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1.
PLoS Biol ; 22(5): e3002640, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38814900

RESUMEN

Glioblastoma, the most aggressive and prevalent form of primary brain tumor, is characterized by rapid growth, diffuse infiltration, and resistance to therapies. Intrinsic heterogeneity and cellular plasticity contribute to its rapid progression under therapy; therefore, there is a need to fully understand these tumors at a single-cell level. Over the past decade, single-cell transcriptomics has enabled the molecular characterization of individual cells within glioblastomas, providing previously unattainable insights into the genetic and molecular features that drive tumorigenesis, disease progression, and therapy resistance. However, despite advances in single-cell technologies, challenges such as high costs, complex data analysis and interpretation, and difficulties in translating findings into clinical practice persist. As single-cell technologies are developed further, more insights into the cellular and molecular heterogeneity of glioblastomas are expected, which will help guide the development of personalized and effective therapies, thereby improving prognosis and quality of life for patients.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Análisis de la Célula Individual , Humanos , Glioblastoma/genética , Glioblastoma/patología , Glioblastoma/terapia , Análisis de la Célula Individual/métodos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/terapia , Transcriptoma , Animales
2.
Genome Med ; 16(1): 51, 2024 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-38566128

RESUMEN

BACKGROUND: A major contributing factor to glioblastoma (GBM) development and progression is its ability to evade the immune system by creating an immune-suppressive environment, where GBM-associated myeloid cells, including resident microglia and peripheral monocyte-derived macrophages, play critical pro-tumoral roles. However, it is unclear whether recruited myeloid cells are phenotypically and functionally identical in GBM patients and whether this heterogeneity is recapitulated in patient-derived orthotopic xenografts (PDOXs). A thorough understanding of the GBM ecosystem and its recapitulation in preclinical models is currently missing, leading to inaccurate results and failures of clinical trials. METHODS: Here, we report systematic characterization of the tumor microenvironment (TME) in GBM PDOXs and patient tumors at the single-cell and spatial levels. We applied single-cell RNA sequencing, spatial transcriptomics, multicolor flow cytometry, immunohistochemistry, and functional studies to examine the heterogeneous TME instructed by GBM cells. GBM PDOXs representing different tumor phenotypes were compared to glioma mouse GL261 syngeneic model and patient tumors. RESULTS: We show that GBM tumor cells reciprocally interact with host cells to create a GBM patient-specific TME in PDOXs. We detected the most prominent transcriptomic adaptations in myeloid cells, with brain-resident microglia representing the main population in the cellular tumor, while peripheral-derived myeloid cells infiltrated the brain at sites of blood-brain barrier disruption. More specifically, we show that GBM-educated microglia undergo transition to diverse phenotypic states across distinct GBM landscapes and tumor niches. GBM-educated microglia subsets display phagocytic and dendritic cell-like gene expression programs. Additionally, we found novel microglial states expressing cell cycle programs, astrocytic or endothelial markers. Lastly, we show that temozolomide treatment leads to transcriptomic plasticity and altered crosstalk between GBM tumor cells and adjacent TME components. CONCLUSIONS: Our data provide novel insights into the phenotypic adaptation of the heterogeneous TME instructed by GBM tumors. We show the key role of microglial phenotypic states in supporting GBM tumor growth and response to treatment. Our data place PDOXs as relevant models to assess the functionality of the TME and changes in the GBM ecosystem upon treatment.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Ratones , Animales , Humanos , Glioblastoma/genética , Glioblastoma/metabolismo , Microglía/metabolismo , Ecosistema , Xenoinjertos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Fenotipo , Modelos Animales de Enfermedad , Células Dendríticas/metabolismo , Microambiente Tumoral/genética
3.
bioRxiv ; 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-36945572

