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1.
Ultrasonics ; 141: 107343, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38754149

RESUMEN

Nomex honeycomb composite (NHC) has been increasingly used in the automotive, aerospace and defence applications due to its excellent thermal and mechanical properties. Its complex cellular hexagonal thin-walled configuration along with heterogeneous, soft and brittle nature pose substantial processing defects such as burr formation, tearing of walls, surface roughness, dimensional inaccuracy and low machining quality during conventional machining (CM). These surface defects have a substantial influence on the operating life and functional performance of its sandwiched structural members. Hybrid ultrasonic vibration assisted machining (HUSVAM) technology has been introduced to overcome such limitations. For an in depth research on HUSVAM of NHC using ultrasonic toothed disc cutter (UTDC), three dimensional finite element model was developed and experimental validation was carried out. The numerical simulation and experimental results were found to be in good agreement with one another. The influence of various machining parameters including the ultrasonic tool vibration amplitude (UTVA), feed rate (FR), depth of cut (DoC) and spindle angular speed (SAS) on NHC cutting forces, chip formation and surface quality was investigated using both HUSVAM and CM techniques. Furthermore, stresses, deformation and forces near tool-workpiece interaction along with the surface topography and morphologies were also analysed and compared for various operating conditions. A reduction in the cutting forces was found with the increase of SAS and UTVA (up to 65.47 % and 65.74 %, respectively). Although, the cutting forces were observed to increase by increasing the DoC and FR (up to 159.45 % and 126.33 %, respectively). DoC has a greater impact on the cutting forces among all machining parameters according to 4 levels, 4 factors (L16) orthogonal experiments based on Taguchi method. The results show that the chip formation and machining quality of NHC core can be improved with HUSVAM technique using UTDC. HUSVAM also reduced the cutting forces (up to 73 %) compared to CM. The ultrasonic toothed disc cutter generated large number of burr with very short length, no tearing defects and no uncut fibers as observed from scanning electron microscopy of NHC hexagonal cell structure, walls and triple points. A burr formation of less than 10 % was realized during HUSVAM of NHC cores for Fx≤3N, while it was found up to 20 % if Fx>3N, compared to at least 40 % during CM. The finite element model developed can be used to investigate the influence of HUSVAM on modern difficult to machine materials for enhanced surface quality.

3.
Int J Mol Sci ; 25(1)2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38203743

RESUMEN

High-grade gliomas are extremely fatal tumors, marked by severe hypoxia and therapeutic resistance. Autophagy is a cellular degradative process that can be activated by hypoxia, ultimately resulting in tumor advancement and chemo-resistance. Our study aimed to examine the link between autophagy markers' expression in low-grade gliomas (LGGs) and high-grade gliomas (HGGs). In 39 glioma cases, we assessed the protein expression of autophagy markers LC3B, SQSTM1/p62, and DRAM by immunohistochemistry (IHC) and the mRNA expression of the autophagy genes PTEN, PI3K, AKT, mTOR, ULK1, ULK2, UVRAG, Beclin 1, and VPS34 using RT-qPCR. LC3B, SQSTM1/p62, and DRAM expression were positive in 64.1%, 51.3%, and 28.2% of glioma cases, respectively. The expression of LC3B and SQSTM1/p62 was notably higher in HGGs compared to LGGs. VPS34 exhibited a significant differential expression, displaying increased fold change in HGGs compared to LGGs. Additionally, it exhibited robust positive associations with Beclin1 (rs = 0.768), UVRAG (rs = 0.802), and ULK2 (rs = 0.786) in HGGs. This underscores a potential association between autophagy and the progression of gliomas. We provide preliminary data for the functional analysis of autophagy using a cell culture model and to identify potential targets for therapeutic interventions.


Asunto(s)
Genes Reguladores , Glioma , Humanos , Proteína Sequestosoma-1/genética , Glioma/genética , Autofagia/genética , Beclina-1/genética , Hipoxia
4.
J Coll Physicians Surg Pak ; 33(3): 297-302, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36945160

