Endometrial Cancer: genetic, metabolic characteristics, therapeutic strategies and nanomedicine

2021 ◽  
Vol 28 ◽  
Author(s):  
Yuxuan Cai ◽  
Bei Wang ◽  
Wen Xu ◽  
Kai Liu ◽  
Yisong Gao ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Precancerous Lesions ◽  
Hypoxia Inducible Factor ◽  
The United States ◽  
Genetic Alterations ◽  
Therapeutic Strategies ◽  
Current Application ◽  
Female Population ◽  
Von Hippel Lindau ◽  
Metabolic Characteristics

Background: Endometrial cancer is the fourth most common malignancy in the female population worldwide. It was estimated that 65,620 new cases and 12,590 subsequent deaths occurred in 2020 in the United States. Patients with type II and advanced endometrial cancer do not respond well to the current treatments. Therefore, endometrial cancer should be better understood in order to develop more effective treatments. Objective: To provide an overview of genetic, metabolic characteristics, therapeutic strategies and current application of nanotechnology surrounding endometrial cancer. Method: Relevant articles were retrieved from Pubmed and were systematically reviewed. Results: Hypoxia-inducible factor-1 and Von Hippel-Lindau factor participated in oncogenesis and progression of endometrial cancer, and Nrf2 was associated with oncogenesis. Various genetic alterations were found in endometrial cancer. The examination of the abnormal X chromosome inactivation may help with the diagnosis of endometrial cancer and its precancerous lesions. Some absent tumor suppressor genes, activated oncogenes were revealed by the genetically modified mouse models. Disorders in glucose and lipid metabolism were found in endometrial cancer. Current therapeutic strategies focused on the HIF-1α pathway, the mTOR pathway as well as immunotherapy. Nanotechnology showed great potential in endometrial cancer’s early diagnosis, metastasis determination and treatment. Conclusion: Endometrial cancer has been understood in various aspects, but the underlying mechanisms still remain relatively unknown, which might be the source of novel diagnostic, prognostic and therapeutic targets. Nanomedicine in endometrial cancer is poorly studied, but the current researches showed great results in treating endometrial cancer. It needs further researching.

scholarly journals Emerging molecular-targeted therapies—the challenging case of endometrial cancer

2015 ◽  
Vol 1 (1) ◽  
pp. 8
Author(s):  
Ines Vasconcelos
Keyword(s):  
Endometrial Cancer ◽  
Targeted Therapies ◽  
Progressive Disease ◽  
Advanced Disease ◽  
Treatment Options ◽  
Therapy Resistance ◽  
The United States ◽  
Genetic Alterations ◽  
Persistent Disease ◽  
Disease Identification

<p>Endometrial cancer newly affects an estimated 54,870 women in the United States, being responsible for an estimated 10,170 deaths in 2015. It has demonstrated to harbor a complex carcinogenesis process, with limited treatment options for advanced or persistent disease. Identification and targeting of genetic alterations that lead to progressive disease and therapy resistance is not only challenging, but also often does not correlate with a clinical benefit. Targeted maintenance therapies in endometrial cancer have been largely disappointing. Nonetheless, targeted personalized treatment should be the main goal of treatment of advanced disease in the future. Due to the high variety of drugs being tested in early clinical trials, it is hard to keep pace with the latest developments and ongoing trials. This review aims to summarize the latest published and ongoing trials on targeted therapies in endometrial cancer.</p>

Trends in the incidence of endometrial cancer among young women in the United States, 2001 to 2017.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5578-5578
Author(s):  
Fangjian Guo ◽  
Lyuba Levine ◽  
Abbey Berenson
Keyword(s):  
Endometrial Cancer ◽  
Young Adult ◽  
Young Women ◽  
Cancer Incidence ◽  
The United States ◽  
Adult Women ◽  
Obesity Prevalence ◽  
Young Adult Women ◽  
Female Population ◽  
The Us