RESUMEN

Background: A major contributing factor to glioblastoma (GBM) development and progression is its ability to evade the immune system by creating an immune-suppressive environment, where GBM-associated myeloid cells, including resident microglia and peripheral monocyte-derived macrophages, play critical pro-tumoral roles. However, it is unclear whether recruited myeloid cells are phenotypically and functionally identical in GBM patients and whether this heterogeneity is recapitulated in patient-derived orthotopic xenografts (PDOXs). A thorough understanding of the GBM ecosystem and its recapitulation in preclinical models is currently missing, leading to inaccurate results and failures of clinical trials. Methods: Here, we report systematic characterization of the tumor microenvironment (TME) in GBM PDOXs and patient tumors at the single-cell and spatial levels. We applied single-cell RNA-sequencing, spatial transcriptomics, multicolor flow cytometry, immunohistochemistry and functional studies to examine the heterogeneous TME instructed by GBM cells. GBM PDOXs representing different tumor phenotypes were compared to glioma mouse GL261 syngeneic model and patient tumors. Results: We show that GBM tumor cells reciprocally interact with host cells to create a GBM patient-specific TME in PDOXs. We detected the most prominent transcriptomic adaptations in myeloid cells, with brain-resident microglia representing the main population in the cellular tumor, while peripheral-derived myeloid cells infiltrated the brain at sites of blood-brain barrier disruption. More specifically, we show that GBM-educated microglia undergo transition to diverse phenotypic states across distinct GBM landscapes and tumor niches. GBM-educated microglia subsets display phagocytic and dendritic cell-like gene expression programs. Additionally, we found novel microglial states expressing cell cycle programs, astrocytic or endothelial markers. Lastly, we show that temozolomide treatment leads to transcriptomic plasticity and altered crosstalk between GBM tumor cells and adjacent TME components. Conclusions: Our data provide novel insights into the phenotypic adaptation of the heterogeneous TME instructed by GBM tumors. We show the key role of microglial phenotypic states in supporting GBM tumor growth and response to treatment. Our data place PDOXs as relevant models to assess the functionality of the TME and changes in the GBM ecosystem upon treatment.

4.
Malar J ; 22(1): 100, 2023 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-36932400

RESUMEN

BACKGROUND: Insecticide resistance is a serious threat to the continued effectiveness of insecticide-based malaria vector control measures, such as long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS). This paper describes trends and dynamics of insecticide resistance and its underlying mechanisms from annual resistance monitoring surveys on Anopheles gambiae sensu lato (s.l.) populations conducted across mainland Tanzania from 2004 to 2020. METHODS: The World Health Organization (WHO) standard protocols were used to assess susceptibility of the wild female An. gambiae s.l. mosquitoes to insecticides, with mosquitoes exposed to diagnostic concentrations of permethrin, deltamethrin, lambdacyhalothrin, bendiocarb, and pirimiphos-methyl. WHO test papers at 5× and 10× the diagnostic concentrations were used to assess the intensity of resistance to pyrethroids; synergist tests using piperonyl butoxide (PBO) were carried out in sites where mosquitoes were found to be resistant to pyrethroids. To estimate insecticide resistance trends from 2004 to 2020, percentage mortalities from each site and time point were aggregated and regression analysis of mortality versus the Julian dates of bioassays was performed. RESULTS: Percentage of sites with pyrethroid resistance increased from 0% in 2004 to more than 80% in the 2020, suggesting resistance has been spreading geographically. Results indicate a strong negative association (p = 0.0001) between pyrethroids susceptibility status and survey year. The regression model shows that by 2020 over 40% of An. gambiae mosquitoes survived exposure to pyrethroids at their respective diagnostic doses. A decreasing trend of An. gambiae susceptibility to bendiocarb was observed over time, but this was not statistically significant (p = 0.8413). Anopheles gambiae exhibited high level of susceptibility to the pirimiphos-methyl in sampled sites. CONCLUSIONS: Anopheles gambiae Tanzania's major malaria vector, is now resistant to pyrethroids across the country with resistance increasing in prevalence and intensity and has been spreading geographically. This calls for urgent action for efficient malaria vector control tools to sustain the gains obtained in malaria control. Strengthening insecticide resistance monitoring is important for its management through evidence generation for effective malaria vector control decision.


