cell, Marginal Zone/diagnosis , Lymphoma, B-Cell, Marginal Zone/drug therapy , Male , Neoplasms, Second Primary/surgery , Remission Induction
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