RESUMO
Acute monocytic leukemia is a type of myeloid leukemia that develops in monocytes. The current clinical therapies for leukemia are unsatisfactory due to their side effects and nonspecificity toward target cells. Some lectins display antitumor activity and may specifically recognize cancer cells by binding to carbohydrate structures on their surface. Therefore, this study evaluated the response of the human monocytic leukemia cell lines THP-1 to the Olneya tesota PF2 lectin. The induction of apoptosis and reactive oxygen species production in PF2-treated cells was evaluated by flow cytometry, and the lectin-THP-1â cell interaction and mitochondrial membrane potential were evaluated by confocal fluorescence microscopy. PF2 genotoxicity was evaluated by DNA fragmentation analysis via gel electrophoresis. The results showed that PF2 binds to THP-1 cells, triggers apoptosis and DNA degradation, changes the mitochondrial membrane potential, and increases reactive oxygen species levels in PF2-treated THP-1 cells. These results suggest the potential use of PF2 for developing alternative anticancer treatments with enhanced specificity.
Assuntos
Lectinas , Leucemia Monocítica Aguda , Humanos , Lectinas/farmacologia , Lectinas/metabolismo , Leucemia Monocítica Aguda/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Apoptose/fisiologia , Células THP-1RESUMO
PURPOSE: The US does not have universal paid family and medical leave. We examine the direct effects of access to paid leave on patient-reported health, quality of life (QOL), and perceived stress of employed patients who underwent bone marrow transplantation (BMT) to treat advanced blood cancer as well as the indirect effects through reductions in the financial burden (FB) that patients face. METHODS: Our cross-sectional observational study took place at three US transplantation centers in 2014 and 2015. All English-speaking cancer patients 6-month post-BMT were mailed a 43-item survey assessing financial situation, employer benefits, and patient-reported health outcomes. The sample includes the 171 respondents who were employed at the time of BMT. RESULTS: Seemingly unrelated regression analysis confirms that patient access to paid leave was associated with reductions in all three measures of FB, and lower levels of financial hardship were related with improved health, QOL, and perceived stress outcomes. For self-reported health and perceived stress outcomes, all of the effects of patient paid leave operate indirectly through reductions in FB. For QOL outcomes, there is both a direct effect (over 80%) of paid leave and an indirect effect through reduction of FB. CONCLUSION: We found that paid leave affected health outcomes for BMT patients mostly through alleviating FB. These findings suggest universal paid leave policies in the US might alleviate financial hardship and have positive effects on the self-reported QOL of employed patients facing intensive medical treatments.
Assuntos
Transplante de Medula Óssea/economia , Transplante de Medula Óssea/psicologia , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida/psicologia , Salários e Benefícios/economia , Adulto , Estudos Transversais , Emprego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Análise de Regressão , Salários e Benefícios/estatística & dados numéricos , Inquéritos e QuestionáriosRESUMO
Although hematopoietic cell transplantation (HCT) is the only curative therapy for many advanced hematologic cancers, little is known about the financial hardship experienced by HCT patients nor the association of hardship with patient-reported outcomes. We mailed a 43-item survey to adult patients approximately 180 days after their first autologous or allogeneic HCT at 3 high-volume centers. We assessed decreases in household income; difficulty with HCT-related costs, such as need to relocate or travel; and 2 types of hardship: hardship_1 (reporting 1 or 2 of the following: dissatisfaction with present finances, difficulty meeting monthly bill payments, or not having enough money at the end of the month) and "hardship_2" (reporting all 3). Patient-reported stress was measured with the Perceived Stress Scale-4, and 7-point scales were provided for perceptions of overall quality of life (QOL) and health. In total, 325 of 499 surveys (65.1%) were received. The median days since HCT was 173; 47% underwent an allogeneic HCT, 60% were male, 51% were > 60 years old, and 92% were white. Overall, 46% reported income decline after HCT, 56% reported hardship_1, and 15% reported hardship_2. In multivariable models controlling for income, those reporting difficulty paying for HCT-related costs were more likely to report financial hardship (odds ratio, 6.9; 95% confidence interval, 3.8 to 12.3). Hardship_1 was associated with QOL below the median (odds ratio, 2.9; 95% confidence interval, 1.7 to 4.9), health status below the median (odds ratio, 2.2; 95% confidence interval, 1.3 to 3.6), and stress above the median (odds ratio, 2.1; 95% confidence interval, 1.3 to 3.5). In this sizable cohort of HCT patients, financial hardship was prevalent and associated with worse QOL and higher levels of perceived stress. Interventions to address patient financial hardship-especially those that ameliorate HCT-specific costs-are likely to improve patient-reported outcomes.