5578 Background: Endometrial cancer at this time is predominantly being looked at as a disease of postmenopausal population. Increased obesity has been identified as an important risk factor for endometrial cancer. An overall increase incidence of endometrial hyperplasia and endometrial carcinoma in obese premenopausal women has been reported. A close examination of the relationship between trends in endometrial cancer incidence and obesity prevalence in young women will provide important information for prevention and early screening of the disease and its precursors. This study was to assess current trends in endometrial cancer incidence in women ages 20-29 and 30-39 years in relationship to obesity in the US. Methods: We used data on US adult women 20-39 years old from the National Program for Cancer Registries and Surveillance, Epidemiology, and End Results Incidence–U.S. Cancer Statistics 2001–2017 database. This database covered essentially all young female population between 2001 and 2017 in the US (Puerto Rico not included). Incidence was age adjusted to the 2020 U.S. standard population. We also examined the trends in obesity prevalence among females 18-34 years old using data from the National Health and Nutrition Examination Survey (NHANES) III and NHANES 1999-2014. Results: There were 24,446 cases of endometrial cancer among young adult women aged 20-39 years during 2001-2017. Endometrial cancer incidence increased from 0.6 per 100,000 in 2001 to 1.2 per 100,000 in 2017 (APC 3.6, 95% CI 2.9-4.4) among young women 20-29 years old, and increased from 4.6 per 100,000 in 2001 to 7.5 per 100,000 in 2017 (APC 3.0, 95% CI 2.7-3.3) among women 30-39 years old. Obesity prevalence also increased significantly from 1988-2014 among females 18-34 years old. Incidence of endometrial cancer and obesity prevalence were both higher in Hispanics than in other racial/ethnic groups. Conclusions: The significant increasing incidence in endometrial cancer among young adult women is in accordance with the concurrent increasing prevalence in obesity in young girls and women in the US. This indicates that endometrial cancer screening might need to be considered at much earlier age among patients with abnormal bleeding and certain ethnic populations.

scholarly journals VHLGenetic Alteration in CCRCC Does Not Determine De-Regulation of HIF, CAIX, hnRNP A2/B1 and Osteopontin

2010 ◽  
Vol 33 (3-4) ◽  
pp. 121-132 ◽  
Author(s):  
Michelle J. Nyhan ◽  
Shereen M. El Mashad ◽  
Tracey R. O’Donovan ◽  
Sarfraz Ahmad ◽  
Chris Collins ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Suppressor Gene ◽  
Genetic Alterations ◽  
Tumour Suppressor Gene ◽  
Cell Renal Cell Carcinoma ◽  
Protein Targets ◽  
Renal Carcinogenesis ◽  
Von Hippel Lindau ◽  
The Impact

Background: von Hippel–Lindau (VHL) tumour suppressor gene inactivation is associated with clear cell renal cell carcinoma (CCRCC) development. The VHL protein (pVHL) has been proposed to regulate the expression of several proteins including Hypoxia Inducible Factor-α (HIF-α), carbonic anhydrase (CA)IX, heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 and osteopontin. pVHL has been characterized in vitro, however, clinical studies are limited. We evaluated the impact of VHL genetic alterations on the expression of several pVHL protein targets in paired normal and tumor tissue.Methods: TheVHLgene was sequenced in 23 CCRCC patients andVHLtranscript levels were evaluated by real-time RT-PCR. Expression of pVHL’s protein targets were determined by Western blotting in 17 paired patient samples.Results: VHL genetic alterations were identified in 43.5% (10/23) of CCRCCs. HIF-1α, HIF-2α and CAIX were up-regulated in 88.2% (15/17), 100% (17/17) and 88.2% (15/17) of tumors respectively and their expression is independent ofVHLstatus. hnRNP A2/B1 and osteopontin expression was variable in CCRCCs and had no association withVHLgenetic status.Conclusion: As expression of these proposed pVHL targets can be achieved independently ofVHLmutation (and possibly by hypoxia alone), these data suggests that other pVHL targets may be more crucial in renal carcinogenesis.

