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1.
J Racial Ethn Health Disparities ; 11(2): 826-833, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36959392

RESUMO

PURPOSE: Obesity and weight gain in breast cancer survivors leads to a greater risk of recurrence and a decreased chance of survival. A paucity of data exists regarding strengths, weaknesses, and barriers for implementing culturally sensitive, patient-centered interventions for weight management among minority communities. The objective of this study was to evaluate breast cancer patients' experience and perspectives regarding weight management in a racially diverse population. METHODS: Semi-structured qualitative interviews were conducted with breast cancer patients with a body mass index ≥ 25 kg/m2 regarding their experience with weight management. Interviews were transcribed verbatim, and a thematic analysis was conducted. RESULTS: Participants (n = 17) most commonly self-identified as non-Hispanic Black (70.6%). Nearly all participants felt comfortable being approached about weight management, yet less than half (41.2%) reported that they knew about the link between breast cancer and body weight prior to the interview. Four themes emerged: (1) lack of knowledge regarding the link between body weight and breast cancer risk, (2) barriers to weight management including family stressors, high cost, mental health issues, and chronic medical conditions, (3) previous attempts at weight loss including bariatric surgery, and (4) best practices for approaching weight management including discussion of weight management prior to survivorship. CONCLUSION: There is a need for a multidisciplinary, patient-centered weight management program for minority breast cancer patients that improves awareness of the link between weight and breast cancer risk. Weight management should be introduced early on as an element of the treatment plan for breast cancer.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Obesidade/psicologia , Redução de Peso , Índice de Massa Corporal , Grupos Minoritários , Pesquisa Qualitativa
2.
Ann Surg Oncol ; 31(3): 1455-1467, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38055093

RESUMO

BACKGROUND: Asian American (AsAm) women have some of the lowest rates of up-to-date breast cancer screening, and lack of disaggregated racial/ethnic data can mask disparities. We evaluated presentation patterns among AsAms at two hospitals with distinct communities: New York Presbyterian-Queens (NYPQ), in Flushing, Queens and Weill Cornell Medical Center (WCM), on the Upper East Side (UES) neighborhood of Manhattan. PATIENTS AND METHODS: Patients with newly diagnosed breast cancer between January 2019 and December 2022 were identified using a prospective database and clinical data collected. Patients were categorized as self-reported Asian versus Non-Asian. The Asian group was disaggregated as Chinese-Asian versus Other-Asian. Physician workforce data were obtained from public records. RESULTS: A total of 3546 patients (1162 NYPQ, 2384 WCM) were included. More NYPQ patients identified as Asian compared with WCM (49 vs. 14%, p < 0.001). Asian patients were mostly East Asian Chinese (NYPQ 61%, WCM 53%). More Chinese patients at NYPQ reported Chinese as their preferred language (81 vs. 33%, p < 0.001). Greatest differences of screen-detected disease frequency were seen between NYPQ and WCM Chinese patients (75 vs. 59%, p < 0.001). Eighty percent of NYPQ Chinese patients presented with stage 0/I disease versus 69% at WCM (p = 0.007), a difference not observed between Other-Asian patients (75% NYPQ, 68% WCM, p = 0.095). 3% of UES physicians versus 16% in Flushing reported speaking Chinese. CONCLUSIONS: Chinese patients residing in a neighborhood with more Chinese-speaking physicians more frequently presented with screen-detected, early-stage breast cancer. Stage distribution differences were not apparent among the aggregated pool of Other-Asian patients, suggesting cancer disparities may be masked when ethnic groups are studied in aggregate.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Asiático , Cidade de Nova Iorque , Incidência , Detecção Precoce de Câncer
5.
Psychooncology ; 32(7): 1106-1113, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37212636