Asunto(s)
Anopheles , Insecticidas , Malaria , Piretrinas , Animales , Femenino , Humanos , Resistencia a los Insecticidas , Tanzanía , Mosquitos Vectores , Malaria/epidemiología , Malaria/prevención & control , Piretrinas/farmacología , Insecticidas/farmacología , Control de Mosquitos/métodos
5.
Afr J Lab Med ; 11(1): 1594, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36091353

RESUMEN

Background: Antimicrobial resistance (AMR) is becoming a critical public health issue globally. The World Health Organization launched the Global Antimicrobial Resistance and Use Surveillance System (GLASS) to support the strengthening of the AMR evidence base. Objective: The article describes the evolution of national AMR surveillance systems and AMR data reporting of countries in the African continent between 2017 and 2019, and the constraints, perceived impact and value of the participation in GLASS. Methods: Data on implementation of national surveillance systems and AMR rates were submitted to GLASS between 2017 and 2019 and summarised though descriptive statistics. The information on constraints and perceived impact and value in GLASS participation was collected though a set of questionnaires. Results: Between 2017 and 2019, Egypt, Ethiopia, Madagascar, Malawi, Mali, Mozambique, Nigeria, South Africa, Sudan, Tunisia, Uganda and Zambia submitted data to GLASS. The main constraints listed are linked to scarce laboratory capacity and capability, limited staffing, budget issues, and data management. Moreover, while the data are not yet nationally representative, high resistance rates were reported to commonly-used antibiotics, as the emerging resistance to last treatment options. Conclusion: Despite the limitations, more and more countries in the African continent are working towards reaching a status that will enable them to report AMR data in a complete and systematic manner. Future improvements involve the expansion of routine surveillance capacity for several countries and the implementation of surveys that allow to effectively define the magnitude of AMR in the continent.

6.
Cell ; 185(16): 2899-2917.e31, 2022 08 04.
Artículo en Inglés | MEDLINE | ID: mdl-35914528

RESUMEN

Glioblastomas are incurable tumors infiltrating the brain. A subpopulation of glioblastoma cells forms a functional and therapy-resistant tumor cell network interconnected by tumor microtubes (TMs). Other subpopulations appear unconnected, and their biological role remains unclear. Here, we demonstrate that whole-brain colonization is fueled by glioblastoma cells that lack connections with other tumor cells and astrocytes yet receive synaptic input from neurons. This subpopulation corresponds to neuronal and neural-progenitor-like tumor cell states, as defined by single-cell transcriptomics, both in mouse models and in the human disease. Tumor cell invasion resembled neuronal migration mechanisms and adopted a Lévy-like movement pattern of probing the environment. Neuronal activity induced complex calcium signals in glioblastoma cells followed by the de novo formation of TMs and increased invasion speed. Collectively, superimposing molecular and functional single-cell data revealed that neuronal mechanisms govern glioblastoma cell invasion on multiple levels. This explains how glioblastoma's dissemination and cellular heterogeneity are closely interlinked.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Animales , Astrocitos/patología , Encéfalo/patología , Neoplasias Encefálicas/patología , Glioblastoma/genética , Glioblastoma/patología , Humanos , Ratones , Invasividad Neoplásica , Neuronas/fisiología
7.
Mol Oncol ; 16(17): 3167-3191, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35838338

RESUMEN

In glioblastoma (GBM), tumour-associated microglia/macrophages (TAMs) represent the major cell type of the stromal compartment and contribute to tumour immune escape mechanisms. Thus, targeting TAMs is emerging as a promising strategy for immunotherapy. However, TAM heterogeneity and metabolic adaptation along GBM progression represent critical features for the design of effective TAM-targeted therapies. Here, we comprehensively study the cellular and molecular changes of TAMs in the GL261 GBM mouse model, combining single-cell RNA-sequencing with flow cytometry and immunohistological analyses along GBM progression and in the absence of Acod1 (also known as Irg1), a key gene involved in the metabolic reprogramming of macrophages towards an anti-inflammatory phenotype. Similarly to patients, we identify distinct TAM profiles, mainly based on their ontogeny, that reiterate the idea that microglia- and macrophage-like cells show key transcriptional differences and dynamically adapt along GBM stages. Notably, we uncover decreased antigen-presenting cell features and immune reactivity in TAMs along tumour progression that are instead enhanced in Acod1-deficient mice. Overall, our results provide insight into TAM heterogeneity and highlight a novel role for Acod1 in TAM adaptation during GBM progression.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Animales , Neoplasias Encefálicas/patología , Glioblastoma/metabolismo , Inmunoterapia , Macrófagos/metabolismo , Ratones , Microglía/metabolismo , Microglía/patología , Microambiente Tumoral
8.
Public Health ; 206: 87-93, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35436651

