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1.
J Clin Aesthet Dermatol ; 17(3): 42-47, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38495546

RESUMEN

Objective: We sought to explore facets of social media usage and the effect of the COVID-19 pandemic on the acceptance of cosmetic procedures. Methods: At an outpatient dermatology clinic from October 2019 to June 2022, 175 subjects who were English and Spanish speaking and aged 18 years or older were recruited. Participants completed a questionnaire including demographic information, social media usage, perceptions of cosmetic procedures, and desire to have a cosmetic procedure. Results were grouped into a pre-COVID-19 pandemic group and post-COVID-19 pandemic group due to a natural experiment that arose. Data were analyzed to ascertain the effect of social media usage and other factors that impact desire to undergo a cosmetic procedure between patients before and after the COVID-19 pandemic. Results: Factors resulting in differences in desire to have a cosmetic procedure included using photo editing applications (p=0.002), following celebrities and influencers on social media (p<0.001), and following social media accounts showing cosmetic results (p=0.013). There was a statistically significant change in number of participants that: followed social media accounts showing results of cosmetic procedures (pre-COVID: 31.9%, post-COVID: 50.6%, p=0.036); had thought about having a cosmetic procedure done (pre-COVID: 63.8%, post-COVID: 86.4%, p<0.001); had discussed cosmetic procedures with a physician, dermatologist, or other professional (pre-COVID: 43.6%, post-COVID: 67.9%, p=0.001); and believed that a cosmetic procedure would help their self-esteem (pre-COVID: 47.9%, post-COVID: 77.8%, p<0.001). Limitations: Limitations of this study include response bias, recall bias, and single institution study design, limiting generalizability. Conclusion: Our findings suggest that time spent on social media and use of photo-editing applications significantly contributes to desire to undergo a cosmetic procedure and contributed to the rise of cosmetic consultations during the COVID-19 pandemic.

3.
Global Surg Educ ; 2(1): 37, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38013876

RESUMEN

Purpose: Our goals were to characterize associations of author number, author gender, and institutional affiliation on ratings and acceptances of abstracts submitted to one surgical education conference over 5 years. Methods: We retrospectively reviewed all abstracts submitted between 2017 and 2021 to the annual meeting of the Association for Surgical Education (ASE). Abstract data included average rater scores, acceptance status, author lists, and institutional affiliations. We cross-referenced last author affiliation with top-40 National Institutes of Health (NIH)-funded institutions and used a gender determination software to code first and last author genders. Results: We analyzed 1,162 abstracts. Higher reviewer scores demonstrated positive, weak associations with more authors [r(1160) = 0.191, p < 0.001] and institutions [r(1160) = 0.182, p < 0.001]. Significantly higher scores were noted for abstracts with last authors affiliated with top-40 NIH-funded institutions [4.18 (SD 0.96) vs. 3.72 (SD 1.12), p < 0.001]. Women were first authors (51.8%) (n = 602) and last authors (35.4%) (n = 411) of the time. Abstracts were rated significantly higher with women rather than men as first authors [3.98 (SD 0.99) vs. 3.82 (SD 1.12), p = 0.011] or last [4.01 (SD 1.04) vs. 3.82 (SD 1.10), p = 0.005]. Across all years, abstracts were accepted more often as podium or plenary presentations when submitted by women first [n = 279, 59.7% (p = 0.002)] or last [n = 183, 38.4% (p = 0.095)] authors. Conclusion: Abstracts whose last authors were affiliated with top-40 NIH-funded institutions received significantly higher scores, possibly indicating increased tangible or intangible resources contributing to research efforts. Abstracts with women first and last authors scored higher and were more frequently invited for plenary and podium presentations.

