scholarly journals Ubiquitination and Deubiquitination in Melanoma Research and Clinically Relevant Outcomes

Author(s):  
Jia Guo ◽  
Jianglin Zhang

Malignant melanoma is one of the most invasive tumors with increasing mortality, low overall survival rates and limited effective therapeutic strategies. Ubiquitination is a post-translational protein modification, which is regulated by a series of ubiquitination-associated enzymes. Ubiquitination plays a critical role in diverse pathophysiological activities of cellular and participates in the pathogenesis of various cancers, including melanoma. This study aims to provide a conclusive of ubiquitination and deubiquitination, and their potential clinical application value in melanoma in the following aspects: melanoma pathogenesis-related components and processes in the ubuiquitin-proteasome system (UPS), ubiquitination in melanoma immunological microenvironment modulation, ubiquitination of key transcription factors in melanoma and melanoma therapeutic strategy via targeting the UPS.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e24075-e24075
Author(s):  
Tao Li

e24075 Background: The prognostic nutrition index (PNI) has been shown to have prognostic value in several common cancers. We explore its clinical application value in the prognosis of patients with esophageal squamous cell carcinoma (ESCC) undergoing radical chemoradiotherapy (CRT) or radiotherapy. Methods: Overall, 193 patients with ESCC who received radiotherapy with or without chemotherapy at Sichuan Cancer Hospital from March 20, 2012 to December 25, 2017 were retrospectively analyzed. Based on serum measurements before treatment, PNI at ESCC recurrence was calculated as albumin (g/L) + 5 × total lymphocyte count. Kaplan-Meier method and Cox proportional regression model were used to analyze the relationship between PNI and overall survival (OS). Results: The PNI of 193 ESCC patients was 49.01 ± 4.68. The optimal cutoff value of PNI was calculated to be 47.975. The patients were divided into a low PNI group (<47.975) and a high PNI group (≥47.975). The median OS for the entire group was 22.37 months. The median OS of patients in the high PNI group (PNI ≥ 47.975) and low PNI group (PNI <47.975) were 32.63 months and 15.4 months, respectively. The 3-year overall survival rates were 47.5% and 32.2%, and 5-year overall survival rates were 37.7% and 16.8%, respectively, and the differences were statistically significant (P = 0.001). Multivariate analysis showed that tumor length (P = 0.019), synchronous chemotherapy (P = 0.009), and PNI (P = 0.003) were independent prognostic factors affecting the prognosis of patients in ESCC treated with radical CRT or radiotherapy. Conclusions: The calculation of PNI value is simple, reliable and repeatable, which can improve the accuracy of patients' prognosis. And it needs to be further confirmed by the prospective study of large sample size. Keywords: Esophageal squamous cell carcinoma, chemoradiotherapy, prognostic nutritional index, prognosis.



BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhihao Lv ◽  
Yuqi Liang ◽  
Huaxi Liu ◽  
Delong Mo

Abstract Background It remains controversial whether patients with Stage II colon cancer would benefit from chemotherapy after radical surgery. This study aims to assess the real effectiveness of chemotherapy in patients with stage II colon cancer undergoing radical surgery and to construct survival prediction models to predict the survival benefits of chemotherapy. Methods Data for stage II colon cancer patients with radical surgery were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (1:1) was performed according to receive or not receive chemotherapy. Competitive risk regression models were used to assess colon cancer cause-specific death (CSD) and non-colon cancer cause-specific death (NCSD). Survival prediction nomograms were constructed to predict overall survival (OS) and colon cancer cause-specific survival (CSS). The predictive abilities of the constructed models were evaluated by the concordance indexes (C-indexes) and calibration curves. Results A total of 25,110 patients were identified, 21.7% received chemotherapy, and 78.3% were without chemotherapy. A total of 10,916 patients were extracted after propensity score matching. The estimated 3-year overall survival rates of chemotherapy were 0.7% higher than non- chemotherapy. The estimated 5-year and 10-year overall survival rates of non-chemotherapy were 1.3 and 2.1% higher than chemotherapy, respectively. Survival prediction models showed good discrimination (the C-indexes between 0.582 and 0.757) and excellent calibration. Conclusions Chemotherapy improves the short-term (43 months) survival benefit of stage II colon cancer patients who received radical surgery. Survival prediction models can be used to predict OS and CSS of patients receiving chemotherapy as well as OS and CSS of patients not receiving chemotherapy and to make individualized treatment recommendations for stage II colon cancer patients who received radical surgery.