RESUMO

OBJECTIVE: Treatment delays in combination with general social distancing practices to reduce transmission may have negative impacts on the mental health of women with breast cancer who may need more social and emotional support. We sought to elucidate the psychosocial effects of the COVID-19 pandemic among women with and without breast cancer in New York City. METHODS: We conducted a prospective cohort study among women aged 18+ across the spectrum of breast health care at New York Presbyterian (NYP)-Weill Cornell, NYP-Brooklyn Methodist Hospital and NYP-Queens. Women were contacted between June and October 2021 to assess their self-reported depression, stress, and anxiety during the COVID-19 pandemic. We compared women who were recently diagnosed, those with a history of breast cancer, and women without cancer whose other health visits were delayed during the pandemic. RESULTS: There were 85 women who completed the survey. Breast cancer survivors (42%) were the least likely to report a delay in care due to COVID compared to breast cancer patients who were recently diagnosed (67%) and women without cancer (67%). Compared to women without cancer and breast cancer survivors, women recently diagnosed with breast cancer reported higher levels of anxiety and depression with a statistically significant difference in perceived stress. CONCLUSIONS: Our findings highlight the need to identify and risk-stratify patients facing a new breast cancer diagnosis in and around the COVID-19 pandemic who may benefit from additional resources to mitigate the adverse impacts of the pandemic and a breast cancer diagnosis on psychosocial health.


Assuntos
Neoplasias da Mama , COVID-19 , Humanos , Feminino , COVID-19/epidemiologia , COVID-19/psicologia , Pandemias , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/terapia , Neoplasias da Mama/psicologia , Estudos Prospectivos , Ansiedade/epidemiologia , Depressão/epidemiologia
6.
Ann Surg Oncol ; 30(8): 4648-4656, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36681737

RESUMO

BACKGROUND: Despite increased utilization of contralateral prophylactic mastectomy (CPM), there is insufficient evidence that it improves survival in average-risk women with unilateral breast cancer. CPM may be of heightened interest to patients with triple negative breast cancer (TNBC) because these patients are more likely to have BRCA1 mutation-associated disease and are not candidates for the chemoprevention benefits of adjuvant endocrine therapy. METHODS: Survival and recurrence outcomes were evaluated for all TNBC patients from a multi-institutional database (1999-2018) at two academic cancer programs in two metropolitan cities of the Northeast and Midwest. Median follow-up time was 3.7 years. RESULTS: Seven hundred and nighty six TNBC patients were evaluated and 15.45% underwent CPM. Women undergoing CPM were more likely to be white (p < 0.001), younger (p < 0.001), and underwent genetic testing (p < 0.001). A borderline survival benefit was observed for TNBC patients undergoing CPM (5-year overall survival 95.1% vs. 85.0%; p = 0.05). There was no difference in survival when BRCA mutation carriers were excluded (5-year overall survival 94.1% vs. 85.2%; p = 0.12). For BRCA mutation carriers, a numeric trend was observed for improved survival for patients undergoing CPM (5-year overall survival 97.2% vs. 84.1%; p = 0.35). Among patients not undergoing CPM, the rate of developing a new primary breast cancer was 2.2% (15/673). Among these 15 patients, 20% (3/15) were known BRCA mutation carriers. CONCLUSIONS: Our data demonstrate no survival benefit for TNBC patients without BRCA1/2 mutations undergoing CPM.


Assuntos
Neoplasias da Mama , Mastectomia Profilática , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Mastectomia , Proteína BRCA1/genética , Neoplasias de Mama Triplo Negativas/cirurgia , Neoplasias da Mama/genética , Neoplasias da Mama/cirurgia , Mutação , Proteína BRCA2/genética
7.
Curr Breast Cancer Rep ; 14(4): 213-221, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36530340

RESUMO

Purpose of Review: Despite significant advances in detection and treatment for breast cancer, the breast cancer mortality rate for Black women remains 40% higher than that for White women. Timely work-up and treatment improve outcomes, yet no gold standard exists for which to guide providers. Recent Findings: A large body of literature demonstrates disparities in time to treatment for breast cancer, and most studies show that Black women receive treatment later than their White counterparts. The COVID-19 pandemic has been projected to worsen these disparities, but the extent of this impact remains unknown. Summary: In this review, we describe the available evidence on disparities in time to treatment, potential drivers, and possible mitigation strategies. Future research must address how the COVID-19 pandemic has impacted the timely treatment of breast cancer patients, particularly populations vulnerable to disparate outcomes. Improved access to multidisciplinary breast programs, patient navigation services, and establishment of standards for timely treatment are necessary.