5.
Immun Inflamm Dis ; 11(4): e804, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-37102660

RESUMEN

BACKGROUND: After introducing Covid-19 vaccines, a few side effects were reported, pityriasis rosea being one of them. Therefore, this study will systematically review its manifestation afteradministration. METHODS: Databases were searched, covering a timeline from December 1, 2019 to February 28, 2022. Data were independently extracted and accessed for bias. SPSS statistical software version 25 was used for appropriate inferential statistics. RESULTS: Thirty-one studies were included for data extraction after screening following the eligibility criteria. A total of 111 people were identified to have developed pityriasis rosea or pityriasis rosea-like eruptions after vaccination, out of which 36 (55.38%) were female. The average age of incidence was calculated to be 44.92 years, and 63 (62.37%) people presented after administration of the first dose. It was found popularly in the trunk area, either asymptomatically or with mild symptoms. Meantime the onset, was 8.58 days, and meantime it took to recover, was 6.44 weeks. CONCLUSION: The association between pityriasis rosea and pityriasis rosea-like eruptions after Covid-19 vaccines was established, but given the scarcity of studies, there is a need to conduct different clinical trials to confirm this association further and study the etiology and mechanism of the disease.


Asunto(s)
COVID-19 , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Pitiriasis Rosada , Humanos , Femenino , Adulto , Persona de Mediana Edad , Masculino , Pitiriasis Rosada/epidemiología , Pitiriasis Rosada/etiología , Pitiriasis Rosada/diagnóstico , Vacunas contra la COVID-19/efectos adversos , COVID-19/epidemiología , Vacunación
6.
Neuropsychiatr Dis Treat ; 19: 721-732, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37041856

RESUMEN

About 40% of the people with the obsessive-compulsive-disorder do not experience the desired outcome after the existing treatment, and its several side effects were reported. This systematic review was conducted to evaluate the efficacy and tolerability of alternative drugs and assess the possibility of their use as treatment options for obsessive-compulsive-disorder. The Scientific databases PubMed, Science Direct, Google Scholar, Cochrane, Directory of Open Access Journals, MedRxiv and BioRxiv, were searched from inception to March 2022, using appropriate search strategies for each drug and following the Prisma guidelines 2020. Studies were selected according to the already set criteria and assessed for bias. Data were extracted, and descriptive and continuous data were analyzed and presented as frequency/percentage and mean. A total of 16 observational and interventional studies were included for data extraction. The studies focused on four drugs, Psilocybin (n=4), Cannabis (n=7), Nicotine (n=3), and Morphine (n=2), that were used to test out their effect on OCD symptoms. Overall, the majority of the studies showed promising results by documenting a reduction in Y-BOCS scores. However, few subjects, specifically those using nicotine or Cannabis, did not affect their condition or self-reported worsening symptoms. Few side effects were also noticed. This systematic review found that the drugs mostly showed a positive response. All Psilocybin and morphine users, 88.2% and 74.1% of the nicotine and Cannabis users, respectively, reported experiencing the positive effect of these drugs, indicating that these drugs have the potential to be used in the management of OCD. However, further research is required in this arena to thoroughly understand the mechanism of action by which these drugs produce their therapeutic effect. Policies to destigmatize and encourage clinical trials with these drugs are crucial for exploring the use of these drugs as a treatment option for OCD.

7.
medRxiv ; 2023 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-36865147

RESUMEN

Rationale & Objective: The nasal passages harbor both commensal and pathogenic bacteria. In this study, we sought to characterize the anterior nasal microbiota in PD patients using 16S rRNA gene sequencing. Study Design: Cross-sectional. Setting & Participants: We recruited 32 PD patients, 37 kidney transplant (KTx) recipients, 22 living donor/healthy control (HC) participants and collected anterior nasal swabs at a single point in time. Predictors: We performed 16S rRNA gene sequencing of the V4-V5 hypervariable region to determine the nasal microbiota. Outcomes: Nasal microbiota profiles were determined at the genus level as well as the amplicon sequencing variant level. Analytical Approach: We compared nasal abundance of common genera among the 3 groups using Wilcoxon rank sum testing with Benjamini-Hochberg adjustment. DESeq2 was also utilized to compare the groups at the ASV levels. Results: In the entire cohort, the most abundant genera in the nasal microbiota included: Staphylococcus, Corynebacterium, Streptococcus , and Anaerococcus . Correlational analyses revealed a significant inverse relationship between the nasal abundance of Staphylococcus and that of Corynebacterium . PD patients have a higher nasal abundance of Streptococcus than KTx recipients and HC participants. PD patients have a more diverse representation of Staphylococcus and Streptococcus than KTx recipients and HC participants. PD patients who concurrently have or who developed future Staphylococcus peritonitis had a numerically higher nasal abundance of Staphylococcus than PD patients who did not develop Staphylococcus peritonitis. Limitations: 16S RNA gene sequencing provides taxonomic information to the genus level. Conclusions: We find a distinct nasal microbiota signature in PD patients compared to KTx recipients and HC participants. Given the potential relationship between the nasal pathogenic bacteria and infectious complications, further studies are needed to define the nasal microbiota associated with these infectious complications and to conduct studies on the manipulation of the nasal microbiota to prevent such complications.