RESUMEN

OBJECTIVE: To compare clinical and biochemical characteristics of hospitalised COVID-19 patients and risk assessment of disease outcomes Study Design: Descriptive study. Place and Duration of the Study: Department of Pathology, Dow International Medical College and Sindh Infectious Diseases Hospital and Research Centre, from January to March 2022 Methodology: SARS CoV-2 PCR-positive hospitalised patients were enrolled. Delta or omicron variants infected patients were followed till the last recorded event of hospitalisation. After a detailed history, clinical and biochemical profiles were recorded during the hospitalisation. Length of hospitalisation, ICU admission and in-hospital mortality were taken as outcomes and odd ratios were calculated. RESULTS: During the study period, omicron was the predominant SARS CoV-2 variant. Omicron-infected patient were older (67 vs. 62 years) and had a significantly shorter duration between appearance of symptoms and hospitalisation (5 vs. 8 days), when compared with the delta patients. Median values of LDH, ferritin and TLC were significantly higher in delta patients (p<0.05). Delta infected patients have a 3.9 times more risk of prolonged hospital stay. In patients with increased TLC, the risk of prolonged hospitalisation and ICU admission was found 16% and 23%, respectively. However, the aOR for ICU admission and in- Hospital mortality were not found significant for the delta and omicron-infected patients. CONCLUSION: The clinical course and biochemical profiles are diverse in delta and omicron patients. Hospitalised patients with omicron infection exhibit shorter stays. High values of TLC are found associated with an increased risk of longer hospital stay and ICU admissions. KEY WORDS: COVID-19, Delta variant, Omicron variant, Hospitalised patients, Outcomes, In-hospital mortality, Biochemical markers, Clinical severity.


Asunto(s)
COVID-19 , Humanos , SARS-CoV-2 , Hospitalización , Medición de Riesgo
5.
Int J Mol Sci ; 24(2)2023 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-36675138

RESUMEN

Oral squamous cell carcinomas (OSCC) remain a major healthcare burden in Asian countries. In Pakistan alone, it is the most common cancer in males and second only to breast cancer in females. Alarmingly, treatment options for OSCC remain limited. With this context, investigations made to explore the inflammatory milieu of OSCC become highly relevant, with the hope of practicing immunotherapeutic approaches to address this highly prevalent tumor. We investigated the newly identified innate lymphoid cells (ILCs) and associated cytokines in well-defined human oral squamous cell carcinoma (OSCC) as well as in a 7,12-dimethylbenz[a]anthracene (DMBA)-induced murine model of OSCC using flow cytometry and quantitative real-time polymerase chain reaction (qPCR). We further went on to explore molecular circuitry involved in OSCC by developing a murine model of OSCC and using an α-Thy1 antibody to inhibit ILCs. Amongst the ILCs that we found in human OSCC, ILC3 (23%) was the most abundant, followed by ILC2 (17%) and ILC1 (1%). Mice were divided into four groups: DMBA (n = 33), DMBA+antibody (Ab) (n = 30), acetone (n = 5), and control (n = 5). In murine OSCC tissues, ILC1 and ILC3 were down-infiltrated, while ILC2 remained unchanged compared to controls. Interestingly, compared to the controls (DMBA group), mice treated with the α-Thy1 antibody showed fewer numbers of large tumors, and a larger percentage of these mice were tumor-free at this study's end point. We present novel data on the differential expansion/downsizing of ILCs in OSCC, which provides a pivotal basis to dive deeper into molecular circuitry and the OSCC tumor niche to devise novel diagnostic, therapeutic, and prognostic strategies to prevent/treat oral cancers.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Masculino , Femenino , Humanos , Ratones , Animales , Inmunidad Innata , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas de Cabeza y Cuello , Linfocitos , Modelos Animales de Enfermedad , Neoplasias de la Boca/patología , Pakistán
6.
Front Psychol ; 13: 955145, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36324782

RESUMEN

The aim of this study was to examine the importance of information technology for logistics Small Medium Entreprise (SMEs) in Pakistan. It is the time of technological rapidness; especially after COVID-19, the word business has majorly transformed into a digital business. If an organization did not shift toward technology, it would be hard for it to even sustain in this rapid era. This study adopts the questionnaire after extensive literature review. A quantitative study was conducted among logistics SMEs in Pakistan to empirically verify what competitive advantages they are leading and gaining from information technology and how much information technology is important for their sustainability. The literature lacks information about the ways in which information technology has been integrated into logistics SMEs operating model, and more specifically, there is no information about IT valence, IT resource commitment, IT managerial commitment, and IT competency. The research is primarily quantitative in nature, where the data were collected via a close-ended questionnaire from 340 logistics SMEs in Pakistan. The independent variable of this research was information technology (i.e., IT valence, IT resource commitment, IT managerial commitment, and IT competency), whereas the dependent variable was competitive advantage. The study found that IT had a significant impact on the competitive advantage of logistics SMEs operating in Pakistan. All the variables related to IT had a significant impact on competitive advantage, which included IT valence, IT resource commitment, IT managerial commitment, and IT competency. This study helps managers and owners of logistics SMEs in decision-making, who can understand how much IT can enhance their performance and reduce their risks. This study has been specifically conducted with logistics SMEs operating in Pakistan, which means that there is much scope to be worked upon, i.e., by selecting companies operating in other countries and comparing them with current findings. This study observes the impact of information technology (i.e., IT valence, IT resource commitment, IT managerial commitment, and IT competency) on competitive advantage, and other independent variables can be studied to find the impact on competitive advantage.