Assuntos
Transplante de Células-Tronco Hematopoéticas/economia , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Custos e Análise de Custo , Feminino , Nível de Saúde , Transplante de Células-Tronco Hematopoéticas/psicologia , Humanos , Renda , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
<b><br>Introduction:</b> Despite advancements in diagnostic methods, the early detection of colorectal anastomotic leakage (CAL) continues to pose challenges. The identification of reliable markers is crucial to reduce patient morbidity and mortality. Cytokines present in drain fluid and systemic cytokine levels have shown promise as predictive markers for CAL; however, additional high-quality evidence is warranted to enhance the reliability and validity of the findings in this field.</br> <b><br>Aim:</b> This systematic review and meta-analysis aimed to assess the significance of peritoneal and serum/plasma interleukin-10 (IL-10) levels in the early detection of CAL in patients undergoing colorectal surgery for colorectal cancer.</br> <b><br>Methods:</b> A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science databases, covering studies published until July 2023. The search aimed to identify relevant studies investigating the levels of plasma/serum and peritoneal IL-10 (or both) in colorectal cancer patients undergoing colorectal surgery, specifically focusing on the presence of CAL. Data on the mean and standard deviation of IL-10 levels in both CAL and non-CAL patients were extracted from the selected studies. Mean differences in IL-10 levels were analyzed for each postoperative day (POD) using the OpenMeta [analyst] software.</br> <b><br>Results:</b> 11 articles were selected for inclusion in this systematic review. Among them, nine articles reported data on peritoneal IL-10 levels, while four articles focused on circulating IL-10 levels. The statistical analysis included four eligible articles that assessed peritoneal IL-10 levels, and the results indicated no significant increase in CAL patients compared to non-CAL patients on any postoperative day (POD). Meta-analysis for circulating IL-10 levels was not feasible.</br> <b><br>Conclusions:</b> Up to now, peritoneal and systemic IL-10 levels cannot be considered as early markers for CAL after colorectal surgery in colorectal cancer patients. More high-quality studies are needed to establish the potential of IL-10 as a reliable marker for detecting anastomotic leakage after colorectal surgery.</br>.
Assuntos
Neoplasias Colorretais , Interleucina-10 , Humanos , Fístula Anastomótica/diagnóstico , Fístula Anastomótica/etiologia , Reprodutibilidade dos Testes , Citocinas , Biomarcadores , Neoplasias Colorretais/cirurgiaRESUMO
Prohibitin (PHB) is a highly conserved eukaryotic protein complex involved in multiple cellular processes. In insects, PHB has been identified as a potential target protein to insecticidal molecules acting as a receptor of PF2 insecticidal lectin in the midgut of Zabrotes subfasciatus larvae (bean pest) and Cry protein of Bacillus thuringiensis in Leptinotarsa decemlineata (Colorado potato beetle). This study aimed to characterize the structural features of Z. subfasciatus prohibitin (ZsPHB) by homology modeling and evaluate its expression and tissue localization at different stages of larval development both at the transcript and protein levels. The samples were collected from eggs and larvae of different developmental stages. The immunodetection of ZsPHB was done with anti-PHB1 and confirmed by LC-MS/MS analysis. Gene expression analysis of ZsPHB1 and ZsPHB2 was performed by RT-qPCR, and immunohistochemistry with FITC-labeled anti-PHB1. Results showed that ZsPHBs exhibit distinctive characteristics of the SPFH protein superfamily. The transcript levels suggest a coordinated expression of ZsPHB1 and ZsPHB2 genes, while ZsPHB1 was detected in soluble protein extracts depending on the stage of development. Histological examination showed ZsPHB1 is present in all larval tissues, with an intense fluorescence signal observed at the gut. These results suggest a physiologically important role of PHB during Z. subfasciatus development and show its regulation occurs at the transcriptional and post-transcriptional levels. This is the first characterization of PHB in Z. subfasciatus.