RESUMEN

OBJECTIVES: Elevated waist circumference results from an excessive accumulation of visceral fat, causing an impairment of health. Waist circumference is highly correlated with diabetes, cardiovascular disease, and all-cause mortality. This study aimed to estimate the overall, sex-specific, and region-specific prevalence rates of central obesity in Nigeria. STUDY DESIGN: Systematic review and meta-analysis. METHODS: Online searches of Google Scholar, PubMed, and Scopus were conducted, and studies were selected based on predefined criteria. Random effects model was fitted using inverse variance method with correction using Sidik-Jonkman's estimator. RESULTS: Eighteen studies consisting of 21,859 individuals conducted between 1996 and 2021 were included in the meta-analysis. Thirty-nine percent (95% confidence interval [CI]: 25%-54%, I2 = 99.3%) of adult Nigerians are centrally obese (by International Diabetes Federation criteria). This translates to estimated 46.8 million centrally obese adult Nigerians. More than half (54% [95% CI: 39%-68%]) of adult females are centrally obese. This is four times the prevalence in males (13% [95% CI: 5%-24%]). Southern regions have higher prevalence of central obesity than northern regions (48% vs 18%). The overall mean waist circumference in Nigeria is 83.8 cm (95% CI: 80.8-86.8 cm, I2 = 99.8%, P value is <0.001). CONCLUSIONS: Females, urban residents, and individuals living in the northern part of Nigeria have a high burden of central obesity. Public health measures for halting the epidemic of obesity should be targeted at these high-risk groups.


Asunto(s)
Diabetes Mellitus , Obesidad Abdominal , Adulto , Índice de Masa Corporal , Diabetes Mellitus/epidemiología , Femenino , Humanos , Masculino , Nigeria/epidemiología , Obesidad/epidemiología , Obesidad Abdominal/epidemiología , Prevalencia , Circunferencia de la Cintura
9.
Neuro Oncol ; 24(5): 669-682, 2022 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-34932099

RESUMEN

Phenotypic plasticity has emerged as a major contributor to intra-tumoral heterogeneity and treatment resistance in cancer. Increasing evidence shows that glioblastoma (GBM) cells display prominent intrinsic plasticity and reversibly adapt to dynamic microenvironmental conditions. Limited genetic evolution at recurrence further suggests that resistance mechanisms also largely operate at the phenotypic level. Here we review recent literature underpinning the role of GBM plasticity in creating gradients of heterogeneous cells including those that carry cancer stem cell (CSC) properties. A historical perspective from the hierarchical to the nonhierarchical concept of CSCs towards the recent appreciation of GBM plasticity is provided. Cellular states interact dynamically with each other and with the surrounding brain to shape a flexible tumor ecosystem, which enables swift adaptation to external pressure including treatment. We present the key components regulating intra-tumoral phenotypic heterogeneity and the equilibrium of phenotypic states, including genetic, epigenetic, and microenvironmental factors. We further discuss plasticity in the context of intrinsic tumor resistance, where a variable balance between preexisting resistant cells and adaptive persisters leads to reversible adaptation upon treatment. Innovative efforts targeting regulators of plasticity and mechanisms of state transitions towards treatment-resistant states are needed to restrict the adaptive capacities of GBM.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Ecosistema , Glioblastoma/genética , Glioblastoma/patología , Humanos , Células Madre Neoplásicas/patología
10.
Malays Orthop J ; 16(3): 139-142, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36589377

RESUMEN

Solitary plasmacytoma (SPC) account for only 5% of plasma cell neoplasms, and the literature hardly reports spinal SPC with a neurological deficit. Furthermore, spinal surgical intervention during pregnancy is rarely encountered and often requires multidisciplinary collaboration and management. The objective of this case report is to highlight this near-miss diagnosis and spinal surgical intervention during pregnancy. A 31-year-old woman with 24 weeks gestation presented with sudden paralysis and incontinence, with an underlying history of chronic backpain over a two-month period. Initially, she was treated for musculoskeletal back pain by obstetric colleagues during an antenatal visit, and no radiograph was performed. A non-contrasted spinal MRI was eventually requested when she started to show bilateral lower limb weakness, numbness and incontinence. The MRI highlighted thoracic vertebrae T11 vertebra plana with kyphotic deformity and a paraspinal soft tissue mass compressing the spinal cord causing spinal cord oedema. Our initial working diagnosis was spinal tuberculosis (TB), considering TB is highly endemic in Malaysia. However, TB workup was negative, and we proceeded with spinal surgery and transpedicular biopsy. Neurology improved significantly after surgery. Eventually, serum protein electrophoresis reported plasma dyscrasia, and HPE confirmed plasmacytoma. The patient was referred to a haematologist for steroidal and chemotherapy treatment.