7.
Pak J Med Sci ; 38(7): 1857-1863, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36246670

RESUMEN

Background and Objective: Pakistan has witnessed a dramatic change in the increasing prevalence and emergence of HIV subtypes for more than two decades. Pakistani population is increasingly engaged in high-risk practices, and the prescribed drugs are potentially causing resistance. There are chances that these resistant strains are beginning to circulate from high-risk to the general population. Methods: The study was conducted at the section of Molecular Pathology Lab of Dow Diagnostic and Research Laboratory, Dow University of Health Sciences (DUHS) Karachi. In this study, we analyzed gene sequences of HIV for drug resistance and molecular epidemiology., along with amino acid sequence variability. Furthermore, we undertook phylogenetic analysis for possible geographic linkages of Pakistani HIV strains. Results: Our results demonstrate that A1 is the leading HIV subtype circulating in the country, whereas other emerging subtypes and recombinant forms, including subtype B, CRF02_AG, CRF10_CD CRF35_AD, and CRF11_cpx were also observed. Our sequences cluster with the Middle East, African, and a few European sequences according to geographical distribution. These sequences showed high-level resistance per drug resistance pattern, with 62.5% of patients exhibiting resistance to NNRTI drugs and 60% mutation at E138A and K103N, respectively, against NNRTI drugs. About 75% sequences showed resistance mutation at M184V against NRTI drugs. The antiretroviral drugs are now causing H-LR to the patients with no effect. Our results also revealed that certain regions of RT exhibited high sequence variability, especially at Amino Acids positions p.119, p.130, p.157, p.164. Conclusion: We hereby report major novel mutations and several minor mutations that may have a drastic change in the drug resistance pattern.

8.
BMC Cancer ; 22(1): 990, 2022 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-36115941

RESUMEN

BACKGROUND: A group of genetically altered cells that have not transformed into a clinical or histologically identifiable state of malignancy but contains a higher risk of transforming into one is known as the field of cancerization. Numerous molecules are being investigated for their significance in the development of this phenomenon. One such protein of this family is Kaiso also known as ZBTB33 (Zinc Finger and BTB Domain containing 33). This protein belongs to the POZ-ZF family of transcription factors and may have functional tasks similar to its other siblings such as the growth and development of vertebrates and the pathogenesis of neoplastic diseases. Nevertheless, its role in the pathogenesis, progression, epithelial mesenchyal transition and field cancerization in case of oral cancer still needs exploration. Hence, this study was designed to explore the expressional differences between the mucosa of controls and those diagnosed with oral squamous cell carcinoma (OSCC). METHODS: Soft tissue samples were obtained from the main tumor, tumor periphery and opposite buccal mucosa of 50 oral cancer patients, whereas normal mucosa was taken from 50 volunteers undergoing elective tooth removal. The acquired samples were subjected to Immunohistochemical exploration for expression of Kaiso and E-Cadherin. The expression was measured using Image-J IHC profiler and summed as Optical density. The Optical density values were then subjected to statistical analysis. RESULTS: Results revealed a significant differential expression of Kaiso between the mucosal tissues taken from oral cancer patients and controls (p-value: < 0.0001), showing almost 50% down-regulation of Kaiso in all three tissue samples taken from oral cancer patients as compared to normal mucosa. CONCLUSION: Kaiso has a significant difference of expression in the mucosa of oral cancer patients as compared to the mucosa of normal patients, making it a probable contributor to disease pathogenesis and field cancerization.