Assuntos
Besouros , Fabaceae , Gorgulhos , Animais , Cromatografia Líquida , Besouros/genética , Larva/metabolismo , Proibitinas , Espectrometria de Massas em Tandem , Gorgulhos/genéticaRESUMO
RESUMEN La obstrucción intestinal inducida por íleo biliar es una condición rara pero significativa que se produce cuando una piedra en la vesícula se aloja en el tracto gastrointestinal. Entre los principales factores de riesgo para la obstrucción intestinal inducida por íleo biliar se encuentran la edad avanzada, el sexo femenino, la diabetes, los antecedentes de enfermedad biliar como cálculos biliares, así como procedimientos quirúrgicos previos relacionados con la vesícula biliar, como la colecistectomía. También el embarazo es un factor de riesgo conocido para la enfermedad de los cálculos biliares. En este artículo, se presenta el caso de una paciente de 38 años con antecedentes de tres cesáreas previas y sin comorbilidades aparentes. Antes de acudir al departamento de emergencias, la paciente experimentó dolor abdominal con cólico moderado en la parte inferior del abdomen durante dos días. El examen físico reveló sensibilidad abdominal difusa, predominantemente en la fosa ilíaca derecha, junto con signos de irritación peritoneal. Los análisis de laboratorio mostraron un recuento de leucocitos de 11 490 células/μl y una neutrofilia del 85,6 %. Después de una laparotomía exploratoria, se confirmó el diagnóstico sospechado de íleo biliar por cálculo. Se realizó una enterolitotomía y la paciente mostró un progreso posoperatorio favorable. En conclusión, es importante considerar la obstrucción intestinal inducida por íleo biliar en pacientes con síntomas relevantes y antecedentes médicos. Este reporte de caso subraya la importancia de considerar la obstrucción intestinal inducida por íleo biliar en pacientes con síntomas gastrointestinales y antecedentes de embarazo. El diagnóstico temprano y la intervención son cruciales para prevenir complicaciones graves.
ABSTRACT Gallstone ileus-induced intestinal obstruction is a rare but significant condition that occurs when a gallstone becomes lodged in the gastrointestinal tract. Major risk factors for gallstone ileus-induced intestinal obstruction include older age, female sex, diabetes, history of gallbladder disease such as gallstones, as well as previous gallbladder-related surgical procedures such as cholecystectomy. Pregnancy is also a known risk factor for gallstone disease. We present the case of a 38-year-old patient with a history of three cesarean sections and no apparent comorbidities. Prior to her visit to the emergency department, the patient experienced moderate colicky abdominal pain in the lower abdomen for two days. The physical examination revealed diffuse abdominal tenderness, predominantly in the right iliac fossa, along with signs of irritation of the peritoneum. Laboratory tests showed a leukocyte count of 11,490 cells/µl and neutrophilia of 85.6 %. Following an exploratory laparotomy, the suspected diagnosis of gallstone ileus was confirmed. An enterolithotomy was performed, and the patient experienced good post-surgical progress. In conclusion, it is important to consider gallstone ileus-induced intestinal obstruction among patients with relevant symptoms and medical history. This case report highlights the importance of considering gallstone ileus-induced intestinal obstruction among patients with gastrointestinal symptoms and a history of pregnancy. Early diagnosis and intervention are crucial to prevent serious complications.