11.
STAR Protoc ; 2(2): 100534, 2021 06 18.
Artículo en Inglés | MEDLINE | ID: mdl-34027491

RESUMEN

Tumor organoids and patient-derived orthotopic xenografts (PDOXs) are some of the most valuable pre-clinical tools in cancer research. In this protocol, we describe efficient derivation of organoids and PDOX models from glioma patient tumors. We provide detailed steps for organoid culture, intracranial implantation, and detection of tumors in the brain. We further present technical adjustments for standardized functional assays and drug testing. For complete details on the use and execution of this protocol, please refer to Golebiewska et al. (2020).


Asunto(s)
Neoplasias Encefálicas/patología , Ensayos de Selección de Medicamentos Antitumorales/métodos , Glioma/patología , Xenoinjertos , Organoides , Animales , Antineoplásicos/farmacología , Técnicas de Cultivo de Célula , Femenino , Xenoinjertos/citología , Xenoinjertos/efectos de los fármacos , Humanos , Masculino , Ratones , Organoides/citología , Organoides/efectos de los fármacos , Células Tumorales Cultivadas/citología
12.
Ann Ib Postgrad Med ; 19(Suppl 1): 90-99, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35095360

RESUMEN

INTRODUCTION: Kaduna State is among the three States with the highest number of confirmed COVID-19 cases. The objective of this study was to assess the knowledge, risk perception and practices of staff towards prevention and control of COVID-19 infection in schools to provide policy makers, education and health managers required information to manage the epidemic as the schools prepare to re-open. METHODS: This was a school-based survey conducted using purposive sampling of 55 schools located in nine LGAs with the highest number of reported COVID-19 cases as at October 2020. Five schools with the highest students'/pupils' enrollment in each of the LGA were selected and all staff were interviewed. Information on knowledge, risk perception and practices of prevention was collected. Descriptive statistics were generated using Stata v14 software. RESULTS: A total of 1065 staff in 55 schools completed the interview. Major sources of information are television (73%), radio (61%), and social media (57%); and 76% indicated that a virus is the causative agent of COVID-19. Overall, 70%, 19%, 7%, 9.3% and 0% respectively had adequate knowledge of cause, preventive measures, respiratory hygiene, modes of transmission and symptoms of COVID-19; however only 14% ever attended a workshop on COVID-19. Eighty-two percent and 89% respectively believed in the efficacy of face masks and handwashing as means of prevention; 39% thought that they are likely to contract COVID-19. Ninety-nine percent and 90% have ever used face mask and hand sanitizer to prevent COVID-19; 96% and 85% respectively have use these methods in previous 24hours. Between 42% and 73% of schools needed additional commodities/requirements/supplies to comply fully with COVID-19 prevention protocols. CONCLUSION: While knowledge of COVID-19 is suboptimal, perception is positive and practice is high. Thus, teachers need to be well informed and encouraged to sustain current levels of preventive measures. Government needs to provide schools with adequate preventive commodities to ensure compliance.

13.
Acta Neuropathol ; 140(6): 919-949, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33009951

RESUMEN

Patient-based cancer models are essential tools for studying tumor biology and for the assessment of drug responses in a translational context. We report the establishment a large cohort of unique organoids and patient-derived orthotopic xenografts (PDOX) of various glioma subtypes, including gliomas with mutations in IDH1, and paired longitudinal PDOX from primary and recurrent tumors of the same patient. We show that glioma PDOXs enable long-term propagation of patient tumors and represent clinically relevant patient avatars that retain histopathological, genetic, epigenetic, and transcriptomic features of parental tumors. We find no evidence of mouse-specific clonal evolution in glioma PDOXs. Our cohort captures individual molecular genotypes for precision medicine including mutations in IDH1, ATRX, TP53, MDM2/4, amplification of EGFR, PDGFRA, MET, CDK4/6, MDM2/4, and deletion of CDKN2A/B, PTCH, and PTEN. Matched longitudinal PDOX recapitulate the limited genetic evolution of gliomas observed in patients following treatment. At the histological level, we observe increased vascularization in the rat host as compared to mice. PDOX-derived standardized glioma organoids are amenable to high-throughput drug screens that can be validated in mice. We show clinically relevant responses to temozolomide (TMZ) and to targeted treatments, such as EGFR and CDK4/6 inhibitors in (epi)genetically defined subgroups, according to MGMT promoter and EGFR/CDK status, respectively. Dianhydrogalactitol (VAL-083), a promising bifunctional alkylating agent in the current clinical trial, displayed high therapeutic efficacy, and was able to overcome TMZ resistance in glioblastoma. Our work underscores the clinical relevance of glioma organoids and PDOX models for translational research and personalized treatment studies and represents a unique publicly available resource for precision oncology.