Asunto(s)
Transformación Celular Neoplásica , Neoplasias de la Boca , Carcinoma de Células Escamosas de Cabeza y Cuello , Factores de Transcripción , Cadherinas/biosíntesis , Cadherinas/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/patología , Humanos , Mucosa Bucal/metabolismo , Neoplasias de la Boca/genética , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Factores de Transcripción/biosíntesis , Factores de Transcripción/genética
9.
Ecancermedicalscience ; 16: 1413, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36072235

RESUMEN

Oral squamous cell carcinoma (OSCC) is the most common cancer in Pakistani men and the second most common cancer in women. The objective of our study was to devise a novel accelerated murine model of oral carcinogenesis that can be exploited as a tool to investigate the cancer circuitry involved in OSCC and to identify molecules of diagnostic, therapeutic and prognostic significance. A total of 40 healthy male, 6-8 weeks old, 22 ± 2 gram, Naval Medical Research Institute (NMRI) outbred strain mice were recruited in the experiment. NMRI mice are commonly used for animal experiments in various fields of biology and for drug toxicity. Of these, 25 mice underwent the oral carcinogenesis regimen via topical application of 0.5% 9,10-dimethyl-1,2-benzanthracene (DMBA) on the lower left lip for a maximum of 20 weeks and 15 mice were used as controls (without the carcinogenic regimen). Exophytic tissue masses were harvested, fixed in 10% formalin and stained with haematoxylin and eosin (H&E) for microscopic diagnosis. Additionally, the expression levels of CK 5/6, p53 and Ki-67 were investigated using immunohistochemistry. Of the 25 mice which underwent the carcinogenic regimen, 21 developed moderately differentiated squamous cell carcinoma and 1 showed dysplastic features with foci of invasion. Three mice were found dead with lesion(s). CK 5/6 showed strong positivity (100%) and p53 and Ki-67 showed patchy (<30%) strong positivity in OSCC, suggesting the similarity of our model to human OSCC. We present an accelerated, close-to-human carcinogenesis, model of oral carcinogenesis using DMBA in NMRI mice that can be exploited to study the pathogenesis of oral squamous cell carcinoma and subsequently devise immunotherapy or targeted therapy.

10.
Front Psychol ; 13: 772028, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35222183

RESUMEN

Social interactions through social commerce platforms empower consumers to share their personal experiences with others, but its role becomes more significant for societal protection during COVID-19. Numerous scholars have studied e-commerce extensively, but there is a lack of studies to identify social commerce characteristics to attract potential consumers during COVID-19. This study aims to examine the role of social commerce constructs by integrating social presence as a moderator in the model to explain consumers online shopping intentions in a Pakistani context, where lack of trust on the reliability and validity of comments from other consumers being considered the growing concern toward the success of social commerce. The quantitative data were collected from the respondents living in different cities of Pakistan. Most of the hypothesis supported and demonstrate the positive response from the Pakistani consumers having experience in shopping through social commerce platforms. The findings of this study will help scholars and managers to understand the attitude of Pakistani consumers.

11.
Asian Pac J Cancer Prev ; 22(12): 3735-3740, 2022 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-34973682

RESUMEN

The journal of APJCP (Asian Pacific Journal of Cancer Prevention) focuses to gather relevant and up-to-date novel information's related to cancer sciences. The research methodologies and approaches adopted by the researcher are prone to variation which may be desirable in the context of novel scientific findings however, the reproducibility for these studies needs to be unified and assured. The reproducibility issues are highly concerned when preclinical studies are reported in cancer, for natural products in particular. The natural products and medicinal plants are prone to a wide variation in terms of phytochemistry and phyto-pharmacology, ultimately affecting the end results for cancer studies. Hence the need for specific guidelines to adopt a best-practice in cancer research are utmost essential. The current AIMRDA guidelines aims to develop a consensus-based tool in order to enhance the quality and assure the reproducibility of studies reporting natural products in cancer prevention. A core working committee of the experts developed an initial draft for the guidelines where more focus was kept for the inclusion of specific items not covered in previous published tools. The initial draft was peer-reviewed, experts-views provided, and improved by a scientific committee comprising of field research experts, editorial experts of different journals, and academics working in different organization worldwide. The feedback from continuous online meetings, mail communications, and webinars resulted a final draft in the shape of a checklist tool, covering the best practices related to the field of natural products research in cancer prevention and treatment. It is mandatory for the authors to read and follow the AIMRDA tool, and be aware of the good-practices to be followed in cancer research prior to any submission to APJCP. Though the tool is developed based on experts in the field, it needs to be further updated and validated in practice via implementation in the field.


