scholarly journals Tissue Infiltrating Immune Cells and Endometrial Cancer Prognosis

2021 ◽  
pp. 1-8
Author(s):  
Maureen Drakes ◽  
Maureen Drakes ◽  
Swati Mehrotra ◽  
Ronald K. Potkul ◽  
Cheryl M. Czerlanis ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Immune Cells ◽  
Current Knowledge ◽  
Early Stage ◽  
Disease Onset ◽  
Cancer Prognosis ◽  
Current Therapy ◽  
Novel Therapy ◽  
Early Stage Disease ◽  
Number Of Patients

The number of patients diagnosed with endometrial cancer surpasses that of any other gynaecological cancer. This disease is usually detected early after disease onset and with current therapy 80 percent of patients with early-stage disease reach a five-year survival milestone. However, patients with advanced or recurrent disease have a grim outcome and the five-year survival rate for these patients is only about 16 percent. In several cancer types there is accumulating evidence that immune cells play a crucial role in the initiation, progression and outcome of disease. In order to provide novel and effective immunotherapeutic treatments for advanced disease endometrial cancer, an understanding of the relevance of immune cells needs to be addressed. This review briefly discusses current knowledge in the area of immune cells and how they may alter the course of endometrial cancer, as well as the implications of these cells for novel therapy and outcome.

Undifferentiated endometrial carcinoma: a National Cancer Database analysis of prognostic factors and treatment outcomes

2019 ◽  
Vol 29 (7) ◽  
pp. 1126-1133
Author(s):  
Mariam AlHilli ◽  
Paul Elson ◽  
Lisa Rybicki ◽  
Sudha Amarnath ◽  
Bin Yang ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Prognostic Factors ◽  
Adjuvant Therapy ◽  
Endometrial Carcinoma ◽  
Treatment Outcomes ◽  
Survival Data ◽  
Early Stage ◽  
National Cancer Database ◽  
Early Stage Disease ◽  
Prognostic Groups

BackgroundUndifferentiated endometrioid endometrial carcinoma of the uterus is a rare, highly aggressive, and under-recognized subtype of endometrial cancer.ObjectiveThis study evaluates survival, prognostic factors for survival, and treatment outcomes associated with undifferentiated endometrial cancer.MethodsThe National Cancer Database was queried to identify patients with undifferentiated endometrial cancer who underwent definitive primary surgical treatment. Patients with all other histologic subtypes or incomplete treatment data were excluded. Univariable and multivariable Cox proportional hazards analyses were used to determine independent prognostic factors for survival. Points for each prognostic factor were assigned from regression coefficients in the final multivariable model and summed for a total score. Recursive partitioning analysis was used to determine cut-offs in the score to identify unique prognostic groups.ResultsAmong 349 404 women diagnosed with endometrial cancer from 2004 to 2013, 3994 (1.1%) met the criteria for diagnosis of undifferentiated endometrial cancer and 3486 had survival data. Median age at diagnosis was 65 years (interquartile range (IQR) 57–74) and 58% of patients had early stage disease. Median interval from diagnosis to surgery was 3.7 weeks (IQR 2.0–5.7). Five year overall survival was 57% (standard error (SE) 1%). Stage was the strongest predictor of survival, with a 15–20% decrement in 5 year survival for each advance in stage. Stage, age, race, and presence of comorbidities were independent predictors of survival and were used to categorize patients into five prognostic groups. Adjuvant therapy was associated with improved survival across most disease stages and prognostic groups. Multimodal adjuvant therapy was superior to unimodal treatment particularly in advanced stage unfavorable and very unfavorable groups.ConclusionIn women with undifferentiated endometrial cancer, survival is primarily driven by stage. Despite the poor overall prognosis of undifferentiated endometrial cancer, multimodal adjuvant therapy is a key component of treatment.

scholarly journals Could IL-17A Be a Novel Therapeutic Target in Diabetic Nephropathy?