Asunto(s)
Neoplasias Encefálicas/tratamiento farmacológico , Glioma/tratamiento farmacológico , Xenoinjertos/inmunología , Organoides/patología , Temozolomida/uso terapéutico , Animales , Neoplasias Encefálicas/genética , Glioblastoma/tratamiento farmacológico , Glioblastoma/genética , Glioma/genética , Xenoinjertos/efectos de los fármacos , Humanos , Ratones , Recurrencia Local de Neoplasia/genética , Organoides/inmunología , Medicina de Precisión/métodos , Ratas
14.
Malays J Pathol ; 42(2): 301-305, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32860387

RESUMEN

INTRODUCTION: Yolk sac tumour (YST) or endodermal sinus tumour is rare and typically seen in gonads. CASE REPORT: We described a case of extragonadal vaginal YST in a one year and seven months old girl who presented with vaginal discharge and bleeding, and discuss its differential diagnosis and potential pitfalls in immunohistochemistry. She was found to have a suprapubic mass on examination. The serum alpha fetoprotein was 11919.4 ng/mL. Computed tomography of the pelvis revealed a large 6.4 cm heterogenous pelvic mass. Colposcopic examination of the pelvis showed a fungating vaginal mass that was subsequently confirmed as a yolk sac tumour. Immunohistochemically, the malignant cells were positive toward CKAE1/AE3, AFP and glypican-3, as well as CD117. DISCUSSION: Solid pattern extragonadal vaginal YST may morphologically resemble dysgerminoma that is also CD117 positive, while the glandular pattern YST may have clear cytoplasm and is positive for cytokeratin; hence, may resemble clear cell carcinoma. Being mindful of these potential diagnostic caveats is necessary to prevent misdiagnosis.


Asunto(s)
Tumor del Seno Endodérmico , Neoplasias Vaginales , Biomarcadores de Tumor/metabolismo , Diagnóstico Diferencial , Disgerminoma/diagnóstico , Tumor del Seno Endodérmico/diagnóstico , Tumor del Seno Endodérmico/patología , Femenino , Humanos , Inmunohistoquímica , Lactante , Proteínas Proto-Oncogénicas c-kit/metabolismo , Sarcoma de Células Claras/diagnóstico , Vagina/patología , Neoplasias Vaginales/diagnóstico , Neoplasias Vaginales/patología
15.
Malays J Pathol ; 41(1): 59-63, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31025640

RESUMEN

Alpha-fetoprotein (AFP)-producing carcinoma which microscopically mimics hepatocellular carcinoma (HCC) is a rare entity known as hepatoid adenocarcinoma (HC). They usually arise in the stomach, while oesophageal origin is only occasionally encountered. This tumour is highly aggressive and is associated with a poor prognosis. They frequently metastasise to the liver, thus giving rise to diagnostic difficulty, especially in cases where simultaneous oesophageal and liver mass are present. We reported a case of oesophageal hepatoid carcinoma with multiple liver metastasis, that was associated with an increased serum AFP. The distinction between HCC and HC is important because HC is more aggressive and has a poorer prognosis with limited therapeutic options. An extensive diagnostic work-up which include a thorough clinical history, radiological investigations (computed tomography or magnetic resonance imaging) as well as tissue biopsy supported by a panel of immunohistochemical markers are necessary to aid in the diagnosis of HC.


