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1.
Medicina (Kaunas) ; 60(4)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38674306

RESUMO

Background and Objectives: Human papillomavirus (HPV) was previously investigated in lung cancer with wide inter-geographic discrepancies. p16INK4a has been used as a surrogate for detecting high-risk HPV (HR-HPV) in some cancer types. This study assessed the evidence of HPV in non-small-cell lung cancer (NSCLC) among Jordanian patients, investigated the expression of p16INK4a, and evaluated its prognostic value and association with HPV status. Materials and Methods: The archived samples of 100 patients were used. HPV DNA detection was performed by real-time polymerase chain reaction (RT-PCR). p16INK4a expression was assessed by immunohistochemistry (IHC). The Eighth American Joint Committee on Cancer protocol (AJCC) of head and neck cancer criteria were applied to evaluate p16INK4a positivity considering a moderate/strong nuclear/cytoplasmic expression intensity with a distribution in ≥75% of cells as positive. Results: HPV DNA was detected in 5% of NSCLC cases. Three positive cases showed HR-HPV subtypes (16, 18, 52), and two cases showed the probable HR-HPV 26 subtype. p16INK4a expression was positive in 20 (20%) NSCLC cases. None of the HPV-positive tumors were positive for p16INK4a expression. A statistically significant association was identified between p16INK4a expression and the pathological stage (p = 0.029) but not with other variables. No survival impact of p16INK4a expression was detected in NSCLC cases as a group; however, it showed a statistically significant association with overall survival (OS) in squamous cell carcinoma (SqCC) cases (p = 0.033). Conclusions: This is the first study to assess HPV and p16INK4a expression in a Jordanian population. HPV positivity is rare in NSCLC among a Jordanian subpopulation. P16 INK4a reliability as a surrogate marker for HPV infection in lung cancer must be revisited.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Inibidor p16 de Quinase Dependente de Ciclina , Neoplasias Pulmonares , Infecções por Papillomavirus , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/virologia , Inibidor p16 de Quinase Dependente de Ciclina/genética , DNA Viral/análise , Papillomavirus Humano , Imuno-Histoquímica , Jordânia/epidemiologia , Neoplasias Pulmonares/virologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real
2.
J Med Virol ; 95(11): e29250, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-38009250

RESUMO

Cytomegalovirus (CMV) is the most prevalent infection in recipients of hematopoietic stem cell transplant (HSCT). QuantiFERON-CMV (QF-CMV) and QuantiFERON-Monitor (QFM) assays were used to test whether immune-competent adult allogeneic HSCT recipients with CMV-specific T cells can control CMV infection or reactivation. Our data demonstrated a significant correlation between CMV infection measured by CMV-antigenemia test and QF-CMV results, graft versus host disease (GvHD), and mortality rates. The QF-CMV test revealed that CMV-specific T cells with higher interferon-γ (IFN-γ) release were correlated with lower CMV infection rates. There was a significant negative association between QF-CMV results, GvHD, and mortality rates. Data showed that a one-unit rise in IFN-γ was linked with a 12.7% reduction in GvHD and a 20.7% reduction in the mortality odds ratio. In addition, a negative correlation was found between QF-M results and CMV infection, with the QFM test predicting protection against CMV infection by 1.9%. This is one of the few studies establishing the QF-CMV test's predictive value for GvHD and mortality, its use to monitor HSCT patients for pre-emptive therapy, and the use of the QFM test to predict CMV infection and mortality in HSCT patients. Thus, these assays could be utilized to optimize preventive and pre-emptive therapy procedures to reduce transplant recipient adverse effects and posttransplant therapy costs.


Assuntos
Infecções por Citomegalovirus , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Adulto , Humanos , Citomegalovirus , Transplantados , Infecções por Citomegalovirus/prevenção & controle , Interferon gama , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos
3.
Clin Lab ; 68(4)2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35443604