The shift from inpatient to outpatient hysterectomy for endometrial cancer in the United States: trends, enabling factors, cost, and safety

2021 ◽  
pp. ijgc-2020-002192
Author(s):  
Serena Cappuccio ◽  
Yanli Li ◽  
Chao Song ◽  
Emeline Liu ◽  
Gretchen Glaser ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Abdominal Hysterectomy ◽  
The United States ◽  
Inpatient Setting ◽  
Significant Shift ◽  
Robotic Hysterectomy ◽  
Post Discharge ◽  
Enabling Factors ◽  
Healthcare Database ◽  
The Impact

ObjectiveTo evaluate trends in outpatient versus inpatient hysterectomy for endometrial cancer and assess enabling factors, cost and safety.MethodsIn this retrospective cohort study, patients aged 18 years or older who underwent hysterectomy for endometrial cancer between January 2008 and September 2015 were identified in the Premier Healthcare Database. The surgical approach for hysterectomy was classified as open/abdominal, vaginal, laparoscopic or robotic assisted. We described trends in surgical setting, perioperative costs and safety. The impact of patient, provider and hospital characteristics on outpatient migration was assessed using multivariate logistic regression.ResultsWe identified 41 246 patients who met inclusion criteria. During the time period studied, we observed a 41.3% shift from inpatient to outpatient hysterectomy (p<0.0001), an increase in robotic hysterectomy, and a decrease in abdominal hysterectomy. The robotic hysterectomy approach, more recent procedure (year), and mid-sized hospital were factors that enabled outpatient hysterectomies; while abdominal hysterectomy, older age, Medicare insurance, black ethnicity, higher number of comorbidities, and concomitant procedures were associated with an inpatient setting. The shift towards outpatient hysterectomy led to a $2500 savings per case during the study period, in parallel to the increased robotic hysterectomy rates (p<0.001). The post-discharge 30-day readmission and complications rate after outpatient hysterectomy remained stable at around 2%.ConclusionsA significant shift from inpatient to outpatient setting was observed for hysterectomies performed for endometrial cancer over time. Minimally invasive surgery, particularly the robotic approach, facilitated this migration, preserving clinical outcomes and leading to reduction in costs.

scholarly journals A small molecule HIF-1α stabilizer that accelerates diabetic wound healing

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Guodong Li ◽  
Chung-Nga Ko ◽  
Dan Li ◽  
Chao Yang ◽  
Wanhe Wang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Small Molecule ◽  
Hypoxia Inducible Factor ◽  
Diabetic Patients ◽  
Diabetic Mice ◽  
Impaired Wound Healing ◽  
Von Hippel Lindau ◽  
Design And Synthesis

AbstractImpaired wound healing and ulcer complications are a leading cause of death in diabetic patients. In this study, we report the design and synthesis of a cyclometalated iridium(III) metal complex 1a as a stabilizer of hypoxia-inducible factor-1α (HIF-1α). In vitro biophysical and cellular analyses demonstrate that this compound binds to Von Hippel-Lindau (VHL) and inhibits the VHL–HIF-1α interaction. Furthermore, the compound accumulates HIF-1α levels in cellulo and activates HIF-1α mediated gene expression, including VEGF, GLUT1, and EPO. In in vivo mouse models, the compound significantly accelerates wound closure in both normal and diabetic mice, with a greater effect being observed in the diabetic group. We also demonstrate that HIF-1α driven genes related to wound healing (i.e. HSP-90, VEGFR-1, SDF-1, SCF, and Tie-2) are increased in the wound tissue of 1a-treated diabetic mice (including, db/db, HFD/STZ and STZ models). Our study demonstrates a small molecule stabilizer of HIF-1α as a promising therapeutic agent for wound healing, and, more importantly, validates the feasibility of treating diabetic wounds by blocking the VHL and HIF-1α interaction.