2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yuyun Wu ◽  
Ningbo Hao ◽  
Suming Wang ◽  
Xin Yang ◽  
Yufeng Xiao ◽  
...  

Gastric cancer (GC) is one of the most common malignancies worldwide, and the tumor metastasis leads to poor outcomes of GC patients. Long noncoding RNAs (lncRNAs) have emerged as new regulatory molecules that play a crucial role in tumor metastasis. However, the biological function and underlying mechanism of numerous lncRNAs in GC metastasis remain largely unclear. Here, we report a novel lncRNA, lnc-TLN2-4:1, whose expression is decreased in GC tissue versus matched normal tissue, and its low expression is involved in the lymph node and distant metastases of GC, as well as poor overall survival rates of GC patients. We further found that lnc-TLN2-4:1 inhibits the ability of GC cells to migrate and invade but does not influence GC cell proliferation and confirmed that lnc-TLN2-4:1 is mainly located in the cytoplasm of GC cells. We then found that lnc-TLN2-4:1 increases the mRNA and protein expression of TLN2 in GC cells and there is a positive correlation between the expression of lnc-TLN2-4:1 and TLN2 mRNA in GC tissue. Collectively, we identified a novel lncRNA, lnc-TLN2-4:1, in GC, where lnc-TLN2-4:1 represses cell migration and invasion. The low expression of lnc-TLN2-4:1 is associated with poor overall survival rates of GC patients. These suggest that lnc-TLN2-4:1 may be a tumor suppressor during GC metastasis.



2019 ◽  
Author(s):  
Lee Sing Chet ◽  
Siti Azrin Ab Hamid ◽  
Norsa'adah Bachok ◽  
Suresh Kumar Chidambaram

Abstract Background: It is well established that antiretroviral therapy (ART) is beneficial in reducing the mortality among patients with human immunodeficiency virus (HIV). In Malaysia, there is lack of study and information regarding the overall survival rates and prognostic factors for survival in HIV-infected adults treated with ART. Therefore, this study aimed to assess and compare the survival rates as well as to identify the prognostic factors for survival among HIV adults in Malaysia.Methods: A retrospective cohort study was conducted by reviewing the medical records of HIV patients who started ART between year 2007 and 2016 at a tertiary referral hospital in Malaysia. ART-naive adults aged 15 years and above were included and those who were transferred out were excluded. After applying inclusion and exclusion criteria, there were 339 cases eligible in this study. Systematic sampling method was applied. Kaplan Meier survival curve and log-rank test were used to compare the overall survival rates. Cox proportional hazards regression was applied to determine the prognostic factors for survival.Results: The estimated overall survival rates were 95.9%, 93.8%, 90.4%, 84.9%, and 72.8% at 6 months, 1 year, 3 years, 5 years and 10 years, respectively. The overall survival rates were significantly different according to age group (p<0.001), employment status (p<0.001), transmission mode (p=0.003), and history of illicit drug use (p=0.017), baseline CD4 cell count (p<0.001), baseline haemoglobin level (p<0.001), tuberculosis co-infection (p<0.001), hepatitis co-infection (p=0.008), first NRTI (p<0.001) and history of defaults (p=0.021). Based on multiple Cox regression, patients who were anaemic had 3.76 times (95% CI: 1.97, 7.18; p<0.001) higher hazard of death than their non-anaemic counterparts. The hazard risk was 2.09 times (95% CI: 1.10, 3.96; p=0.024) higher among HIV patients co-infected with tuberculosis compared to those who were not. Conclusion: Overall survival rates were higher than low-income countries but lower than in high-income countries, and comparable with middle-income countries. Low baseline haemoglobin level and tuberculosis co-infection were strong prognostic factors for HIV survival



Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4022-4022
Author(s):  
Cesar Gentille Sanchez ◽  
Joe Ensor ◽  
Akshjot Puri ◽  
Jasleen K. Randhawa ◽  
Shilpan S. Shah ◽  
...  