Asunto(s)
Antineoplásicos , Productos Biológicos , Políticas Editoriales , Revisión por Pares/normas , Proyectos de Investigación/normas , Consenso , Humanos , Reproducibilidad de los Resultados
12.
Pak J Med Sci ; 37(3): 858-862, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34104178

RESUMEN

OBJECTIVES: To investigate immune cell densities in tumor microenvironment of hepatocellular carcinoma. METHODS: This cross-sectional study was conducted during 2017-2019 at the Dow University of Health Sciences Karachi. A total of 42 subsequent patients undergoing liver biopsy/resection and diagnosed with hepatocellular carcinoma were included in the study. Moreover, a total of 10 control tissues were also included. In order to investigate immune cells densities in hepatocellular carcinoma, immunohistochemistry was performed using antibodies including α-MPO(neutrophils), α-CD-68(macrophages), α-CD-3(T-cells), α-CD-20(B-cells), α-CD-4(CD4+ T-cells) and α-CD-8(CD8+ T-cells). Quantification of immune cells/mm2 was performed as per the College of American Pathologists' guidelines. Data were analyzed using SPSS version 21. A p-value of 0.05 was considered significant at all times. RESULTS: We report significantly increased infiltration of macrophages (mean macrophages= 306.57/mm2, p-value <0.05), moderately significant infiltration of neutrophils (p-value=0.06) and B-cells (p-value=0.07) while no significant infiltration of CD4+T-cells (p- value=0.31), and CD8+T-cells (p-value=0.39) in tumour microenvironment of patients with hepatocellular carcinoma. CONCLUSION: We provide evidence for increased macrophage infiltration in liver cancer microenvironment suggesting a potential role of these cells in hepatocarcinogenesis.

13.
Pak J Med Sci ; 37(2): 582-587, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33679954

RESUMEN

In order to investigate the current status of skin cancer research output in Pakistan, International (PubMed) and national (PakMediNet) scientific databases were searched using variety of keywords to retrieve relevant publications. A strict inclusion criterion was applied to select skin cancer publications for final analyses. Data were recorded by two authors and consistent data were entered into SPSS and Microsoft Excel and analyzed for annual growth rate and frequencies. Of 116 articles that were finally included in the study, 74 were original articles, 24 were case-reports, 10 were review articles, three were editorials, two were research communications and one each of case-series, correspondence and response to letter to the editor. The first article on skin cancer from Pakistan was published in 1976 whereas the last article included in our study was published in December 2018. Excluding Karachi, most of the cities have no contribution in the field of skin cancer. Since 1976 to date, the average number of publications per year has been low, with only 2.7 publications per year. Skin cancer research is alarmingly scarce in Pakistan. This calls for immediate attention by all concerned to contribute and devise appropriate measures towards skin cancer research in Pakistan.

14.
15.
Environ Sci Pollut Res Int ; 28(21): 26449-26460, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33483931

RESUMEN

Environmental degradation has severely affected the natural cycle of ecosystem. It's high time now and humans should execute strategies effectively to protect the further degradation. Initially, we need to understand the ways that might affect the environment. Thus, existing research is designed to explore the nonlinear association between financial development (FD) and carbon dioxide emissions (CO2) in the context of low-income countries by employing the yearly data of 1990-2016. The panel smooth transition regression model (PSTR) is applied, and the result confirmed that the nexus between the two variables are nonlinear. Moreover, it also shows that at a low regime, FD increases the CO2 emissions but as the economy of low-income states progress to the high regime, the association between the two variables becomes negative and significant. The study also confirms that FD can reduce CO2 emissions once it reaches a certain threshold point. Based on these findings, new insights are provided for the policymakers, and several policies are suggested to improve the environmental quality in low-income countries.


Asunto(s)
Desarrollo Económico , Ecosistema , Dióxido de Carbono , Comercio , Humanos , Internacionalidad
16.
Environ Sci Pollut Res Int ; 28(2): 1426-1442, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32840747

RESUMEN

The study aims to analyze two objectives: first is to explore the non-linear relationship between tourism development, economic growth, urbanization, and environmental degradation, and also to analyze the threshold level of the contribution of tourism development on environmental degradation in top tourist arrival destinations. We applied the newly proposed econometric method panel smooth transition regression (PSTR) framework with two regimes on yearly panel data from 1995 to 2017. Findings suggest that the relationship between tourism development and environmental degradation is non-linear and regime dependent. Furthermore, the findings indicated that the relationship above the threshold level is negative and significant, while below the threshold, tourism development is positive and significant effect on environmental degradation. Tourism development and environmental degradation also exhibit the inverted U-shape relationship meaning that at a particular point, increase in tourism development increases in environmental degradation but after a particular point, increase in tourism development decreases the environmental degradation. The economic growth and urbanization also portray a non-linear and regime-dependent relationship with environmental degradation. The study assists policies and empirical information.