8.
Curr Breast Cancer Rep ; 14(4): 205-212, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36467667

RESUMO

Purpose of Review: Socioeconomically disadvantaged populations and minority groups suffer from high breast cancer mortality, a disparity caused by decreased access to specialty care, lower treatment adherence, co-morbidities, and genetic predisposition for biologically aggressive breast tumor subtypes. Telehealth has the potential to mitigate breast cancer disparities by increasing access to specialty care and health information. However, unequal access to high-speed/broadband internet service and telehealth itself magnifies breast cancer disparities in vulnerable populations. This review evaluates the impact of the digital divide on breast cancer outcomes, as well as strategies for leveraging telehealth to reduce breast cancer disparities. Recent Findings: There is a paucity of research specific to employing telehealth to address breast cancer disparities. Previous studies provide examples of telehealth utilization for increasing screening mammography, in addition to improving access to breast cancer care, including breast cancer specialist, nurse navigators, and clinical trials. Telehealth can also be used as an approach to risk reduction, with strategies to support weight management and genetic testing. Summary: Eliminating the digital divide holds enormous potential for mitigating breast cancer disparities through an intentional focus on improving access to telehealth. With increased accessibility, resource allocation, and improved digital infrastructure, telehealth can be used to address disparities in early detection, quality of breast cancer care, treatment adherence, and risk assessment. Further research is essential to elucidate best practices in breast cancer telehealth approaches in underserved communities.

9.
Curr Breast Cancer Rep ; 14(4): 192-198, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059579

RESUMO

Purpose of Review: The COVID-19 pandemic has placed unprecedented challenges on breast cancer patients and health care providers. The impact of the pandemic on preexisting breast cancer disparities remains unknown but is projected to have adverse outcomes. Recent Findings: Early work has demonstrated that pandemic-related temporary suspensions in breast cancer screening, interruption of clinical trials, and treatment delays have an adverse impact on breast cancer patient outcomes and may worsen disparities. Summary: In this review, we highlight existing knowledge regarding breast cancer disparities and the impact of the COVID-19 pandemic. Strategies for mitigating disparities moving forward include targeted research evaluating race-specific outcomes, targeted education for providers regarding breast health disparities, improved access to telehealth, maintenance of patient navigation programs, and patient education regarding the safety and necessity of enrollment in clinical trials.

10.
Curr Breast Cancer Rep ; 14(4): 199-204, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091940

RESUMO

Purpose of Review: Breast cancer is the most commonly diagnosed cancer in women, and the leading cause of cancer death. However, racial and ethnic minority groups, as well as rural and underserved populations, face disparities that limit their access to specialty care for breast cancer. To address these disparities, health care providers can leverage an electronic health record (EHR). Recent Findings: Few studies have evaluated the potential benefits of using EHRs to address breast cancer disparities, and none of them outlines a standard approach for this effort. However, these studies outline that EHRs can be used to identify and notify patients at risk for breast cancer. These systems can also automate referrals and scheduling for screening and genetic testing, as well as recruit eligible patients for clinical trials. EHRs can also provide educational materials to reduce risks associated with modifiable risk factors, such as physical activity, obesity, and smoking. These systems can also support telemedicine visits and centralize inter-institutional communication to improve treatment adherence and the quality of care. Summary: EHRs have tremendous potential to increase accessibility and communication for patients with breast cancer by augmenting patient engagement, improving communication between patients and providers, and strengthening communication among providers. These efforts can reduce breast cancer disparities by increasing breast cancer screening, improving treatment adherence, expanding access to specialty care, and promoting risk-reducing habits among racial and ethnic minority groups and other underserved populations.

