scholarly journals Understanding the impact of sex and stage differences on melanoma cancer patient survival: a SEER-based study

Author(s):  
Aiden J. Smith ◽  
Paul C. Lambert ◽  
Mark J. Rutherford
Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2907
Author(s):  
Maral Jamshidi ◽  
Rainer Fagerholm ◽  
Taru A. Muranen ◽  
Sippy Kaur ◽  
Swapnil Potdar ◽  
...  

Deregulated miRNA expression has been suggested in several stages of breast cancer pathogenesis. We have studied the miR-30 family, in particular miR-30d, in relation to breast cancer patient survival and treatment outcomes. With tumor specimens from 1238 breast cancer patients, we analyzed the association of miR-30d expression with tumor characteristics with the 5-year occurrence of breast cancer-specific death or distant metastasis (BDDM), and with 10-year breast cancer survival (BCS). We conducted a two-stage drug-screen to investigate the impact of miR-30 family members (miR-30a-30e) on sensitivity to doxorubicin and lapatinib in six breast cancer cell lines HCC1937, HCC1954, MDA-MB-361, MCF7, MDA-MB-436 and CAL-120, using drug sensitivity scores (DSS) to compare the miR-30 family mimics to their specific inhibitors. The study was complemented with Ingenuity Pathway Analysis (IPA) with the METABRIC data. We found that while high miR-30d expression is typical for aggressive tumors, it predicts better metastasis-free (pBDDM = 0.035, HR = 0.63, 95% CI = 0.4–0.9) and breast cancer-specific survival (pBCS = 0.018, HR = 0.61, 95% CI = 0.4–0.9), especially in HER2-positive (pBDDM = 0.0009), ER-negative (pBDDM = 0.003), p53-positive (pBDDM = 0.011), and highly proliferating (pBDDM = 0.0004) subgroups, and after adjuvant chemotherapy (pBDDM = 0.035). MiR-30d predicted survival independently of standard prognostic markers (pBDDM = 0.0004). In the drug-screening test, the miR-30 family sensitized the HER2-positive HCC1954 cell line to lapatinib (p < 10–2) and HCC1937, MDA-MB-361, MDA-MB-436 and CAL120 to doxorubicin (p < 10–4) with an opposite impact on MCF7. According to the pathway analysis, the miR-30 family has a suppressive effect on cell motility and metastasis in breast cancer. Our results suggest prognostic and predictive potential for the miR-30 family, which warrants further investigation.


Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3045
Author(s):  
Euiyoung Oh ◽  
Jun-Hyeong Kim ◽  
JungIn Um ◽  
Da-Woon Jung ◽  
Darren R. Williams ◽  
...  

The relationship between expression of aging-related genes in normal tissues and cancer patient survival has not been assessed. We developed a genome-wide transcriptomic analysis approach for normal tissues adjacent to the tumor to identify aging-related transcripts associated with survival outcome, and applied it to 12 cancer types. As a result, five aging-related genes (DUSP22, MAPK14, MAPKAPK3, STAT1, and VCP) in normal tissues were found to be significantly associated with a worse survival outcome in patients with renal cell carcinoma (RCC). This computational approach was investigated using nontumorigenic immune cells purified from young and aged mice. Aged immune cells showed upregulated expression of all five aging-related genes and promoted RCC invasion compared to young immune cells. Further studies revealed DUSP22 as a regulator and druggable target of metastasis. DUSP22 gene knockdown reduced RCC invasion and the small molecule inhibitor BML-260 prevented RCC dissemination in a tumor/immune cell xenograft model. Overall, these results demonstrate that deciphering the relationship between aging-related gene expression in normal tissues and cancer patient survival can provide new prognostic markers, regulators of tumorigenesis and novel targets for drug development.


2021 ◽  
Vol 11 (2) ◽  
pp. 90
Author(s):  
Chih-Yang Hsiao ◽  
Ming-Chih Ho ◽  
Cheng-Maw Ho ◽  
Yao-Ming Wu ◽  
Po-Huang Lee ◽  
...  

Tacrolimus is the most widely used immunosuppressant in liver transplant (LT) patients. However, the ideal long-term target level for these patients is unknown. This retrospective study aimed to investigate the impact of tacrolimus blood concentration five years after LT on long-term patient survival outcomes in adult LT recipients. Patients who underwent LT between January 2004 and July 2014 at a tertiary medical center were included in this study (n = 189). The mean tacrolimus blood concentrations of each patient during the fifth year after LT were recorded and the overall survival rate was determined. A multivariate analysis of factors associated with long-term survival was conducted using a Cox’s model. The median follow-up period was 9.63 years, and 144 patients (76.2%) underwent live donor LT. Sixteen patients died within 5 years of LT. In the Cox’s model, patients with a mean tacrolimus blood trough level of 4.6–10.2 ng/mL had significantly better long-term survival than those with a mean tacrolimus blood trough level outside this range (estimated hazard ratio = 4.76; 95% confidence interval: 1.34–16.9, p = 0.016). Therefore, a tacrolimus level no lower than 4.6 ng/mL would be recommended in adult LT patients.


Author(s):  
Claudius Speer ◽  
Christine Altenmüller-Walther ◽  
Jan Splitthoff ◽  
Christian Nusshag ◽  
Florian Kälble ◽  
...  