Asunto(s)
Desarrollo Económico , Urbanización , Dióxido de Carbono , Políticas , Turismo
17.
Environ Sci Pollut Res Int ; 28(11): 13323-13339, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33175351

RESUMEN

The study intends to explore the following objectives: initially, to examine the non-linear connection between globalization, renewable energy consumption, and environmental degradation. Secondly, to evaluate the role of globalization in increasing or decreasing the carbon emission at the threshold level for different income countries. Panel smooth transition regression (PSTR) is an econometric technique that has been applied for estimation utilizing the data from 1995 to 2017. Results signify that the globalization and environmental degradation have non-linear connection and depends on different regimes. Moreover, on the basis of estimation, it is considered that the effect beyond the threshold level can be damaging, whereas less than the threshold level globalization is positively related to carbon emission. Hence, the inverted U-shaped relation denotes that at a specific level, the rise in globalization reduces carbon emission, but later, a specific level globalization accumulates carbon emission. Carbon emission has non-linear and regime-dependent relation to economic development and renewable energy consumption. The study provides recommendations that can assist policymakers.


Asunto(s)
Dióxido de Carbono , Energía Renovable , Carbono , Desarrollo Económico , Internacionalidad
18.
Asian Pac J Cancer Prev ; 21(11): 3199-3209, 2020 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-33247676

RESUMEN

BACKGROUND: Role of TC2N in carcinogenesis has been largely unfathomed until recently when it was identified as a novel oncogene in lung cancer. Subsequently, a tumour suppressor role of TC2N was reported in breast cancer. It is therefore highly relevant to investigate TC2N molecular partners/mechanisms on a larger scale including a wider range of tumour types. METHODS: We investigated TC2N mRNA expression, its promoter methylation levels, effects of TC2N transcription on overall patient survival, somatic mutations in TC2N gene and correlation between TC2N mRNA expression and other cancer genes in pan-cancer by using data available from the Cancer Genome Atlas (TCGA) and the Genotype Tissue Expression (GTEx) databases. RESULTS: TC2N mRNA expression was differentially regulated in 9/33 TCGA tumour types. Of these 9 tumours, 5 tumour types (cholangiocarcinoma, ovarian-serous-cystadenocarcinoma, rectal-adenocarcinoma, stomach-adenocarcinoma and thymoma) had significantly higher TC2N mRNA expression while 4 (pheochromocytoma-and-paraganglioma, skin-cutaneous-melanoma, thyroid-carcinoma and uterine-carcinosarcoma) had significantly lower TC2N mRNA expression compared to matched and normal controls. TC2N promoter was hypermethylated in most cancers while hypomethylated in head-and-neck-squamous-cell-carcinoma and kidney-renal-clear-cell carcinoma. TC2N transcription was positively correlated with transcription of several other cancer genes including genes from Myc, cell-cycle, Nrf2, Wnt, PI3K, Hippo, Notch, TGFß and RAS/RTK pathways. Poor prognosis was associated with higher TC2N mRNA levels in pancreatic-adenocarcinoma and brain-lower-grade-glioma and lower TC2N mRNA levels in kidney-renal-clear-cell-carcinoma, mesothelioma, sarcoma and skin-cutaneous melanoma. Functional protein partners of TC2N were identified as STX2, SMEK1, SMEK2, STXBP5, SCARA5, MMRN1, CATSPER2, CATSPERB, CLEC4M and STAB2. Many of these proteins are key players in carcinogenesis of various cancers. Highest pathogenic somatic mutation rates in TC2N were found in skin-cutaneous-melanoma, uterine-corpus-endometrial-carcinoma, colon-endocervical-adenocarcinoma, bladder-urothelial-carcinoma and breast-invasive-carcinoma. CONCLUSION: Our findings unravel several un-explored avenues related to the role of TC2N in tumourigenesis of several cancers, suggesting TC2N as an important player and a potential candidate for tumour-therapy.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinogénesis/patología , Metilación de ADN , Regulación Neoplásica de la Expresión Génica , Neoplasias/patología , Proteínas Nucleares/metabolismo , Oncogenes , Biomarcadores de Tumor/genética , Carcinogénesis/genética , Carcinogénesis/metabolismo , Perfilación de la Expresión Génica , Humanos , Neoplasias/genética , Proteínas Nucleares/genética
19.
Asian Pac J Cancer Prev ; 21(11): 3251-3258, 2020 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-33247682