8.
J Burn Care Res ; 44(4): 775-779, 2023 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-36645329

RESUMEN

Women are less likely to be senior authors, invited to write in scientific journals, and to be cited in high impact journals. The aim of this study was to investigate trends in authorship and gender differences in peer-reviewed burn literature over 13 years. We performed a retrospective analysis of original research articles published from January 2009 to September 2021 in three burn journals. A gender determination application was used to categorize the gender of the first and senior author. Of the 3908 articles analyzed, 42.5% had a woman first author and 27.6% had a woman senior author. We identified 2029 unique senior authors, 29.0% of whom were women. Woman senior authorship was associated with increased odds of woman first authorship [OR = 2.31 (95% CI: 2.00, 2.67); P < .001]. The percentage of papers with a woman senior author increased from 17.8% in 2009 to 35.7% in 2021. If this 1.0% (95% CI: 0.50-1.51%) linear trend increase per year in woman senior authorship continues, we will expect to see equal proportions of woman and man senior authors in the included journals starting in 2037. The field of burn care is far from reaching gender parity with respect to authorship of peer-reviewed publications. Supporting and encouraging gender-concordant and discordant first:last authorship dyads in mentorship as well as redistributing obligations that may detract from authorship opportunities are potential ways to improve parity in authorship and academia.


Asunto(s)
Quemaduras , Masculino , Humanos , Femenino , Estudios Retrospectivos , Quemaduras/terapia , Factores Sexuales , Autoria , Bibliometría
9.
Cureus ; 14(8): e27680, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36072166

RESUMEN

PURPOSE: Two-stage tissue expander (TE) to implant breast reconstruction is commonly performed by plastic surgeons. Prepectoral implant placement with acellular dermal matrix (ADM, e.g., AlloDerm®) reinforcement is evidenced by minimal postoperative pain. However, the same is not known for TE-based reconstruction. We performed this study to explore the use of complete AlloDerm® reinforcement of breast pocket tissues in women undergoing unilateral or bilateral mastectomies followed by immediate, two-stage tissue expansion in the prepectoral plane. METHODS: Patients (n = 20) aged 18-75 years were followed prospectively from their preoperative consult to 60 days post-TE insertion. The pain visual analog scale (VAS), Patient Pain Assessment Questionnaire, Subjective Pain Survey, Brief Pain Inventory-Short Form (BPI-SF), postoperative nausea and vomiting (PONV) survey, BREAST-Q Reconstruction Module, and short-form 36 (SF-36) questionnaires were administered. Demographic, intraoperative, and 30- and 60-day complications data were abstracted from medical records. After TE-to-implant exchange, patients were followed until 60 days postoperatively to assess for complications. RESULTS: Pain VAS and BPI-SF pain interference scores returned to preoperative values by 30 days post-TE insertion. Static and moving pain scores from the Patient Pain Assessment Questionnaire returned to preoperative baseline values by day 60. The mean subjective pain score was 3.0 (0.5 standard deviation) with seven patients scoring outside the standard deviation; none of these seven patients had a history of anxiety or depression. Median PONV scores remained at 0 from postoperative day 0 to day 7. Patient-reported opioid use dropped from 89.5% to 10.5% by postoperative day 30. BREAST-Q: Sexual well-being scores significantly increased from preoperative baseline to day 60 post-TE insertion. Changes in SF-36 physical functioning, physician limitations, emotional well-being, social functioning, and pain scores were significantly different from preoperative baseline to day 60 post-TE insertion. Five participants had complications within 60 days post-TE insertion. One participant experienced a complication within 60 days after TE-to-implant exchange. CONCLUSIONS: We describe pain scores, opioid usage, patient-reported outcomes data, and complication profiles of 20 consecutive patients undergoing mastectomy followed by immediate, two-stage tissue expansion in the prepectoral plane. We hope this study serves as a baseline for future research.