Introduction Primary cutaneous anaplastic large-cell lymphoma (PCALCL) is a rare T-cell lymphoma that presents as a solitary or grouped nodules. It is characterized by anaplastic-appearing cells that are usually ALK negative but have high expression of CD30. There is paucity of epidemiologic data on PCALCL. A prior analysis of the Surveillance, Epidemiology, and End Results (SEER) database by Yu et al. reported only 157 cases from 1973 to 2004. We are presenting an analysis of the patients diagnosed with PCALCL after 2004. Methods We used the SEER database to retrospectively identify patients diagnosed with PCALCL from 2005 to 2016. The database collects data from cancer registries covering approximately 26% of the US population and was used to estimate frequencies and overall incidence rate. Survival was analyzed using the Kaplan-Meier method and log-rank tests were used to compare survival distributions. We assessed the effect of primary skin site (head and neck) and increasing age on survival as they were suggestive of decreased overall survival on multivariate analysis of the 1973-2004 cohort. P < 0.05 was considered statistically significant for all analysis. Results There were 501 cases of PCALCL recorded from 2005 to 2016. Median follow-up was 52 months. The overall incidence rate was found to be 0.12/1,000,000 age adjusted to the 2000 US standard population. More than 50% of the cases were diagnosed after 2010. The median age at diagnosis was 61 years (2-97 years). It was seen most frequently in White (72.9%) patients followed by Hispanic (10.2%) and Black (9.4%) patients. The male to female ratio was 1.42. The most common primary sites affected were the skin of the lower limbs and hip (26.4%) and head and neck (21.3%). A 33.4% of patients required treatment which was mainly excisional (1 patient required amputation). Notably, PCALCL was diagnosed as a second or third malignancy in 19.2% of cases. Overall survival rates at 5 years and 10 years were found to be 80.6% (95% CI: 76.3%, 84.3%) and 61.5% (95% CI: 54.1%, 68.1%) respectively. Age greater than 60 years old was significantly associated with a lower survival (89.7% vs 54.4%, p<0.0001). Survival was not significantly different if head and neck was the site of the primary lesion (64.2% vs 60.8%, p = 0.4371). Conclusion Our analysis of the SEER database for PCALCL is the largest done to our knowledge. Although the number of cases has almost tripled since 2005, it is still a rare type of cutaneous T-cell lymphoma. Lower extremities and hips are the most frequent primary skin site. Only a third of the patients required treatment with overall survival rates of more than 80% by 5 years. Older age (more than 60 years old) is associated with a worse outcome. Head and neck as the primary skin site does not appear to be associated to lower survival as previously thought. Disclosures No relevant conflicts of interest to declare.



2021 ◽  
Vol 1 (2) ◽  
pp. 35-42
Author(s):  
YURIKA NOGUCHI ◽  
NORIYOSHI IRIYAMA ◽  
HIROMICHI TAKAHASHI ◽  
YOSHIHITO UCHINO ◽  
MASARU NAKAGAWA ◽  
...  

Background/Aim: Here, we investigated whether bortezomib as a maintenance therapy affected outcomes in transplant-ineligible patients with multiple myeloma (MM). Patients and Methods: Following induction therapy with bortezomib, maintenance therapy with bortezomib (1.3 mg/m2) and dexamethasone (20 mg) was administered once or twice every 4 weeks until disease progression. The endpoints of this study were time to next treatment and overall survival. Results: Seventy-six newly diagnosed, transplant-ineligible patients were treated with a bortezomib-based regimen; 28 discontinued induction therapy, 27 did not receive maintenance therapy after induction therapy (the non-maintenance group), and 21 did (the maintenance group). In the three groups, the median times to the next required treatment were 3, 14, and 37 months, respectively. The 3-year overall survival rates were 55%, 69%, and 85%, respectively. There were no significant differences in patient characteristics between the non-maintenance and maintenance groups, except for poorer estimated glomerular filtration rates in the maintenance group. Conclusion: Bortezomib maintenance therapy may be a useful option for transplant-ineligible patients with MM.



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