RESUMEN

OBJECTIVES: To estimate the cancer incidence by age group and gender for the population of Karachi Division by analyzing the Karachi Cancer Registry data of 2017-19. SETTINGS: The population of Karachi division is 16.1 million according to national census 2017. 'Karachi Cancer Registry' which is a part of 'National Cancer Registry' is collecting data from eight major hospitals in Karachi since 2017. For outcome measures, cancer counts and the age standardized incidence rates (ASIR) per 100,000 population were computed for age groups (0-14, 15-19 and ≥20 years), in both genders and all cancer site/type. METHODS: The population denominators were based on the population of Karachi division estimated at 16.1 million in the population census, 2017. Counts and age-standardized incidence rates (ASIR) were calculated for each of the three age categories. RESULTS: From Jan 2017 till Dec 2019 a total of 33,309 malignant cases were recorded in KCR database comprising 17,490 (52.5%) females and 15,819 (47.5%) males. ASIRs in age groups 0-14, 15-19 and ≥ 20 years, among female were 11.5, 2.4 and 223.6 and in males were 17.6, 3.2 and 216.7 respectively. The commonest diagnosis in children, adolescent and adults were (1) among females: children; bone (3.12),  leukemia (2.09) brain/CNS (1.26); in adolescents: bone (0.78), brain/CNS (0.27), connective and soft tissue (0.11), in adults: breast cancer (76.07), oral cancer (16.68) and ovary (10.89) respectively, and (2) among males: children; bone (4.56),  leukemia (2.79) and brain/CNS (1.88); in adolescent; bone (1.19), brain/CNS (0.31) and leukemia (0.21) and in adults: oral cancer (42.83), liver (16.10) and bone (13.37) respectively. CONCLUSION: Oral Cancer, a largely preventable cancer is the leading cancer in Karachi adult males while in female adults Breast Cancer is the leading cancer followed by Oral Cancer. In children and adolescents Bone, Leukemia and Brain/CNS malignancies are most common.
.


Asunto(s)
Bases de Datos Factuales/estadística & datos numéricos , Neoplasias/epidemiología , Adolescente , Adulto , Factores de Edad , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Pakistán/epidemiología , Pronóstico , Factores Sexuales , Adulto Joven
20.
Pak J Med Sci ; 36(7): 1572-1578, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33235577

RESUMEN

OBJECTIVES: To present 2010-2019 cancer data from the Dow Cancer Registry representing all districts of Karachi (~17.4 million). METHODS: The study was conducted at the Dow University of Health Sciences. After ethical approval, the Dow Cancer Registry was established at the largest government-run diagnostic and reference center of Karachi (Dow Labs). All cancers registered during 2010-2019 were analyzed. Patients >18years of age were labeled as adults while those with ages ≤18years were classified as children/young adults. RESULTS: During 2010-2019, a total of 22,858 cancers were registered. Of these, 9,112(39.9%) cancers were diagnosed in males while 13,746(60.1%) in females. Incidence rates for all cancers (all ages) were 108/1,00,000 for males and 188.6/1,00,000 for females. In adult males, cancer of lip and oral cavity was the most frequently diagnosed cancer (33.6%), followed by non-melanoma -skin-cancer (NMSC) (7.2%), oesophagus (6.8%), colorectum (6.7%) and stomach (4.9%). In adult females, breast cancer was the most frequently recorded malignancy (53.2%), followed by cancers of lip and oral cavity (10.4%), oesophagus (5.3%), colorectum (3.3%) and NMSC (3%). In children, most common malignancy was that of brain and nervous system (15.3%), followed by Hodgkin's lymphoma (14.2%), colorectum (8.1%), endocrine-&-related organs (8%) and non-Hodgkin's lymphoma (7.8%). CONCLUSION: Cancers of lip and oral cavity and breast cancer were the most common malignancies in males and females respectively. In paediatric group, cancers of brain and nervous system were most common. Alarmingly, Karachi males have highest ASR of cancers of lip and oral cavity compared to any other city of Pakistan.

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