AbstractTo study the impact of glucocorticoid maintenance dose and treatment duration on outcomes in patients with AAV (ANCA-associated vasculitis) with emphasis on infectious complications. A total of 130 AAV patients from two German vasculitis centers diagnosed between August 2004 and January 2019 treated with cyclophosphamide and glucocorticoids for induction therapy and glucocorticoids for maintenance therapy were retrospectively enrolled. We investigated the influence of glucocorticoid maintenance therapy on patient survival, time to relapse, kidney function, infectious complications and irreversible physical damage. The patients were divided into the following groups: patients treated according to the predefined reduction scheme (< 7.5 mg) or patients treated with glucocorticoids ≥ 7.5 mg after 6 months. Compared to patients receiving < 7.5 mg glucocorticoids after 6 months, patients receiving $$\ge $$ ≥ 7.5 mg had an increased rate of infectious episodes per patient (1.7 vs. 0.6; p < 0.001), including urinary tract infection (p = 0.007), pneumonia (p = 0.003), opportunistic pneumonia (p = 0.022) and sepsis (p = 0.008). Especially pneumonia during the first 24 months after disease onset [hazard ratio, 3.0 (95% CI 1.5 − 6.1)] led to more deaths from infection (p = 0.034). Glucocorticoid maintenance therapy after 6 months had no impact on relapse rate or patient survival and decline in kidney function was comparable. Glucocorticoid maintenance therapy with $$\ge $$ ≥ 7.5 mg after 6 months is associated with more severe infectious complications leading to an increased frequency of deaths from infection. Glucocorticoid maintenance therapy has no effect on time to relapse or patient survival and should therefore be critically revised throughout the aftercare of AAV patients.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Kazuaki Okino ◽  
Keita Yamazaki ◽  
Keiichiro Okada ◽  
Keiji Fujimoto ◽  
HIROKI ADACHI ◽  
...  

Abstract Background and Aims The impact of hepatitis C virus (HCV) infection on patient survival after renal transplantation was worse. Previously, we found that continuous HCV infection was a significant independent risk factor for actuarial survival (especially at ≥20 years after the transplant procedure) among Japanese renal allograft recipients. This study evaluates the impact of HCV and of the new direct acting antivirals (DAAs) on patient outcomes in renal allograft recipients. Method We studied 46 cases (28 males, 18 females; 37 living-donor cases, 9 deceased-donor cases; mean follow-up period 305 months ranging from 2 to 420 months) out of the 315 renal transplanted patients who underwent the first renal transplantation in Kanazawa Medical University since 1974. They had antibodies against HCV: 11 were positive for HCV RNA and received DAAs (Group A, all of them genotype 1b); 27 were HCV RNA positive and did not receive any treatment (Group B); 8 were negative for HCV RNA (Group C) (Fig.1). Results All Group A patients had HCV RNA negativity after 2-12 weeks of treatment started, and 11 (100%) achieved a sustained virological response (SVR) at 24 weeks. All of them had no adverse effects by the use of DAAs. In this cohort, no patients in Group A died. On the other hand, 15 (55.5%) of 27 in Group B and 3 (37.5%) of 8 in Group C died. Causes of death among Group B were liver cirrhosis (5 cases), hepatocellular carcinoma (2 case), infections complicated with chronic hepatitis (6 cases) in chronic phase, fibrosing cholestatic hepatitis due to HCV (1 case) after surgery, and cardiovascular disease (1 case). The patient survival rate was significantly higher in Group A patients who received DAAs by Kaplan- Meier life table method (Log Rank test, Kay-square 11.7, p=0.004) (Fig.2). Conclusion Our results support the notion that continuous HCV infection was a harmful and that new DAAs were efficient and safe to treat HCV infection after renal transplantation.


F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2893 ◽  
Author(s):  
Rossana Rosa ◽  
Jose F. Suarez ◽  
Marco A. Lorio ◽  
Michele I. Morris ◽  
Lilian M. Abbo ◽  
...  

Background: Antiretroviral therapy (ART) poses challenging drug-drug interactions with immunosuppressant agents in transplant recipients.  We aimed to determine the impact of specific antiretroviral regimens in clinical outcomes of HIV+ kidney transplant recipients. Methods: A single-center, retrospective cohort study was conducted at a large academic center. Subjects included 58 HIV- to HIV+ adult, first-time kidney transplant patients. The main intervention was ART regimen used after transplantation.  The main outcomes assessed at one- and three-years were: patient survival, death-censored graft survival, and biopsy-proven acute rejection; we also assessed serious infections within the first six months post-transplant. Results: Patient and graft survival at three years were both 90% for the entire cohort. Patients receiving protease inhibitor (PI)-containing regimens had lower patient survival at one and three years than patients receiving PI-sparing regimens: 85% vs. 100% (p=0.06) and 82% vs. 100% (p=0.03), respectively. Patients who received PI-containing regimens had twelve times higher odds of death at 3 years compared to patients who were not exposed to PIs (odds ratio, 12.05; 95% confidence interval, 1.31-1602; p=0.02).  Three-year death-censored graft survival was lower in patients receiving PI vs. patients on PI-sparing regimens (82 vs 100%, p=0.03). Patients receiving integrase strand transfer inhibitors-containing regimens had higher 3-year graft survival. There were no differences in the incidence of acute rejection by ART regimen. Individuals receiving PIs had a higher incidence of serious infections compared to those on PI-sparing regimens (39 vs. 8%, p=0.01). Conclusions: PI-containing ART regimens are associated with adverse outcomes in HIV+ kidney transplant recipients.


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