RESUMO

BACKGROUND: The introduction of checkpoint inhibitors in solid cancer therapy showed successful results. The role of Programmed Death-1/Programmed Death-Ligand 1 (PD1/PD-L1) in hematologic malignancies is currently being investigated and clinical trials are ongoing. Preliminary findings showed conflicting results. In this study, we examined the degree of PD-L1 and PD-L2 expression in primary acute leukemia patients. METHODS: Flow cytometry expression of PD-L1 and PD-L2 was evaluated in de novo acute leukemia in the collaborating institutions between 2018 - 2020. RESULTS: One hundred forty patients were identified. PD-L1 was positive in 34/70 (49%) of AML, 25/50 (50%) of B-ALL, and none (0/20) of T-ALL patients. In contrast, PD-L2 was solely expressed in eight (19%) AML patients. The expression of PD-L1 showed statistically significant correlation with the type of acute leukemia (AML and B-ALL > T-ALL, p < 0.001) and with age group (adults > children, p = 0.048), but not with blast count, immunophenotype or cytogenetic mutations. The positivity for PD-L1 was associated with worse overall survival in AML, but not in B-ALL. CONCLUSIONS: The expression of PD-L1 is common among newly diagnosed AML and B-ALL patients and is not restricted to relapsed cases as previously described. PD-L2 is less commonly expressed and is accompanied by PD-L1 expression. Positive PD-L1 patients may benefit from treatment with immune checkpoint inhibitors, especially in AML. Further studies are recommended.


Assuntos
Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Doença Aguda , Adulto , Antígeno B7-H1 , Criança , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética
4.
Breast Cancer Res Treat ; 185(2): 459-467, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32974788

RESUMO

PURPOSE: Breast cancer that overexpresses the human epidermal growth factor receptor-2 (HER2) and both estrogen (ER) and progesterone (PR) receptors is recently recognized as a subtype (triple-positive) with distinctive behavior and response to treatment. In this study, we investigate the treatment outcomes and the beneficial effect of anti-HER2 treatment in relation to level of hormone-receptor (HR) expression. METHODS: Consecutive breast cancer patients with triple-positive disease, diagnosed, treated and followed at our institution between 2006 and 2016 were enrolled. Disease-free survival (DFS) was studied in relation to the level of HR-positivity. RESULTS: During the study period, a total of 312 were enrolled; median age (range) was 47 (20-83) years. Fifty (16.0%) of the enrolled patients received adjuvant chemotherapy without trastuzumab (cohort A). All remaining patients were treated with both chemotherapy and trastuzumab and were divided into two groups: Cohort B with both ER and PR scores ≥ 50% (n = 130, 41.7%) and Cohort C with ER and/or PR < 50% (n = 132, 42.3%). After a median follow-up of 47 months, 14 (28.0%), 30 (23.1%) and 20 (15.2%) patients in cohorts A, B, and C had an event in a form of local/system relapse or death while disease-free. The estimated 5-year DFS was 56.2%, 75.4%, and 80.8%, respectively, and at 7 year was 56.2%, 67.1%, and 78.0%, respectively (p < 0.001). CONCLUSIONS: HER2-positive tumors are not homogeneous; stronger ER/PR co-expression may weaken the beneficial effect of anti-HER2 therapy. Such findings may have potential implication on modifying anti-HER2 treatment based on the strength of HR expression.


Assuntos
Neoplasias da Mama , Receptor ErbB-2 , Receptores de Progesterona , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Feminino , Hormônios , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/genética , Resultado do Tratamento
5.
BMC Infect Dis ; 21(1): 508, 2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059011

RESUMO

BACKGROUND: Hepatitis B and C infections and transmission are a serious challenge to all healthcare systems. We studied seroprevalence rates of Transfusion Transmitted Diseases (TTD) among blood bank donors in Jordan from 2014 to 2019 as a follow-up study of our previously published work. In addition, we wanted to explore the efficacy of the mandatory vaccination of infants against hepatitis B virus (HBV) which was implemented by the Ministry of Health since 1995 for the eradication of HBV infection in Jordan. METHODS: We reviewed blood bank donors' records at King Hussein Cancer Center (KHCC) from January 1st, 2014, until December 31st, 2019. Results of seropositivity prevalence rates for HBsAg, anti-HBcore, and anti-HCV, using Enzyme-Linked ImmunoSorbent Assay (ELISA) were compared to seropositivity rates from our previously published data. In addition, our results were compared to data obtained from other blood banks in Jordan, as well as compared to published information from blood banks in neighboring countries. RESULTS: The prevalence rates (%) of seropositive blood donors for viral hepatitis for the years 2014, 2015, 2016, 2017, 2018, and 2019, were as follows: HBsAg rates were 0.3386, 0.2108, 0.1801, 0.1898, 0.2068, and 0.2741; anti-HBcore rates were 4.1112, 3.2271, 2.9748, 2.8405, 2.6879 and 3.0986; and anti-HCV rates were 0.1129, 0.0486, 0.0548, 0.0654, 0.0782, and 0.0839, respectively. There was a significant increase in the prevalence of HBsAg, Anti-HBcore and Anti-HCV antibodies in 2019 (one sample z-score test, p < 0.00001). CONCLUSIONS: Prevalence rates of hepatitis B and C infections among Jordanian blood bank donors showed a steady decline between 2009 and 2017, and these rates were much lower in Jordan than in neighboring countries. However, an increase in the prevalence rates of hepatitis B and C infections among blood bank donors was documented in 2019. While the reasons for this increase are not clear yet, these findings highlight the importance of renewed efforts to increase public health awareness of HBV and implement effective measures to prevent the transmission and infection with HBV, including national vaccination programs.