Asunto(s)
Adenocarcinoma/diagnóstico , Adenocarcinoma/secundario , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patología , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundario , Adulto , Carcinoma Hepatocelular/diagnóstico , Diagnóstico Diferencial , Humanos , Masculino , alfa-Fetoproteínas/análisis
16.
Malays J Pathol ; 41(3): 293-301, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31901914

RESUMEN

INTRODUCTION: Thyroid carcinoma is classically diagnosed based on certain histological criteria. In some cases, definitive diagnoses may be challenging when morphological features are equivocal. This study evaluated the usefulness of Cytokeratin 19 (CK 19) as an immunohistochemical marker to differentiate the different histological types of malignant thyroid neoplasms, particularly papillary thyroid carcinoma (PTC) from benign thyroid lesions. MATERIALS AND METHODS: We collected 54 malignant and 65 benign thyroid lesions diagnosed by histology in Universiti Kebangsaan Malaysia Medical Centre between January 2010 and December 2015. All cases were immunohistochemically stained with CK 19 and evaluated by 3 independent observers. The immunostaining patterns were scored based on the intensity and proportion of staining and finally graded as negative, weak positive, moderate positive or strong positive. In addition, the immunostaining scores of the malignant cases were correlated with their TNM pathological tumour stages. RESULTS: Cytokeratin 19 staining expression was higher in malignant than benign thyroid lesions (p < 0.001) which was most prominent among classical PTC. The four PTC cases that showed negative or weak staining were all follicular variant of PTC. Benign conditions were mostly negative or showed weak positivity. There was no correlation between CK 19 expression and TNM primary tumour stage (pT). CONCLUSION: Cytokeratin 19 is a useful marker in differentiating malignant from benign thyroid conditions particularly the classical PTC, provided its interpretation is by correlation with morphology and takes into consideration the intensity and proportion of positive staining.


Asunto(s)
Queratina-19/metabolismo , Cáncer Papilar Tiroideo/patología , Glándula Tiroides/patología , Neoplasias de la Tiroides/patología , Adulto , Anciano , Biomarcadores de Tumor/metabolismo , Carcinoma Papilar/metabolismo , Carcinoma Papilar/patología , Diagnóstico Diferencial , Femenino , Humanos , Inmunohistoquímica/métodos , Malasia , Masculino , Persona de Mediana Edad , Cáncer Papilar Tiroideo/metabolismo , Glándula Tiroides/metabolismo , Neoplasias de la Tiroides/metabolismo
17.
Niger J Physiol Sci ; 34(2): 159-165, 2019 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-32343267

RESUMEN

This work investigated 30 skulls of the Kuri cattle comprising 15 males and 15 females, of three age groups, 10 young (9 months to less than 3 years), 10 middle aged (3 to 5 years) and 10 aged (greater than 5 years). The skulls were prepared using hot water maceration technique. Using Ruler, thread and divider; 59 Osteometric parameters were taken to determine sexual dimorphism, only 6 indices showed statistically significant differences between the sexes. These indices were maximum intercondylar width (MICW), right supraorbital foramen to interfrontal suture (ISRSOF), left supraorbital foramen to interfrontal suture (ISLSOF), lateral intercornual length (LICL), intertemporal line width (ITLW) and horn base circumference (HBC). The female had longer viscerocranial length (VCrL) both on the nasal and palatal aspects, but were wider in the male. The male had longer and wider neurocranium. The paracondylar process length (PCPL) was longer in the female, but the male had wider interparacondylar width (IPCW) and maximum intercondylar width (MICW) While the ISRSOF significant difference appeared only at the middle-age group at p<0.05, the ISLSOF did not differ significantly at any particular age group but only overall mean of all the three age groups (n=15) presented the difference significantly. The MICW showed significant difference (p<0.05) at two age groups; young and the middle-age. The LICL and ITLW values are highly significant (p<0.01) and the HBC value was also significant (p<0.05) all at the middle age. No significant difference was recorded between the two sexes in the aged Kuri cattle; indicating that the female tends to progressively increase in size beyond 5 years old thereby making these values insignificant from the male counterpart at old age. In conclusion, the middle-age Kuri cattle have the most sexually dimorphic osteometric landmarks in the skull with the male having higher values than the female. This data will be useful for anatomical, developmental, anthropological forensic and clinical studies, and form basis for comparison with other breeds of cattle.