2020 ◽  
Vol 9 (1) ◽  
pp. 272 ◽  
Author(s):  
Carolina Lavoz ◽  
Sandra Rayego-Mateos ◽  
Macarena Orejudo ◽  
Lucas Opazo-Ríos ◽  
Vanessa Marchant ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Immune Cells ◽  
Current Knowledge ◽  
Premature Mortality ◽  
Active Role ◽  
Renal Diseases ◽  
Economic Implications ◽  
Number Of Patients ◽  
Stage Renal Disease

Chronic kidney disease has become a major medical issue in recent years due to its high prevalence worldwide, its association with premature mortality, and its social and economic implications. A number of patients gradually progress to end-stage renal disease (ESRD), requiring then dialysis and kidney transplantation. Currently, approximately 40% of patients with diabetes develop kidney disease, making it the most prevalent cause of ESRD. Thus, more effective therapies for diabetic nephropathy are needed. In preclinical studies of diabetes, anti-inflammatory therapeutic strategies have been used to protect the kidneys. Recent evidence supports that immune cells play an active role in the pathogenesis of diabetic nephropathy. Th17 immune cells and their effector cytokine IL-17A have recently emerged as promising targets in several clinical conditions, including renal diseases. Here, we review current knowledge regarding the involvement of Th17/IL-17A in the genesis of diabetic renal injury, as well as the rationale behind targeting IL-17A as an additional therapy in patients with diabetic nephropathy.

scholarly journals Endometrial Cancer: What Is New in Adjuvant and Molecularly Targeted Therapy?

2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Flora Zagouri ◽  
George Bozas ◽  
Eftichia Kafantari ◽  
Marinos Tsiatas ◽  
Nikitas Nikitas ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Metastatic Disease ◽  
Cancer Biology ◽  
Early Stage ◽  
Single Agent ◽  
Postoperative Management ◽  
Low Grade ◽  
Early Stage Disease ◽  
High Risk Factors ◽  
Staging Surgery

Endometrial cancer is the most common gynaecological cancer in western countries. Radiotherapy remains the mainstay of postoperative management, but accumulating data show that adjuvant chemotherapy may display promising results after staging surgery. The prognosis of patients with metastatic disease remains disappointing with only one-year survival. Progestins represent an effective option, especially for those patients with low-grade estrogen and/or progesterone receptor positive disease. Chemotherapy using the combination of paclitaxel, doxorubicin, and cisplatin is beneficial for patients with advanced or metastatic disease after staging surgery and potentially for patients with early-stage disease and high-risk factors. Toxicity is a point in question; however, the combination of paclitaxel with carboplatin may diminish these concerns. In women with multiple medical comorbidities, single-agent chemotherapy may be better tolerated with acceptable results. Our increased knowledge of the molecular aspects of endometrial cancer biology has paved the way for clinical research to develop novel targeted antineoplastic agents (everolimus, temsirolimus, gefitinib, erlotinib, cetuximab, trastuzumab, bevacizumab, sorafenib) as more effective and less toxic options. Continued investigation into the molecular pathways of endometrial cancer development and progression will increase our knowledge of this disease leading to the discovery of novel, superior agents.

SIENDO/ENGOT-EN5/GOG-3055: A randomized phase 3 trial of maintenance selinexor versus placebo after combination platinum-based chemotherapy in advanced or recurrent endometrial cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS5610-TPS5610
Author(s):  
Ignace Vergote ◽  
Jose Alejandro Perez-Fidalgo ◽  
Erika P. Hamilton ◽  
Toon Van Gorp ◽  
Giorgio Valabrega ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Maintenance Therapy ◽  
Nuclear Export ◽  
Early Stage ◽  
Stage Iv ◽  
Primary Therapy ◽  
Phase 3 ◽  
Primary Stage ◽  
Early Stage Disease ◽  
Platinum Based Chemotherapy