Assuntos
Doadores de Sangue/estatística & dados numéricos , Reação Transfusional/epidemiologia , Bancos de Sangue/estatística & dados numéricos , Hepacivirus/imunologia , Hepacivirus/isolamento & purificação , Hepatite B/diagnóstico , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/isolamento & purificação , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Hepatite C/prevenção & controle , Anticorpos Anti-Hepatite C/sangue , Humanos , Jordânia/epidemiologia , Prevalência , Estudos Soroepidemiológicos , Reação Transfusional/sangue , Reação Transfusional/prevenção & controle , Reação Transfusional/virologia , Vacinas contra Hepatite Viral/administração & dosagem
6.
Ann Diagn Pathol ; 51: 151703, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33454500

RESUMO

Triple negative breast cancer (TNBC) represents a small subtype of breast cancer yet it has the worst outcome. Immunotherapy using immune checkpoint inhibitors combined with chemotherapy was recently approved by the FDA raising the hope for an improved outcome. The approval was based on demonstration of a positive PD-L1 expression using the SP142 CDx assay 1. We aimed to study a cohort of TNBC patients in terms of prevalence of the PD-L1 expression using the approved assay and to investigate its association with clinicopathological variables. This is a single center retrospective study consisting of 49 TNBC patients who had available archived paraffin-embedded tissue blocks from the primary tumors. All blocks were stained using the SP142 CDx assay as per the manufacture's instruction. Clinicopathological data were collected from medical records. Eighteen of the 49 (36.7%) patients were found to have a score of 1% or more by the immune cell-scoring algorithm. PDL-1 expression was significantly associated with the degree of tumor infiltrating lymphocytes (TILs). No additional significant relationship was found between PD-L1 expression and any of the other investigated clinicopathological variables. Although a trend of favorable prognostic association with PD-L1 expression was noted. The overall and event free survival were significantly related to pathological response to neoadjuvant therapy. Conclusion: Our PD-L1 rate of 36.7% is close to the results of the previously reported 40.9% in the IMpassion 130 trial. There were no significant association between positive PD-L1 expression and clinicopathological variables however a trend of a favorable outcome was observed.


Assuntos
Antígeno B7-H1/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Antineoplásicos/uso terapêutico , Estudos de Coortes , Quimioterapia Combinada/métodos , Feminino , Expressão Gênica/genética , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Imuno-Histoquímica/métodos , Linfócitos do Interstício Tumoral/patologia , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias/métodos , Prevalência , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
7.
Ann Diagn Pathol ; 47: 151556, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32592992

RESUMO

Oncotype Dx (ODx) recurrence score (RS) is used in early breast cancer to guide the use of adjuvant therapy. In addition to RS the test produces results of reverse transcriptase-polymerase chain reaction (RT-PCR) of Estrogen receptors (ER), Progesterone receptors (PgR) and Human epidermal growth factor receptor 2 (HER2-neu). Our goal was to determine the correlation between immunohistochemistry (IHC) and RT-PCR testing of ER, PgR and HER2-neu and to correlate the results of ODx RS with tumors' grade, age and PgR status. 113 patients with ER+, HER2-neu- breast cancers that underwent ODx testing were analyzed for receptors correlation and concordance rates by the 2 methods. A total of 104 patients had ER+/PgR+ tumors and 9 patients had ER+/PgR- tumors by IHC, the average RS were 17.5 ± 9.1 and 31.2 ± 8.7 (P < 0.001) respectively. The Spearman correlation coefficient between IHC and ODx results were 0.5 (95% CI 0.34-0.62) for ER and 0.78 (95% CI 0.7-0.84) for PgR. The concordance rate between IHC and ODx was 98.2% for ER, 89.4%.for PgR and 99.1% for HER2-neu. Most of the discordant cases (9 out of 13) were low positive (1-10%) by IHC and negative by RT-PCR. In addition higher tumor grade was associated with a higher ODx RS. Our data show that the IHC results were highly concordant with RT-PCR for ER, PgR and Her2-neu. In addition low positive (1-10%) ER/PgR might indicate a real negative status. Our study shows that ER+/PgR- breast cancers are associated with a significantly higher ODx RS.