10.
Plast Reconstr Surg Glob Open ; 10(6): e4388, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35919889

RESUMEN

Background: This study investigates the effect of prophylactic perioperative antibiotic use on patients with small burns [≤20% total body surface area (TBSA)] on rates of infection, graft loss, or readmission. Methods: A retrospective chart review was conducted on patients admitted to our institution's burn center between January 2020 and July 2021. Patients were included if they had a 20% or less TBSA burn with 1 or more operating room visit for burn excision and were excluded if a preoperative infection was present. Data were gathered regarding patient demographics, burn mechanism, burn characteristics, and outcome measures including infection, graft loss, and readmission. Statistical analysis was conducted by Mann-Whitney U and Fisher exact tests, and P values reported at two-sided significance of less than 0.05. Results: There were no significant differences in age, body mass index, TBSA, percent third-degree burn, or comorbidities between patients who received (n = 29) or did not receive (n = 47) prophylactic perioperative antibiotics. There was a nonsignificant trend toward higher length of stay in the prophylactic antibiotic group, possibly driven by a nonsignificant trend toward higher rates of flame injuries in this group. There was no difference in infection (P = 0.544), graft loss (P = 0.494), or 30-day readmission (P = 0.584) between the two groups. Conclusion: This study finds no significant difference in postoperative infection, graft loss, or 30-day readmission in two similar patient cohorts who received or did not receive prophylactic perioperative antibiotics for acute excision of small (≤20% TBSA) burns.

11.
World J Gastroenterol ; 28(2): 216-229, 2022 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-35110946

RESUMEN

Alpha-fetoprotein (AFP) is an oncofetal glycoprotein that has been used as a tumor marker for hepatocellular carcinoma (HCC) in combination with ultrasound and other imaging modalities. Its utility is limited because of both low sensitivity and specificity, and discrepancies among the different methods of measurements. Moreover, its accuracy varies according to patient characteristics and the AFP cut-off values used. Combination of AFP with novel biomarkers such as AFP-L3, Golgi specific membrane protein (GP73) and des-gamma-carboxyprothrombin significantly improved its accuracy in detecting HCC. Increased AFP level could also signify severity of hepatic destruction and subsequent regeneration and is commonly observed in patients with acute and chronic liver conditions and cirrhosis. Hereditary and other non-hepatic disorders can also cause AFP elevation.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/diagnóstico por imagen , Humanos , Cirrosis Hepática , Neoplasias Hepáticas/diagnóstico por imagen , alfa-Fetoproteínas
12.
J Pak Med Assoc ; 72(11): 2355-2360, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37013327

RESUMEN

OBJECTIVE: To discover Pakistani adult population's perception about their general health, immune status and knowledge regarding immunity, and to highlight their efforts to improve it. METHODS: The knowledge-attitude-practice study was conducted from January to May 2021, after approval ethics review committee of the Islamic International Medical College, Rawalpindi, Pakistan, and comprised individuals of either gender from the community aged 18 years or more and not suffering from any physical disability or mental illness. Data was collected using a pre-tested, self-administered questionnaire that was disseminated through online platforms. The collected data was analysed using SPSS 25. RESULTS: All the 455(100%) individuals approached responded to the questionnaire. The mean age of the subjects was 22.6±7.579 years. There were 256(56.3%) female respondents, 283(62.2%) were aged 20-21 years, and 359(78.9%) hailed from the Sindh province. Most participants perceived their general health as 'good' 197(43.3%). The immune system function was reported 'good' by 200(44%), and the perception of general knowledge of immunity was reported 'good' by 189(41.5%) subjects. Inverse relationships were identified between stress levels and self-perceived health, and between receiving effective homeopathic treatment and 'very good' self-perceived immune status (p<0.05). People willing to take non-obligatory vaccines had a positive opinion about their self-perceived knowledge on immunity that produced a direct relationship (p<0.05). CONCLUSIONS: The findings provide a framework of practices that should be promoted to improve health status of adult population in Pakistan.