11.
Am J Surg ; 224(4): 1039-1045, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35641320

RESUMO

BACKGROUND: The impact of the COVID-19 mammography screening hiatus as well as of post-hiatus efforts promoting restoration of elective healthcare on breast cancer detection patterns and stage distribution is unknown. METHODS: Newly diagnosed breast cancer patients (2019-2021) at the New York Presbyterian (NYP) Hospital Network were analyzed. Chi-square and student's t-test compared characteristics of patients presenting before and after the screening hiatus. RESULTS: A total of 2137 patients were analyzed. Frequency of screen-detected and early-stage breast cancer declined post-hiatus (59.7%), but returned to baseline (69.3%). Frequency of screen-detected breast cancer was lowest for African American (AA) (57.5%) and Medicaid patients pre-hiatus (57.2%), and this disparity was reduced post-hiatus (65.3% for AA and 63.2% for Medicaid). CONCLUSIONS: The return to baseline levels of screen-detected cancer, particularly among AA and Medicaid patients suggest that large-scale breast health education campaigns may be effective in resuming screening practices and in mitigating disparities.


Assuntos
Neoplasias da Mama , COVID-19 , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/prevenção & controle , COVID-19/epidemiologia , Detecção Precoce de Câncer , Feminino , Disparidades em Assistência à Saúde , Humanos , Mamografia , Programas de Rastreamento , Cidade de Nova Iorque/epidemiologia , Estados Unidos
12.
Ann Surg Oncol ; 29(9): 5437-5444, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35583690

RESUMO

BACKGROUND: Postmastectomy breast reconstruction is an essential element of multidisciplinary breast cancer care but may be underutilized. METHODS: This retrospective study analyzed mastectomy patients (2018-2021) at an urban hospital. Multivariable logistic regression was performed, and a mixed-effects logistic regression model was constructed to determine patient-level factors (age, race, body mass index, comorbidities, smoking status, insurance, type of surgery) and provider-level factors (breast surgeon gender, participation in multidisciplinary breast clinic) that influence reconstruction. RESULTS: Overall, 167 patients underwent mastectomy. The reconstruction rate was 35%. In multivariable analysis, increasing age (odds ratio [OR] 0.95; 95% confidence interval [CI] 0.91-0.99) and Medicaid insurance (OR 0.18; 95% CI 0.06-0.53) relative to private insurance were negative predictors, whereas bilateral mastectomy was a positive predictor (OR 7.07; 95% CI 2.95-17.9) of reconstruction. After adjustment for patent age, race, insurance, and type of surgery, female breast surgeons had 3.7 times greater odds of operating on patients who had reconstruction than males (95% CI 1.20-11.42). CONCLUSION: Both patient- and provider-level factors have an impact on postmastectomy reconstruction. Female breast surgeons had nearly four times the odds of caring for patients who underwent reconstruction, suggesting that a more standardized process for plastic surgery referral is needed.


Assuntos
Neoplasias da Mama , Mamoplastia , Cirurgiões , Neoplasias da Mama/cirurgia , Feminino , Disparidades em Assistência à Saúde , Hospitais Urbanos , Humanos , Masculino , Mastectomia , Estudos Retrospectivos , Estados Unidos
13.
Breast Cancer Res Treat ; 192(1): 163-173, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35022867

RESUMO

PURPOSE: National comprehensive cancer network guidelines recommend delivery of adjuvant chemotherapy in node-negative triple-negative breast cancer (TNBC) if the tumor is > 1 cm and consideration of adjuvant chemotherapy for T1b but not T1a disease. These recommendations are based upon sparse data on the role of adjuvant chemotherapy in T1a and T1b node-negative TNBC. Our objective was to clarify the benefits of chemotherapy for patients with T1N0 TNBC, stratified by tumor size. METHODS: We performed a retrospective analysis of survival outcomes of TNBC patients at two academic institutions in the United States from 1999 to 2018. Primary tumor size, histology, and nodal status were based upon surgical pathology. The Kaplan-Meier plot and 5-year unadjusted survival probability were evaluated. RESULTS: Among 282 T1N0 TNBC cases, the status of adjuvant chemotherapy was known for 258. Mean follow-up was 5.3 years. Adjuvant chemotherapy was delivered to 30.5% of T1a, 64.7% T1b, and 83.9% T1c (p < 0.0001). On multivariable analysis, factors associated with delivery of adjuvant chemotherapy were tumor size and grade 3 disease. Improved overall survival was associated with use of chemotherapy in patients with T1c disease (93.2% vs. 75.2% p = 0.008) but not T1a (100% vs. 100% p = 0.3778) or T1b (100% vs. 95.8% p = 0.2362) disease. CONCLUSION: Our data support current guidelines indicating benefit from adjuvant chemotherapy in node-negative TNBC associated with T1c tumors but excellent outcomes were observed in the cases of T1a and T1b disease, regardless of whether adjuvant chemotherapy was delivered.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Quimioterapia Adjuvante , Feminino , Humanos , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia
14.
Clin Imaging ; 80: 430-437, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34543867