TPS5610 Background: Endometrial cancer (EC) is the most common gynecologic malignancy. Options for advanced or recurrent EC following platinum-based therapy and/or radiotherapy are limited and prognosis remains poor. Selinexor is a novel, oral selective inhibitor of nuclear export (SINE) which forces nuclear retention and activation of tumor suppressor proteins. Selinexor in combination with low dose dexamethasone is approved for relapsed/refractory multiple myeloma. In addition, selinexor monotherapy has demonstrated broad activity in other hematologic malignancies and solid tumors. In a phase 2 study, 50 mg/m2 (̃80 mg) selinexor administered twice weekly demonstrated a disease control rate ( SD ≥ 12 weeks or a PR) of 35% with 2 confirmed partial responses among 23 heavily pretreated EC patients); similar results were observed in 60 pts with platinum resistant or refractory ovarian cancer (median 5 prior regimens, ORR 8%, DCR 30%) (Vergote I et al. Gynecol Oncol 2020). In the absence of approved maintenance therapies, we conducted this study to evaluate the efficacy of selinexor compared with placebo as maintenance therapy in patients with advanced or recurrent EC following platinum-based chemotherapy. Methods: This is a multicenter, double-blind, placebo-controlled, randomized phase 3 study in patients in partial (PR) or complete remission (CR) after completing at least 12 weeks of taxane-platinum combination therapy for primary Stage IV disease and recurrent disease (i.e., relapse after primary therapy for early stage disease including surgery and/or adjuvant therapy). A total of 248 patients will be enrolled at 80 sites in Europe, North America, and Israel. Patients will be randomized in a 2:1 ratio to either maintenance therapy with 80 mg oral selinexor once weekly or placebo. Stratification factors include primary Stage IV versus first recurrence at the time of taxane-platinum therapy and disease status after chemotherapy (PR vs CR). Treatment will continue until disease progression. The primary endpoint is progression free survival (PFS) per RECIST v1.1. Secondary endpoints include disease-specific survival, overall survival, time to first subsequent therapy, time to second subsequent therapy, PFS on subsequent therapy and safety and tolerability. The study is currently open and enrolling patients. Clinical trial information: NCT03555422.

scholarly journals Molecular estimation of neurodegeneration pseudotime in older brains

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Sumit Mukherjee ◽  
Laura Heath ◽  
Christoph Preuss ◽  
Suman Jayadev ◽  
Gwenn A. Garden ◽  
...  
Keyword(s):  
Late Stage ◽  
Late Onset ◽  
Early Stage ◽  
Disease Onset ◽  
Postmortem Brain ◽  
Disease Stage ◽  
Rna Seq ◽  
Early Stage Disease ◽  
Molecular Changes ◽  
Stage Disease

AbstractThe temporal molecular changes that lead to disease onset and progression in Alzheimer’s disease (AD) are still unknown. Here we develop a temporal model for these unobserved molecular changes with a manifold learning method applied to RNA-Seq data collected from human postmortem brain samples collected within the ROS/MAP and Mayo Clinic RNA-Seq studies. We define an ordering across samples based on their similarity in gene expression and use this ordering to estimate the molecular disease stage–or disease pseudotime-for each sample. Disease pseudotime is strongly concordant with the burden of tau (Braak score, P = 1.0 × 10−5), Aβ (CERAD score, P = 1.8 × 10−5), and cognitive diagnosis (P = 3.5 × 10−7) of late-onset (LO) AD. Early stage disease pseudotime samples are enriched for controls and show changes in basic cellular functions. Late stage disease pseudotime samples are enriched for late stage AD cases and show changes in neuroinflammation and amyloid pathologic processes. We also identify a set of late stage pseudotime samples that are controls and show changes in genes enriched for protein trafficking, splicing, regulation of apoptosis, and prevention of amyloid cleavage pathways. In summary, we present a method for ordering patients along a trajectory of LOAD disease progression from brain transcriptomic data.

Therapeutic Targets and Opportunities in Endometrial Cancer: Update on Endocrine Therapy and Nonimmunotherapy Targeted Options

2020 ◽  
pp. 245-255
Author(s):  
Helen J. MacKay ◽  
Victor Rodriguez Freixinos ◽  
Gini F. Fleming
Keyword(s):  
Endometrial Cancer ◽  
Endocrine Therapy ◽  
Metastatic Disease ◽  
Early Stage ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Targeted Treatment ◽  
Early Stage Disease ◽  
New Era ◽  
Stage Disease

Worldwide, the incidence of endometrial cancer is increasing. Although the prognosis remains good for patients diagnosed with early-stage disease, for those diagnosed with recurrent or metastatic disease, options have been limited, and prognosis is short. Optimizing and identifying new well-tolerated treatments for women living with endometrial cancer is a top priority. A new era is dawning where we are starting to see the integration of clinically relevant genomic and pathologic data to inform and refine treatment strategies for women with endometrial cancer. Here, we focus on reviewing nonimmunotherapy-based targeted treatment options and emerging directions for women with endometrial cancer.