Assuntos
Neoplasias da Mama/patologia , Recidiva Local de Neoplasia/genética , Receptor ErbB-2/genética , Receptores de Estrogênio/genética , Receptores de Progesterona/genética , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Feminino , Humanos , Imuno-Histoquímica/métodos , Imuno-Histoquímica/estatística & dados numéricos , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/estatística & dados numéricos
8.
Ann Diagn Pathol ; 40: 72-76, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31075666

RESUMO

Primary mediastinal large B-cell lymphoma (PMBL) and classic Hodgkin lymphoma (CHL) are the most common large cell lymphomas arising in the mediastinum and are thought to be closely related histogenetically. Although the distinction between PMBL and CHL is usually straightforward, in some cases it is challenging and rarely these neoplasms have intermediate features and qualify for the diagnosis of mediastinal gray zone lymphoma (GZL). CD83 and fascin are markers of CHL and CD23 is a marker of PMBL. In this study we assess the utility of this combination of these immunohistochemical markers to distinguish CHL from PMBL. We retrospectively collected cases of PMBL, CHL and GZL from three centers. Tissue sections were stained with CD83, fascin and CD23. CD83 was expressed in the neoplastic cells of 100% of CHL (22/22), 93% of GZL (16/18) and 41% of PMBL (9/22). Similarly, fascin was positive in the neoplastic cells of 100% of CHL (22/22), 86% of GZL (18/21) and 32% of PMBL (7/22). CD23 was positive in 95% of PMBL (21/22), 67% of GZL (12/18) and 9% of CHL (2/22). CD83 and fascin are sensitive markers for CHL but not specific whereas CD23 is sensitive for PMBL and uncommon in CHL. The GZL cases in this study had an intermediate immunophenotype, but the results were closer to CHL than PMBL. A large panel of immunohistochemical studies is recommended to distinguish CHL from PMBL entities and we suggest that CD83, fascin and CD23 add value to panels designed for this differential diagnosis.


Assuntos
Biomarcadores Tumorais/metabolismo , Doença de Hodgkin/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Neoplasias do Mediastino/diagnóstico , Antígenos CD/metabolismo , Proteínas de Transporte/metabolismo , Diagnóstico Diferencial , Doença de Hodgkin/metabolismo , Doença de Hodgkin/patologia , Humanos , Imunoglobulinas/metabolismo , Imuno-Histoquímica , Imunofenotipagem , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Neoplasias do Mediastino/metabolismo , Neoplasias do Mediastino/patologia , Glicoproteínas de Membrana/metabolismo , Proteínas dos Microfilamentos/metabolismo , Receptores de IgE/metabolismo , Estudos Retrospectivos , Antígeno CD83
9.
Ann Diagn Pathol ; 39: 53-58, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30718223

RESUMO

The transmembrane receptor NOTCH1 is thought to be associated with the development and progression of T-acute lymphoblastic leukemia (T-ALL)/T-lymphoblastic lymphoma (T-LBL) and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). The current study aimed to characterize NOTCH1 expression and elucidate the variants in the functional PEST domain of the receptor in T-ALL/LBL and CLL/SLL. The nuclear expression of NOTCH1 protein was detected in 25% and 5% of cases of T-ALL/LBL and CLL/SLL, respectively, whereas cytoplasmic expression was detected in 33.3% and 15% cases, respectively. The frequency of variants in T-ALL/LBL was 33%, whereas 40% of CLL/SLL cases possessed variants. Four novel variants were identified; three of which were non-synonymous and one common variant c.7280_7280delG between T-ALL/LBL and CLL/SLL cases. The previously described variant, c.7541_7542delCT, was detected in 3 cases of CLL/SLL. These results provide support for the contribution of NOTCH1 in the etiology of these types of cancers.


Assuntos
Variação Genética , Leucemia Linfocítica Crônica de Células B/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Receptor Notch1/genética , Receptor Notch1/metabolismo , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Feminino , Predisposição Genética para Doença , Humanos , Jordânia , Masculino , Domínios Proteicos , Receptor Notch1/química
10.
Pediatr Blood Cancer ; 62(12): 2157-61, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26222068