RESUMO

PURPOSE: Screening mammography improves breast cancer survival through early detection, but Triple Negative Breast Cancer (TNBC) is more difficult to detect on mammography and has lower survival compared to non-TNBC, even when detected at early stages. TNBC is twice as common among African American (AA) compared to White American (WA) women, thereby contributing to the 40% higher breast cancer mortality rates observed in AA women. The role of screening mammography in addressing breast cancer disparities is therefore worthy of study. METHODS: Outcomes were evaluated for TNBC patients treated in the prospectively-maintained databases of academic cancer programs in two metropolitan cities of the Northeast and Midwest, 1998-2018. RESULTS: Of 756 TNBC cases, 301 (39.8%) were mammographically screen-detected. 46% of 189 AA and 38.5% of 460 WA patients had screen-detected TNBC (p = 0.16). 25.3% of 257 TNBC cases ≤50 years old had screen-detected disease compared to 47.3% of 499 TNBC cases >50 years old (p < 0.0001). 220/301 (73.1%) screen-detected TNBC cases were T1 lesions versus 118/359 (32.9%) non-screen-detected cases (p < 0.0001). Screen-detected TNBC was more likely to be node-negative (51.9% v. 40.4%; p < 0.0001). Five-year overall survival was better in screen-detected TNBC compared to nonscreen-detected TNBC (92.8% v. 81.5%; p < 0.0001) in the entire cohort. The magnitude of this effect was most significant among AA patients (Fig. 1). Screening-related survival patterns were similar among AA and WA patients in both cities. CONCLUSION: Data from two different cities demonstrates the value of screening mammography to mitigate breast cancer disparities in AA women through the early detection of TNBC.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Negro ou Afro-Americano , Neoplasias da Mama/diagnóstico por imagem , Detecção Precoce de Câncer , Feminino , Humanos , Mamografia , Pessoa de Meia-Idade , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , População Branca
15.
Ann Surg Oncol ; 28(11): 6032-6040, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33876349

RESUMO

BACKGROUND: The optimal management of intraductal papillomas (IPs) without atypia diagnosed on needle core biopsy (NCB) is unclear. This study analyzed the malignancy risk of immediately excised IPs and characterized the behavior of IPs under active surveillance (AS). METHODS: We retrospectively reviewed the pathology and imaging records of patients diagnosed with IPs without atypia on NCB during a 10-year period (1999-2019). The malignancy upgrade rate was assessed in patients who had an immediate surgical excision, and the rates of both radiographic progression and development of malignancy were assessed in a cohort of patients undergoing AS. RESULTS: The inclusion criteria were met in 152 patients with 175 IPs with a mean age of 51 ± 13 years. The average size of the IPs on initial imaging was 8 ± 4 mm. Most of the lesions (57%, n = 99) were immediately excised, whereas 76 (43%) underwent AS with interval imaging with a median follow-up period of 15 months (range, 5-111 months). Among the immediately excised IPs, surgical pathology revealed benign findings in 97% (n = 96) and ductal carcinoma in situ in 3% (n = 3). In the AS cohort, 72% (n = 55) of the IPs remained stable, and 25% (n = 19) resolved or decreased in size. At 2 years, 4% had increased in size on imaging and were subsequently excised, with ductal carcinoma in situ (DCIS, n = 1) and benign pathology (n = 1) noted on final pathology. CONCLUSIONS: In a large series of breast IPs without atypia, no invasive carcinoma was observed after immediate excision, and 96% of the lesions had not progressed on AS. This suggests that patients with IP shown on NCB can safely undergo AS, with surgery reserved for radiographic lesion progression.