Asunto(s)
Pueblo Asiatico , Conocimientos, Actitudes y Práctica en Salud , Adulto , Humanos , Femenino , Adolescente , Adulto Joven , Masculino , Pakistán/epidemiología , Estudios Transversales , Encuestas y Cuestionarios
13.
Microorganisms ; 9(12)2021 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-34946209

RESUMEN

Hepatitis B virus (HBV) infection is a global public health issue and is a major cause of cirrhosis and hepatocellular carcinoma (HCC). Hepatitis D virus (HDV) requires the hepatitis B surface antigen (HBsAg) to replicate. The eradication of HBV, therefore, can also cure HDV. The current therapies for chronic hepatitis B and D are suboptimal and cannot definitely cure the viruses. In order to achieve functional or complete cure of these infections, novel therapeutic agents that target the various sites of the viral replicative cycle are necessary. Furthermore, novel immunomodulatory agents are also essential to achieve viral clearance. Many of these new promising compounds such as entry inhibitors, covalently closed circular DNA (cccDNA) inhibitors, small interfering RNAs (siRNAs), capsid assembly modulators and nucleic acid polymers are in various stages of clinical developments. In this review article, we provided a comprehensive overview of the structure and lifecycle of HBV, the limitations of the current therapies and a summary of the novel therapeutic agents for both HDV and HBV infection.

15.
J Clin Aesthet Dermatol ; 14(1): 38-44, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33584967

RESUMEN

BACKGROUND: Aging is an unavoidable biological process with many influencing factors, accounting for a multitude of visible manifestations on the hair as well as the skin. As the population ages while becoming more diverse, it is increasingly important to better understand the hair aging process. METHODS: A literature search was performed to review what is known about changes in hair structure over time, focusing on the differences in hair aging according to ethnic background. RESULTS: Sixty-nine publications were selected and information regarding hair structure, aging characteristics, and responses to extrinsic damage together with differences between races and ethnicities was collected. Hair-graying onset varies with race, with the average age for Caucasians being mid-thirties, that for Asians being late thirties, and that for Africans being mid-forties. Caucasians and Asians typically experience damage to the distal hair shaft, while African-Americans see damage occurring closer to the hair root. Postmenopausal changes include decreased anagen hairs in the frontal scalp, lower growth rates, and smaller hair diameters. CONCLUSION: There is a paucity of literature examining the characteristics of hair aging across all races. The unique characteristics of hair aging in different ethnicities provides information that will aid in a culturally sensitive approach and recommendations.