RESUMO

BACKGROUND: KRAS and NRAS gene mutations are frequently observed in childhood leukemia. The objective of this study was to determine the frequency of RAS mutations and the association between RAS mutations and other genetic aberrations in Arab Asian children with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). METHODS: Diagnostic samples of 485 patients (<18 years) with acute leukemia from Iraq and Jordan were obtained, using Flinders Technology Associates filter papers. Polymerase chain reaction and direct sequencing were performed in Japan. RESULTS: RAS mutations were detected in 86/318 (27%) of ALL cases and 35/167 (21%) of AML cases. The frequency of NRAS mutation was similar to that of KRAS mutation in ALL. Two RAS mutations were detected in nine patients. Among 264 Iraqi patients with ALL, RAS mutation was significantly associated with lower initial white blood cell count. Of 57 patients with chimeric transcripts, only two patients with either TEL-AML1 or E2A-PBX1 had KRAS mutation. The frequency of NRAS mutation was four times higher than that of KRAS mutation in AML. FAB-M4 and M5 subsets were associated with RAS mutation. Among 134 Iraqi patients with AML, 18 patients had RAS mutations and other genetic aberrations. In particular, 9 of 25 (36%) with MLL-rearrangement had RAS mutations. CONCLUSION: The prevalence of oncogenic RAS mutations was higher among Arab Asian children than in other countries. RAS mutations in AML were found to coexist with other genetic aberrations, particularly MLL rearrangement.


Assuntos
GTP Fosfo-Hidrolases/genética , Leucemia Mieloide Aguda/genética , Proteínas de Membrana/genética , Taxa de Mutação , Mutação , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteínas Proto-Oncogênicas/genética , Proteínas ras/genética , Adolescente , Árabes , Povo Asiático , Criança , Pré-Escolar , Feminino , Histona-Lisina N-Metiltransferase , Humanos , Lactente , Iraque , Jordânia , Leucemia Mieloide Aguda/etnologia , Masculino , Proteína de Leucina Linfoide-Mieloide , Leucemia-Linfoma Linfoblástico de Células Precursoras/etnologia , Proteínas Proto-Oncogênicas p21(ras)
11.
Adv Exp Med Biol ; 864: 141-55, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26420619

RESUMO

King Hussein Cancer (KHCC) is a specialized cancer center that treats both adult and pediatric cancer patients from Jordan and the neighboring countries. KHCC is acknowledged as a leader in cancer treatment in the Middle East and its vision is to maintain its leading position in cancer therapy and research. Hence, KHCC embarked on establishing the first ISO compliant cancer biobank (KHCCBIO) in Jordan.Currently, there are very few biobanks in the Middle East, hence, KHCC wanted to change this situation by establishing an ISO-compliant cancer biobank which would incorporate all current international guidelines and best-in class practices under an approved quality management system for the benefit of researchers in Jordan, its neighboring countries, and throughout the world. The established biobank would follow the highest ethical standards in collecting, processing, storing and distributing high-quality, clinically annotated biospecimens.The strategy used in establishing KHCCBIO was based on taking advantage of international networking and collaboration. This in essence led to knowledge transfer between well established organizations, institutions and individuals from Europe and Jordan, in existing technological innovation and internationally recognized quality standards. KHCC efforts were facilitated by a grant from the European Union under the seventh frame work program.Future aims of KHCCBIO are to develop KHCC's research infrastructure, increase its scope and visibility and improve its competitiveness throughout the biomedical science arena. Moreover, KHCCBIO is aiming to establish a platform for future knowledge transfer and collaborative research; develop partnerships between European and Middle Eastern organizations.


Assuntos
Bancos de Espécimes Biológicos , Cooperação Internacional , Neoplasias/diagnóstico , Bancos de Espécimes Biológicos/economia , Bancos de Espécimes Biológicos/ética , Bancos de Espécimes Biológicos/normas , Pesquisa Biomédica , Humanos , Jordânia
12.
Pediatr Blood Cancer ; 61(12): 2313-5, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25110876

RESUMO

Individuals with biallelic truncating PRF1 mutations typically present with fulminant early-onset familial hemophagocytic lymphohistiocytosis (FHL). We report a 19-year-old male with a 5-year history of recurrent fever and headaches progressing to refractory seizures. Brain imaging revealed multiple ring enhancing lesions. Laboratory investigations demonstrated that the patient displayed defective lymphocyte cytotoxicity and carried a homozygous missense PRF1 mutation, c.394G > A (p.Gly132Arg). The patient was successfully treated with chemo-immunotherapy followed by matched related allogeneic hematopoietic stem cell transplantation (HSCT). Our findings demonstrate that prompt HSCT of late-onset FHL with primarily neurological manifestation can reverse central nervous system symptoms and improve long-term outcome.


Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Antineoplásicos/uso terapêutico , Encefalopatias/terapia , Transplante de Células-Tronco Hematopoéticas , Linfo-Histiocitose Hemofagocítica/complicações , Mutação/genética , Perforina/genética , Adolescente , Encefalopatias/etiologia , Terapia Combinada , Feminino , Humanos , Masculino , Prognóstico , Rituximab
13.
Pediatr Blood Cancer ; 61(11): 1980-5, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25066867

RESUMO

BACKGROUND: RUNX1 mutation plays an important role in adult leukemic transformation. However, its contribution to the development of childhood leukemia remains unclear. In the present study, we analyzed point mutations of RUNX1 gene in children and adolescents with acute myeloid leukemia (AML) from Iraq and Jordan. PROCEDURE: Bone marrow and/or peripheral blood samples were collected from 178 patients of Arab Asian ethnicity (aged ≤17 years) newly diagnosed with AML: 145 samples from Iraq and 33 samples from Jordan. Direct DNA sequencing was performed on six genes including RUNX1 gene (exons 3-8). RESULTS: RUNX1 point mutations were identified in 10 (5.6%) of 178 patients. One patient possessed biallelic mutations of RUNX1 gene. C-terminal area was the predominant site of RUNX1 mutations (eight in C-terminal and two in N-terminal). Patients with RUNX1 mutations were significantly older than those with wild-type of the gene. Additionally, AML M0 subtype was more frequently found in patients with RUNX1 mutations. Both RUNX1 mutations and RAS mutations were identified in 4 of 10 children. Three patients with RUNX1 mutation had FLT3-ITD. On the other hand, 36 (21.4%) and 25 (14.9%) of 168 patients with wild-type of the gene had a RAS mutation and FLT3-ITD, respectively. Eight of 10 patients with RUNX1 mutations died of hematological relapse. CONCLUSION: The incidence of RUNX1 mutations in Arab Asian children and adolescents with AML was 5.6%. Further studies are required to clarify whether RAS mutations contribute to the development of pediatric AML associated with RUNX1 mutations.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core/genética , Genes ras , Leucemia Mieloide Aguda/genética , Mutação , Adolescente , Árabes , Povo Asiático/genética , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Leucemia Mieloide Aguda/etnologia , Masculino , Mutação Puntual
14.
Acad Pathol ; 11(1): 100109, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38433775

RESUMO

Pathologists use certain terminologies to communicate uncertainty in pathology reports. The message conveyed in pathology reports may be interpreted differently by clinicians leading to possible miscommunication. We aimed to compare the interpretation and impact of uncertainty phrases between pathologists and clinicians. A survey with examples of uncertain diagnoses containing ("suspicious for", "indefinite for", "favor", "cannot exclude", "suggestive of", "compatible with", "cannot rule out", "highly suspicious for" and "consistent with") was sent to pathologists and clinicians. For each diagnosis, participants assigned a level of certainty from 1 to 10 and were asked whether they would recommend treatment based on such phraseology. Thirty-six responses (from 7 pathologists, 10 surgeons, 8 pediatric oncologists, 8 medical oncologists, 2 radiation oncologists and 1 diagnostic radiologist) were received. Pathologists had a narrower range of uncertainty compared to clinicians. Wide variation between both groups was seen for all phrases except "compatible with" and "highly suspicious for". 'Indefinite for' showed the lowest mean of certainty (4.67 for pathologists; 4.00 for clinicians) whereas 'consistent with' had the highest (8.83 for pathologists and 9.38 for clinicians). There was a significant difference in the degree of certainty between both groups for "compatible with" (7.83 for pathologists and 9.06 for clinicians, p = .009). For treatment decisions, pathologists and clinicians agreed on initiating treatment when "consistent with" and "compatible with" were used and gave variable responses for the other terms. They proposed opposing treatment recommendations for "favor". Pathologists and clinicians varied in interpretation of uncertainty phrases which may impact treatment.