Diagnosis of Endometrial Cancer by Hysteroscopy Does Not Increase the Risk for Microscopic Extrauterine Spread in Early Stage Disease

2005 ◽  
Vol 60 (9) ◽  
pp. 579-580
Author(s):  
Guy Gutman ◽  
Benny Almog ◽  
Joseph B. Lessing ◽  
Amiram Bar-Am ◽  
Dan Grisaru
Keyword(s):  
Endometrial Cancer ◽  
Early Stage ◽  
Early Stage Disease ◽  
Stage Disease

scholarly journals MEK Pathway Inhibition Increases the Efficacy of a PI3K and HDAC Inhibitor in Endometrial Cancer Cells

2021 ◽  
Author(s):  
Konstantinos Polymeros ◽  
David S. Guttery ◽  
Salvador Macip ◽  
Esther L. Moss
Keyword(s):  
Endometrial Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Hdac Inhibitor ◽  
Early Stage ◽  
Treatment Options ◽  
Mek Inhibitor ◽  
Early Stage Disease ◽  
Disease Response

Abstract Background: Endometrial cancer (EC) is the commonest gynaecologic malignancy in many countries and its incidence is rising. Although excellent prognosis is associated with early stage disease, response to systemic treatment for metastatic or recurrent EC is often low and treatment options are limited.Aims-Methods: The aim of the study was to propose improved targeted drug treatments suitable for subsequent testing in pre-clinical models of EC. Cell proliferation assay (MTS) was used to assess viability of EC cell lines following treatment with drug inhibitors and Western blotting to explore the effect of inhibitors in molecular pathways. Results: We identified that CUDC-907, a PI3K and HDAC inhibitor, was the most effective monotherapy treatment of a panel of drugs screened in EC cells. Moreover, several combination treatments showed synergism in EC cell lines, with the most efficacious being CUDC-907 combined with the MEK inhibitor PD0325901. This indicates that simultaneous inhibition of two main oncogenic pathways, PI3K and MEK, could improve drug sensitivity in EC.Conclusions: In summary, we propose a range of targeted inhibitory drugs, alone or in combination, showing in vitro efficacy in endometrial cancer cells, which could provide novel therapeutic strategies for advanced EC.

Merkel Cell Carcinoma

2017 ◽  
Author(s):  
Giorgos Karakousis ◽  
Charles C Vining ◽  
Andrew J Sinnamon
Keyword(s):  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Current Knowledge ◽  
Early Stage ◽  
Merkel Cell Polyomavirus ◽  
High Recurrence Rate ◽  
Merkel Cell ◽  
Early Stage Disease ◽  
Large Variability ◽  
Prognostic Features

Merkel cell carcinoma (MCC) is a rare and highly aggressive carcinoma of the skin with a high recurrence rate and propensity for metastasis. It was first described in 1972 and subsequently reclassified as a neuroendocrine tumor. Merkel cells are now thought to arise from the epidermal stem cells, not neural crest progenitor cells, as originally thought, and are the only cutaneous cells that form electron-dense neurosecretory granules. Although rare, the incidence of MCC is rapidly increasing. MCC is more often than not associated with Merkel cell polyomavirus, which may be involved in the malignant transformation and pathogenesis of MCC. Mortality exceeds that of the more commonly occurring skin cancer melanoma, with an overall 5-year survival rate ranging from 30 to 64%. Large reviews have documented recurrence rates ranging from 25 to 50% for local recurrence, 52 to 59% for regional recurrence, and 34 to 36% for distant metastases. Early-stage disease can sometimes be cured with surgery and radiation. Due to the rarity of MCC, statistically significant prospective data are lacking to validate prognostic features and treatment. Therefore, recommendations are largely based on small studies, meta-analyses, and expert consensus. Moreover, no consistent molecular activator in MCC has been identified, resulting in large variability in targeted therapies used in its treatment. New therapies to treat advanced MCC, including immunotherapy, hold promise for improved outcomes in the future. This review summarizes current knowledge regarding the etiology, prognosis, and management of MCC. This review contains 6 figures, 4 tables and 52 references  Key words: Merkel cell carcinoma, Merkel cell polyomavirus, Merkel cell tactile receptor

Sign in / Sign up

Export Citation Format

Share Document