Assuntos
Carcinoma Intraductal não Infiltrante , Papiloma Intraductal , Adulto , Biópsia com Agulha de Grande Calibre , Humanos , Pessoa de Meia-Idade , Papiloma Intraductal/epidemiologia , Papiloma Intraductal/cirurgia , Prevalência , Estudos Retrospectivos , Conduta Expectante
16.
Appl Immunohistochem Mol Morphol ; 28(5): 354-359, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30585786

RESUMO

Studies have suggested that perineural invasion (PNI) and lymphovascular invasion (LVI) serve as independent prognostic factors in colorectal cancer (CRC). Currently, little is known regarding the combination of PNI and LVI as prognostic factors, independent of stage. We hypothesized that this combination was a better prognostic marker than either PNI or LVI alone, and that S100 staining would detect PNI not seen with hematoxylin and eosin (H&E). Surgical pathology slides were retrospectively reviewed for 151 stages I to IV CRC patients who had surgery between January 1, 2008 and December 8, 2008 at 3 Hackensack Meridian Health hospitals in New Jersey. PNI and LVI were detected by H&E staining and a subset of 127 patient samples were additionally examined for PNI by S100 staining. Correlation between staining characteristics and patient outcomes was assessed using the Pearson χ tests and the Fisher exact tests. Survival was analyzed using Kaplan-Meier methods. Of the 151 cases reviewed, 30.5% were positive for PNI and 35.1% were positive for LVI by H&E. The use of S100 staining for PNI enabled its detection in 27 additional cases. Median time from patient diagnosis to death was significantly shorter for patients who were positive for both PNI and LVI (P<0.001). PNI and LVI were individual markers for poor survival in CRC patients and their combined presence had an even worse outcome. Failure to detect PNI on H&E can be overcome by S100 staining.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/metabolismo , Nervos Periféricos/metabolismo , Proteínas S100/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Nervos Periféricos/patologia , Prognóstico , Estudos Retrospectivos , Coloração e Rotulagem , Taxa de Sobrevida
17.
Basic Clin Androl ; 28: 14, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30473791

RESUMO

BACKGROUND: Bacterial infection and inflammation of the testis impairs fertility, yet an understanding of inflammatory responses of the testis is incomplete. We are interested in identifying gene pathways involved in the detection and clearance of infectious microbes in the male reproductive tract. In previous studies in our lab focused on hypoxia-responsive genes of the testis, preliminary experiments suggested that genes classically categorized as hypoxia genes are also activated during antimicrobial responses. The purpose of this study was to identify hypoxia and inflammatory gene pathways that contribute to antimicrobial protection of the testis and to consider possible cross-talk and interactions between these pathways. Inflammation was induced in Sprague-Dawley rats using P. aeruginosa or E. coli lipopolysaccharide (LPS). Levels of hypoxia-inducible factor-1 (HIF-1α) protein and nuclear factor kappa B (NF-κB) were measured, and hypoxia and inflammatory gene expression patterns in testis were analyzed by gene expression profiling using real-time quantitative PCR arrays. RESULTS: In LPS-treated rats, HIF-1α protein increased with no change in Hif-1α mRNA. Western Blot analysis also demonstrated no change in NF-κB and inhibitory NFKB alpha (IκBα) protein levels following LPS treatment. Five hypoxia pathway genes (Angptl4, Egr1, Ier3, Pai1, and Glut1), and 11 inflammatory pathway genes (Ccl12, Cc13, Cd14, Cxcl10, Icam1, Il10, Il1b, Il6, Nfkbia, Tlr2, Tnf) up-regulated after 3 h of inflammation. Angptl4, Ccl12, Cc13, Cd14, Egr1, Nfkbia, Tlr2, and Tnf remained elevated at 6 h. Six genes were up-regulated at 6 h only (Bhlhe40, C3, Jak2, Nlrp3, Slc11a1, Tlr1). One gene (Tlr5) was down-regulated after 3 h and no genes at 6 h. Electrophoretic mobility shift assay results suggest a decrease in NF-κB binding activity following LPS treatment. CONCLUSIONS: Testicular HIF-1α is up-regulated following LPS-induced inflammation. In contrast to other tissues, in which HIF-1α is up-regulated through transcriptional activation via NF-κB, we conclude that HIF-1α in the testis is not up-regulated through an increase in Hif-1α mRNA or through NF-κB-dependent mechanisms. Hypoxia pathway genes and genes involved in Toll-like receptor (TLR) and cytokine-mediated signaling comprise major functional categories of up-regulated genes, demonstrating that both hypoxia and classic inflammatory pathways are involved in inflammatory responses of the testis.