17.
Breast Cancer Res ; 22(1): 105, 2020 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-33023655

RESUMEN

BACKGROUND: ErbB2/HER2 oncoprotein often drives breast cancers (BCs) which are treated with the anti-ErbB2 antibody trastuzumab. The efficacy of trastuzumab-based metastatic BC therapies is routinely assessed by imaging studies. Trastuzumab typically becomes ineffective in the case of this disease and is then replaced by other drugs. Biomarkers of BC trastuzumab response could allow imaging studies and the switch to other drugs to occur earlier than is now possible. Moreover, bone-only BC metastases can be hard to measure, and biomarkers of their trastuzumab response could facilitate further treatment decisions. Such biomarkers are presently unavailable. In this study, we searched for proteins whose levels in BC cell-emitted extracellular vesicles (EVs) potentially correlate with BC trastuzumab sensitivity. METHODS: We isolated EVs from cultured trastuzumab-sensitive and trastuzumab-resistant human BC cells before and after trastuzumab treatment and characterized these EVs by nanoparticle tracking analysis and electron microscopy. We found previously that ErbB2 drives BC by downregulating a pro-apoptotic protein PERP. We now tested whether trastuzumab-induced PERP upregulation in EVs emitted by cultured human BC cells correlates with their trastuzumab sensitivity. We also used mass spectrometry to search for additional proteins whose levels in such EVs reflect BC cell trastuzumab sensitivity. Once we identified proteins whose EV levels correlate with this sensitivity in culture, we explored the feasibility of testing whether their levels in the blood EVs of trastuzumab-treated metastatic BC patients correlate with patients' response to trastuzumab-based treatments. RESULTS: We found that neither trastuzumab nor acquisition of trastuzumab resistance by BC cells affects the size or morphology of EVs emitted by cultured BC cells. We established that EV levels of proteins PERP, GNAS2, GNA13, ITB1, and RAB10 correlate with BC cell trastuzumab response. Moreover, these proteins were upregulated during trastuzumab-based therapies in the blood EVs of a pilot cohort of metastatic BC patients that benefited from these therapies but not in those derived from patients that failed such treatments. CONCLUSIONS: Upregulation of a protein set in EVs derived from cultured breast tumor cells correlates with tumor cell trastuzumab sensitivity. It is feasible to further evaluate these proteins as biomarkers of metastatic BC trastuzumab response.


Asunto(s)
Biomarcadores Farmacológicos/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Vesículas Extracelulares/metabolismo , Proteínas de la Membrana/metabolismo , Receptor ErbB-2/metabolismo , Trastuzumab/uso terapéutico , Adulto , Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Cromograninas/metabolismo , Estudios de Cohortes , Femenino , Subunidades alfa de la Proteína de Unión al GTP G12-G13/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gs/metabolismo , Genes Supresores de Tumor , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Proteómica/métodos , Receptor ErbB-2/antagonistas & inhibidores , Regulación hacia Arriba , Proteínas de Unión al GTP rab/metabolismo
18.
Artículo en Inglés | MEDLINE | ID: mdl-31528290

RESUMEN

Deferasirox is a recently approved iron chelator and is widely used to treat iron overload in transfusion-dependent patients. Its once-daily dosing and oral route of administration have made it an appealing alternative to deferoxamine. Recent case studies have brought to light its potential to cause damage to the proximal convoluted tubule resulting in Fanconi syndrome (FS). FS is a proximal tubular dysfunction that leads to glycosuria, phosphaturia, aminoaciduria, and normal anion gap metabolic acidosis. Herein, we discuss a case of a young male on chronic blood transfusions requiring deferasirox therapy, who was found to have FS from its use. We discuss the possible mechanism of drug toxicity and the need for regular monitoring of serum electrolytes andurinalysis along with renal function tests to avoid this consequence.

19.
DNA Repair (Amst) ; 82: 102697, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31499327

RESUMEN

Homologous recombination deficiency conferred by alterations in BRCA1 or BRCA2 are common in breast tumors and can drive sensitivity to platinum chemotherapy and PARP inhibitors. Alterations in nucleotide excision repair (NER) activity can also impact sensitivity to DNA damaging agents, but NER activity in breast cancer has been poorly characterized. Here, we apply a novel immunofluorescence-based cellular NER assay to screen a large panel of breast epithelial and cancer cell lines. Although the majority of breast cancer models are NER proficient, we identify an example of a breast cancer cell line with profound NER deficiency. We show that NER deficiency in this model is driven by epigenetic silencing of the ERCC4 gene, leading to lack of expression of the NER nuclease XPF, and that ERCC4 methylation is also strongly correlated with ERCC4 mRNA and XPF protein expression in primary breast tumors. Re-expression of XPF in the ERCC4-deficient breast cancer rescues NER deficiency and cisplatin sensitivity, but does not impact PARP inhibitor sensitivity. These findings demonstrate the potential to use functional assays to identify novel mechanisms of DNA repair deficiency and nominate NER deficiency as a platinum sensitivity biomarker in breast cancer.