scholarly journals Hypoxic tumor microenvironment: Implications for cancer therapy

2020 ◽  
Vol 245 (13) ◽  
pp. 1073-1086
Author(s):  
Sukanya Roy ◽  
Subhashree Kumaravel ◽  
Ankith Sharma ◽  
Camille L Duran ◽  
Kayla J Bayless ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Metabolic Regulation ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Tumor Vasculature ◽  
Therapeutic Strategies ◽  
Therapeutic Resistance ◽  
Low Oxygen ◽  
Cancer Types

Hypoxia or low oxygen concentration in tumor microenvironment has widespread effects ranging from altered angiogenesis and lymphangiogenesis, tumor metabolism, growth, and therapeutic resistance in different cancer types. A large number of these effects are mediated by the transcription factor hypoxia inducible factor 1⍺ (HIF-1⍺) which is activated by hypoxia. HIF1⍺ induces glycolytic genes and reduces mitochondrial respiration rate in hypoxic tumoral regions through modulation of various cells in tumor microenvironment like cancer-associated fibroblasts. Immune evasion driven by HIF-1⍺ further contributes to enhanced survival of cancer cells. By altering drug target expression, metabolic regulation, and oxygen consumption, hypoxia leads to enhanced growth and survival of cancer cells. Tumor cells in hypoxic conditions thus attain aggressive phenotypes and become resistant to chemo- and radio- therapies resulting in higher mortality. While a number of new therapeutic strategies have succeeded in targeting hypoxia, a significant improvement of these needs a more detailed understanding of the various effects and molecular mechanisms regulated by hypoxia and its effects on modulation of the tumor vasculature. This review focuses on the chief hypoxia-driven molecular mechanisms and their impact on therapeutic resistance in tumors that drive an aggressive phenotype. Impact statement Hypoxia contributes to tumor aggressiveness and promotes growth of many solid tumors that are often resistant to conventional therapies. In order to achieve successful therapeutic strategies targeting different cancer types, it is necessary to understand the molecular mechanisms and signaling pathways that are induced by hypoxia. Aberrant tumor vasculature and alterations in cellular metabolism and drug resistance due to hypoxia further confound this problem. This review focuses on the implications of hypoxia in an inflammatory TME and its impact on the signaling and metabolic pathways regulating growth and progression of cancer, along with changes in lymphangiogenic and angiogenic mechanisms. Finally, the overarching role of hypoxia in mediating therapeutic resistance in cancers is discussed.

“I Don’t Know and I Don’t Want to Know”: A Qualitative Examination of Older African American Women’s Knowledge and Experiences With HIV

2018 ◽  
Vol 44 (7) ◽  
pp. 644-666 ◽  
Author(s):  
Faye Z. Belgrave ◽  
Sarah J. Javier ◽  
Deborah Butler ◽  
Chelsie Dunn ◽  
Joann Richardson ◽  
...  
Keyword(s):  
African American ◽  
African American Women ◽  
Black Church ◽  
The United States ◽  
Sociocultural Factors ◽  
Hiv Knowledge ◽  
Female Population ◽  
American Women ◽  
Heterosexual Women ◽  
Older African American Women

While older African American women (e.g., aged 50 years and older) comprise only 11% of the female population in the United States, they account for 50% of HIV diagnoses among women in this age group. Unique sociocultural factors, including a lack of HIV knowledge and stigma, contribute to HIV risk among older African American women. The goal of this qualitative study was to obtain a nuanced perspective from older African American women about HIV knowledge and experiences with HIV using the framework of intersectionality theory. Focus groups were conducted with 35 African American women who were 50 years and older, nonpartnered, and heterosexual. Women were asked what they knew about HIV and if they thought older women were at risk for HIV. A thematic analysis using NVivo 11 yielded two central themes and three subthemes: HIV knowledge, including experiential knowledge, superficial knowledge, and no knowledge, and stigma around HIV in the Black church. Implications for developing HIV prevention programs and testing messages are discussed.

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