15.
Technol Cancer Res Treat ; 23: 15330338241242635, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38562094

RESUMO

Background: One of the most frequently used methods for quantifying PD-L1 (programmed cell death-ligand 1) expression in tumor tissue is IHC (immunohistochemistry). This may predict the patient's response to anti-PD1/PD-L1 therapy in cancer. Methods: ImageJ software was used to score IHC-stained sections for PD-L1 and compare the results with the conventional manual method. Results: In diffuse large B cell lymphoma, no significant difference between the scores obtained by the conventional method and ImageJ scores obtained using the option "RGB" or "Brightness/Contrast." On the other hand, a significant difference was found between the conventional and HSB scoring methods. ImageJ faced some challenges in analyzing head and neck squamous cell carcinoma tissues because of tissue heterogenicity. A significant difference was found between the conventional and ImageJ scores using HSB or RGB but not with the "Brightness/Contrast" option. Scores obtained by ImageJ analysis after taking images using 20 × objective lens gave significantly higher readings compared to 40 × magnification. A significant difference between camera-captured images' scores and scanner whole slide images' scores was observed. Conclusion: ImageJ can be used to score homogeneous tissues. In the case of highly heterogeneous tissues, it is advised to use the conventional method rather than ImageJ scoring.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias de Cabeça e Pescoço , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Antígeno B7-H1/metabolismo , Projetos de Pesquisa , Ligantes , Biomarcadores Tumorais/análise
16.
J Int Med Res ; 52(6): 3000605241259747, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38902203

RESUMO

BACKGROUND: Breast cancer, particularly triple-negative breast cancer (TNBC), poses a significant global health burden. Chemotherapy was the mainstay treatment for TNBC patients until immunotherapy was introduced. Studies indicate a noteworthy prevalence (0.2% to 18.6%) of mismatch repair protein (MMRP) deficiency in TNBC, with recent research highlighting the potential of immunotherapy for MMRP-deficient metastatic breast cancer. This study aims to identify MMRP deficiency in TNBC patients using immunohistochemistry. METHODS: A retrospective cohort study design was used and included TNBC patients treated between 2015 and 2021 at King Hussein Cancer Center. Immunohistochemistry was conducted to assess MMRP expression. RESULTS: Among 152 patients, 14 (9.2%) exhibited deficient MMR (dMMR). Loss of PMS2 expression was observed in 13 patients, 5 of whom showed loss of MLH1 expression. Loss of MSH6 and MSH2 expression was observed in one patient. The median follow-up duration was 44 (3-102) months. Despite the higher survival rate (80.8%, 5 years) of dMMR patients than of proficient MMR patients (62.3%), overall survival did not significantly differ between the two groups. CONCLUSION: Approximately 9% of TNBC patients exhibit dMMR. dMMR could be used to predict outcomes and identify patients with TNBC who may benefit from immunotherapy.


Assuntos
Reparo de Erro de Pareamento de DNA , Proteínas de Ligação a DNA , Endonuclease PMS2 de Reparo de Erro de Pareamento , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Endonuclease PMS2 de Reparo de Erro de Pareamento/metabolismo , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Idoso , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteína 1 Homóloga a MutL/metabolismo , Proteína 1 Homóloga a MutL/genética , Proteína 2 Homóloga a MutS/metabolismo , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Taxa de Sobrevida , Imuno-Histoquímica , Idoso de 80 Anos ou mais , Prognóstico
17.
SAGE Open Med ; 12: 20503121241259340, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38855006

RESUMO

Background: Recruitment of low risk blood donors can be challenging. Efforts should be made to increase the level of awareness and positive attitude towards blood donation. An essential step to achieve this is obtaining comprehensive data about the current situation of awareness, knowledge and attitudes of the population towards blood donation. Methods/materials: The present study was conducted at two blood donation centres in Amman, Jordan, during 2021. A total of 536 whole blood donors were included. Data regarding their demographic characteristics, blood donation history as well as their knowledge and attitudes regarding blood donation were collected by a questionnaire. Results: Four hundred ninety participants (91.4%) were males, whereas only 46 participants (8.6%) were females. Ninety seven subjects (18.1%) were first time donors, whereas 431 subjects (81.9%) had previous donations. The participants' median score in the knowledge section was 19.0 points (range 5-25 points). Based on a cut-off of 15 out of 28: 84% of the participants were knowledgeable. Similarly 97% of the participants had a positive attitude based on a cut-off of 17 out of 32 points. Multivariate analysis revealed that high knowledge score was significantly associated with study major and employment status, whereas a positive attitude was significantly associated with a higher income. More than half of first time donors stated lack of awareness as being the reason for not donating blood before. Conclusion: Measures to improve awareness, knowledge and attitudes towards blood donation should be implemented in order to meet the increasing demand for blood and blood components. Targeted campaigns, correction of some misconceptions and using different motivations are suggested.