Asunto(s)
Bovinos/anatomía & histología , Cráneo/anatomía & histología , Factores de Edad , Animales , Biometría , Femenino , Masculino , Valores de Referencia , Caracteres Sexuales
18.
J Epidemiol Glob Health ; 8(1-2): 91-100, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30859794

RESUMEN

Zaria is the educational hub of northern Nigeria. It is a developing city with a pollution level high enough to be ranked amongst the World Health Organization's (WHO) most polluted cities. The study appraised the influence of outdoor air pollution on the respiratory well-being of a population in a limited resource environment. With the approved ethics, the techniques utilized were: portable pollutant monitors, respiratory health records, WHO AirQ+ software, and the American Thoracic Society (ATS) questionnaire. They were utilized to acquire day-time weighted outdoor pollution levels, health respiratory cases, assumed baseline incidence (BI), and exposure respiratory symptoms among selected study participants respectively. The study revealed an average respiratory illness incidence rate of 607 per 100,000 cases. Findings showed that an average of 2648 cases could have been avoided if the theoretical WHO threshold limit for the particulate matter with diameter of <2.5/10 micron (PM2.5/PM10) were adhered to. Using the questionnaire survey, phlegm was identified as the predominant respiratory symptom. A regression analysis showed that the criteria pollutant PM2.5, was the most predominant cause of respiratory symptoms among interviewed respondents. The study logistics revealed that outdoor pollution is significantly associated with respiratory well-being of the study population in Zaria, Nigeria.


Asunto(s)
Contaminantes Atmosféricos/efectos adversos , Contaminación del Aire/efectos adversos , Material Particulado/análisis , Enfermedades Respiratorias/epidemiología , Población Urbana , Adulto , Estudios Transversales , Países en Desarrollo , Exposición a Riesgos Ambientales/análisis , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Nigeria , Calidad de Vida , Enfermedades Respiratorias/etiología , Enfermedades Respiratorias/fisiopatología , Estudios Retrospectivos , Medición de Riesgo , Estaciones del Año , Factores Socioeconómicos
19.
Folia Morphol (Warsz) ; 74(2): 183-7, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26050804

RESUMEN

This work investigated and analysed some morphometrical measurements of mandibles and maxillofacial regions of ten adult Kuri cattle (above 5 years) skulls that were apparently free from musculoskeletal deformity. A total of 19 (13 mandibular and 6 maxillofacial) parameters were taken. The mean mandibular length and height were found to be 41.3 ± 2.35 cm and 22.6 ± 1.40 cm, while the mean mental foramen height and width were 0.8 ± 0.08 cm and 1.5 ± 0.25 cm, respectively. The mean distances from lateral alveolar root to mental foramen and from the latter to the most caudal border of the mandible were 4.8 ± 0.61 cm and 34.2 ± 1.93 cm, respectively. The mean mandibular foramen width was 1.1 ± 0.14 cm, while the distance from this foramen to the caudal border of mandible at that level was 4.0 ± 0.32 cm. The mean distances from facial tuberoses to the infraorbital foramen and from the latter to the alveolar root ventral to it were 5.3 ± 0.63 cm and 3.7 ± 0.47 cm, whereas the mean infraorbital foramen height and width stood at 1.2 ± 0.18 cm and 1.0 ± 0.22 cm, respectively. The infraorbital foramens in 60% of the specimen were located above the first upper premolar, while 20% were above second premolar, and another 20% at the junction above first and second upper premolars. These findings provide important landmarks needed for clinical manoeuvres on the head of the Kuri cattle for regional anaesthesia in procedures like trephination, dehorning, tooth extraction and oral and dental surgeries.

20.
Folia Morphol (Warsz) ; 74(2): 188-91, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26050805

RESUMEN

The purpose of this study was to examine the morphometry of the foramen magnum of African four-toed hedgehog (Atelerix albiventris) in Maiduguri. Fourteen hedgehog skulls (7 male and 7 female each) were used for this study. The overall mean value of foramen magnum height and width were 0.51 ± 0.05 cm and 0.64 ± 0.04 cm while occipital condylar and interparacondylar widths were 1.00 ± 0.12 cm and 1.62 ± 0.07 cm, respectively. There was no significant difference between the two sexes. The foramen magnum index was 83.4 ± 5.51 cm in males and was significantly higher than 76.3 ± 6.37 cm observed in females. The presences of dorsal notches (occipital dysplasia) were observed, that were of three distinct types. It is envisaged, that the study will provide a valuable database on the anatomy of foramen magnum of hedgehogs in Nigeria for morphological, neurological, zooarchaeological, and comparative anatomical studies.

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