Asunto(s)
Neoplasias de la Mama/patología , Reparación del ADN , Línea Celular Tumoral , Cisplatino/farmacología , Roturas del ADN de Doble Cadena/efectos de los fármacos , Roturas del ADN de Doble Cadena/efectos de la radiación , Metilación de ADN/efectos de los fármacos , Metilación de ADN/efectos de la radiación , Reparación del ADN/efectos de los fármacos , Reparación del ADN/genética , Reparación del ADN/efectos de la radiación , Proteínas de Unión al ADN/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de la radiación , Humanos , Regiones Promotoras Genéticas/genética , Rayos Ultravioleta
20.
Breast Cancer Res ; 20(1): 151, 2018 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-30545388

RESUMEN

BACKGROUND: The ability of solid tumor cells to resist anoikis, apoptosis triggered by cell detachment from the extracellular matrix (ECM), is thought to be critical for 3D tumor growth. ErbB2/Her2 oncoprotein is often overproduced by breast tumor cells and blocks their anoikis by partially understood mechanisms. In our effort to understand them better, we observed that detachment of nonmalignant human breast epithelial cells from the ECM upregulates the transcription factor Irf6. Irf6 is thought to play an important role in mammary gland homeostasis and causes apoptosis by unknown mechanisms. We noticed that ErbB2, when overproduced by detached breast epithelial cells, downregulates Irf6. METHODS: To test whether ErbB2 downregulates Irf6 in human ErbB2-positive breast cancer cells, we examined the effect of ErbB2 inhibitors, such as the anti-ErbB2 antibody trastuzumab or the ErbB2/epidermal growth factor receptor small-molecule inhibitor lapatinib, on Irf6 in these cells. Moreover, we performed Irf6 IHC analysis of tumor samples derived from the locally advanced ErbB2-positive breast cancers before and after neoadjuvant trastuzumab-based therapies. To examine the role of Irf6 in anoikis of nonmalignant and ErbB2-overproducing breast epithelial cells, we studied anoikis after knocking down Irf6 in the former cells by RNA interference and after overproducing Irf6 in the latter cells. To examine the mechanisms by which cell detachment and ErbB2 control Irf6 expression in breast epithelial cells, we tested the effects of genetic and pharmacological inhibitors of the known ErbB2-dependent signaling pathways on Irf6 in these cells. RESULTS: We observed that trastuzumab and lapatinib upregulate Irf6 in ErbB2-positive human breast tumor cells and that neoadjuvant trastuzumab-based therapies tend to upregulate Irf6 in human breast tumors. We found that detachment-induced Irf6 upregulation in nonmalignant breast epithelial cells requires the presence of the transcription factor ∆Np63α and that Irf6 mediates their anoikis. We showed that ErbB2 blocks Irf6 upregulation in ErbB2-overproducing cells by activating the mitogen-activated protein kinases that inhibit ∆Np63α-dependent signals required for Irf6 upregulation. Finally, we demonstrated that ErbB2-driven Irf6 downregulation in ErbB2-overproducing breast epithelial cells blocks their anoikis and promotes their anchorage-independent growth. CONCLUSIONS: We have demonstrated that ErbB2 blocks anoikis of breast epithelial cells by downregulating Irf6.


Asunto(s)
Antineoplásicos/farmacología , Neoplasias de la Mama/patología , Transformación Celular Neoplásica/patología , Factores Reguladores del Interferón/metabolismo , Receptor ErbB-2/metabolismo , Anoicis/efectos de los fármacos , Antineoplásicos/uso terapéutico , Biopsia , Mama/citología , Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Técnicas de Cultivo de Célula , Línea Celular , Estudios de Cohortes , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Matriz Extracelular/metabolismo , Matriz Extracelular/patología , Femenino , Humanos , Factores Reguladores del Interferón/genética , Terapia Neoadyuvante/métodos , Proyectos Piloto , ARN Interferente Pequeño/metabolismo , Receptor ErbB-2/antagonistas & inhibidores , Trastuzumab/farmacología , Trastuzumab/uso terapéutico , Regulación hacia Arriba/efectos de los fármacos
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