18.
Vaccines (Basel) ; 11(2)2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36851168

RESUMO

BACKGROUND: Anti-inflammatory corticosteroids are used in cancer treatment and COVID-19 infections. Data on the impact of non-dexamethasone corticosteroids on COVID-19 infection severity in cancer patients are minimal. This study investigates if corticosteroid treatment affects the disease severity in adult cancer patients. METHODS: A total of 116 COVID-19-infected cancer patients on hydrocortisone (H) or prednisone (P) were compared to 343 untreated patients. The study included patients who received corticosteroids before (B), after (A), or both before and after (B and A) COVID-19 infections. Ventilation support, hospitalization and mortality were investigated. RESULTS: Our data showed that a significantly greater number of patients taking H or P required ventilation support and hospitalization and that mortality rates were higher than the control group. Patients who received H or P after COVID-19 infection had a significantly worse prognosis than the other sub-groups and the control group. CONCLUSION: Corticosteroids impacted cancer patients' COVID-19 prognosis. Despite the limited sample size, H- and P-treated patients' corticosteroids performed worse than the control, especially if treatments were received after COVID-19 infection. Hence, when a cancer patient already on H or P treatment is diagnosed with COVID-19, we recommend switching to a steroid treatment as suggested by international guidelines.

19.
Int J Biol Markers ; 38(1): 53-60, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36617986

RESUMO

BACKGROUND: Programmed death-ligand 1 (PD-L1) expression in some tumors has prognostic implications. This work aims at investigating PD-L1 expression in diffuse large B-cell lymphoma (DLBCL) and to study its association with clinicopathological variables. METHODS: The study consisted of 75 DLBCL patients who were cared for at the King Hussein Cancer Center during the period 2015-2018. The expression of PD-L1 in tumor tissue was assessed by immunohistochemistry using the anti-human PD-L1 (Clone 22C3) monoclonal antibody. The correlation between gender, age, clinical stage, pre-treatment-LDH level, tumor location, response to therapy, overall and event-free survival with PD-L1 expression was studied. RESULTS: Six patients were excluded from further analysis as they were in relapse at the time of tissue sampling. The tumor proportion score (TPS) was ≥1% in 16/69 (23.2%) of DLBCL cases while the combined positive score (CPS) at a cut-off of ≥20 was observed in 23/69 (33.3%) cases. No significant difference in PD-L1 expression was found between germinal center B-cell-like (GCB) and non-GCB subtypes. Similarly, no differences in PD-L1 expression (at CPS ≥20 and TPS ≥1) were found between different genders, age groups, clinical stages, tumor location, and patient response to therapy. However, base-line lactate dehydrogenase was significantly elevated in patients with PD-L1 CPS ≥20. The overall survival was not significantly different between PD-L1-positive and -negative groups. On the other hand, the median event-free survival was higher in either of the PD-L1 TPS or CPS negative groups at 107months each versus 54 months in the PD-L1 positive group of either category. CONCLUSIONS: PD-L1 expression can predict event-free survival in DLBCL cases and therefore poor prognosis.


Assuntos
Antígeno B7-H1 , Linfoma Difuso de Grandes Células B , Humanos , Masculino , Feminino , Biomarcadores Tumorais/metabolismo , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/metabolismo , Prognóstico
20.
J Int Med Res ; 51(7): 3000605231187796, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37493465

RESUMO

Mixed sex cord-stromal tumors, which consist of poorly differentiated Sertoli cells and Leydig cells and juvenile granulosa cell tumor tissue, are extremely rare. Most of these tumors are unilateral and stage I at the time of diagnosis; nonetheless, according to the available relevant English-language literature, these tumors maintain a malignant potential. We herein report a case involving a 15-year-old girl diagnosed with a mixed sex cord-stromal tumor (gynandroblastoma with juvenile granulosa cell tumor component). Left salpingo-oophorectomy was initially performed, and the diagnosis of a juvenile granulosa cell tumor was established. Right salpingo-oophorectomy was performed 1 year later, at which time the specimen showed a different growth pattern involving epithelioid cells and tubules, resembling a Sertoli-Leydig cell tumor. Immunohistochemical staining was performed and the specimen was compared with that obtained 1 year earlier. We concluded that the tumors were linked and most likely constituted a gynandroblastoma (mixed form of sex cord-stromal tumor). Although this is an extremely uncommon ovarian tumor, it should be considered when diverse tumor morphology is identified. Bilateral metachronous involvement of the ovaries is possible. The grade of the Sertoli-Leydig cell component may influence the prognosis of such a tumor.


Assuntos
Tumor de Células da Granulosa , Neoplasias Ovarianas , Tumores do Estroma Gonadal e dos Cordões Sexuais , Masculino , Feminino , Humanos , Adolescente , Tumor de Células da Granulosa/cirurgia , Tumores do Estroma Gonadal e dos Cordões Sexuais/diagnóstico , Tumores do Estroma Gonadal e dos Cordões Sexuais/cirurgia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/patologia , Biomarcadores Tumorais
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