RESUMO
Background: Financial hardship is a growing challenge for patients with blood cancer who undergo hematopoietic cell transplantation (HCT), and it is associated with poor patient-reported outcomes. In contrast, little is known about the potential impact of patient-reported financial hardship on post-HCT survival.Methods: We sought to describe the association of financial hardship with survival after HCT in a prospectively assembled cohort of patients from three large transplant centers (n = 325).Results: There was no association between financial hardship measures assessed at 6 months post-HCT and 1- or 2-year survival after HCT.Conclusions: Patient-reported financial distress after HCT does not seem to adversely affect post-HCT survival.Impact: When assessing the effectiveness of interventions to ameliorate familial financial burden among HCT, the focus should be on patient-reported outcomes rather than survival. Cancer Epidemiol Biomarkers Prev; 27(3); 345-7. ©2018 AACR.
Assuntos
Gastos em Saúde/estatística & dados numéricos , Neoplasias Hematológicas/mortalidade , Transplante de Células-Tronco Hematopoéticas/economia , Medidas de Resultados Relatados pelo Paciente , Fatores Socioeconômicos , Feminino , Neoplasias Hematológicas/economia , Neoplasias Hematológicas/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Autorrelato/economia , Autorrelato/estatística & dados numéricos , Análise de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: Hematologic cancers are associated with aggressive cancer-directed care near death and underuse of hospice and palliative care services. We sought to explore hematologic oncologists' perspectives and decision-making processes regarding end-of-life (EOL) care. METHODS: Between September 2013 and January 2014, 20 hematologic oncologists from the Dana-Farber/Harvard Cancer Center participated in four focus groups regarding EOL care for leukemia, lymphoma, multiple myeloma, and hematopoietic stem-cell transplantation. Focus groups employed a semistructured format with case vignettes and open-ended questions and were followed by thematic analysis. RESULTS: Many participants felt that identifying the EOL phase for patients with hematologic cancers was challenging as a result of the continuing potential for cure with advanced disease and the often rapid pace of decline near death. This difficulty was reported to result in later initiation of EOL care. Barriers to high-quality EOL care were also reported to be multifactorial, including unrealistic expectations from both physicians and patients, long-term patient-physician relationships resulting in difficulty conducting EOL discussions, and inadequacy of existing home-based EOL services. Participants also expressed concern that some EOL quality measures developed for solid tumors may be unacceptable for patients with blood cancers given their unique needs at the EOL (eg, palliative transfusions). CONCLUSION: Our analysis suggests that hematologic oncologists need better clinical markers for when to initiate EOL care. In addition, current quality measures may be inappropriate for identifying overly aggressive care for patients with blood cancers. Further research is needed to develop effective interventions to improve EOL care for this patient population.
Assuntos
Neoplasias Hematológicas/terapia , Oncologia , Padrões de Prática Médica , Assistência Terminal , Adulto , Idoso , Continuidade da Assistência ao Paciente , Feminino , Grupos Focais , Conhecimentos, Atitudes e Prática em Saúde , Cuidados Paliativos na Terminalidade da Vida , Humanos , Masculino , Pessoa de Meia-Idade , Transferência de Pacientes , Qualidade da Assistência à SaúdeRESUMO
A short G1 phase is a characteristic feature of mouse embryonic stem cells (ESCs). To determine if there is a causal relationship between G1 phase restriction and pluripotency, we made use of the Fluorescence Ubiquitination Cell Cycle Indicator (FUCCI) reporter system to FACS-sort ESCs in the different cell cycle phases. Hence, the G1 phase cells appeared to be more susceptible to differentiation, particularly when ESCs self-renewed in the naïve state of pluripotency. Transitions from ground to naïve, then from naïve to primed states of pluripotency were associated with increased durations of the G1 phase, and cyclin E-mediated alteration of the G1/S transition altered the balance between self-renewal and differentiation. LIF withdrawal resulted in a lengthening of the G1 phase in naïve ESCs, which occurred prior to the appearance of early lineage-specific markers, and could be reversed upon LIF supplementation. We concluded that the short G1 phase observed in murine ESCs was a determinant of naïve pluripotency and was partially under the control of LIF signaling.