CONTEXTE: L'infection et l'inflammation bactériennes du testicule altèrent la fertilité; cependant la compréhension des réponses inflammatoires du testicule est. encore incomplète. Nous nous sommes intéressés à l'identification des voies des gènes impliqués dans la détection et l'élimination des microbes infectieux dans l'appareil reproductif masculin. Dans de précédentes études menées dans notre laboratoire, et centrées sur des gènes sensibles à l'hypoxie, les expérimentations préliminaires suggéraient que les gènes classiquement catégorisés comme gènes de l'hypoxie étaient aussi activés au cours des réponses antimicrobiennes. Le but de la présente étude était d'identifier les voies des gènes qui contribuaient à la protection antimicrobienne du testicule et d'examiner de potentiels intermodulations et interactions entre ces voies.L'inflammation a été induite chez des rats Sprague-Dawley en utilisant des lypopolysaccharides (LPS) de P. aeruginosaet d'E. coli. Les taux de protéine du facteur-1 inductible par l'hypoxie (HIF1- α) et du facteur nucléaire kappa B (NF- kB) ont été mesurés; les profils d'expression des gènes de l'hypoxie et de l'inflammation dans le testicule ont été analysés par profilage de l'expression génique par PCR quantitative en temps réel. RÉSULTATS: Chez les rats traités par LPS, la protéine HIF-1 α a augmenté sans modification de Hif-1αmRNA. L'analyse par Western Blot a aussi montré l'absence de modifications des taux de NF-kB et de la protéine inhibitrice NFKB alpha (IkB α) après traitement. Cinq gènes de la voie hypoxie (Angptl4, Egr1, Ier3, Pai1,et Glut1), et 11 gènes de la voie inflammatoire (Ccl12, Cc13, Cd14, Cxcl10, Icam1, Il10, Il1b, Il6, Egr1, Nfkbia, Tlr2, et Tnf) ont été régulés à la hausse après 3 heures d'inflammation. Angptl4, Ccl12, Cc13, Cd14, Egr1, Nfkbia, Tlr2, et Tnfsont restés élevés à 6 heures. Six gènes n'ont ont été régulés à la hausse qu'à 6 heures (Bhlhe40, C3, Jak2, Nlrp3, Slc11a1, Tlr1). Un gène (Tlr5) a été régulé à la baisse après 3 heures et aucun gène à 6 heures. Les résultats du test de décalage de la mobilité électrophorétique suggèrent une baisse de l'activité de liaison de NF- kB après traitement par LPS. CONCLUSIONS: HIF-1α testiculaire est. régulé à la hausse après inflammation induite par LPS. Contrairement à d'autres tissus, dans lesquels HIF-1α est. régulé à la hausse par activation transcriptionnelle via NF- kB, nous concluons que HIF-1α dans le testicule n'est. pas régulé à la hausse par une augmentation de Hif-1 αmRNA ou par des mécanismes NF-kB-dépendants. Les gènes de la voie hypoxie et les gènes impliqués dans le récepteur Toll-like (TLR) et dans la signalisation médiée par les cytokines comprennent des catégories fonctionnelles majeures de gènes régulés à la hausse, ce qui démontre qu'à la fois les voies de l'hypoxie et les voies classiques de l'inflammation sont impliquées dans les réponses inflammatoires du testicule.

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