Chronic hepatitis C virus (HCV) infection is increasingly observed in patients with renal disease. With the introduction of glecaprevir/pibrentasvir (GLE/PIB) as a pan-genotype therapy for HCV, ...treatment efficacy is expected to rise.
This retrospective study evaluated the efficacy and safety of GLE/PIB treatment in adults with HCV infection and end-stage renal disease (ESRD). The primary end point was sustained virological response (SVR) observed 12 weeks after completed treatment.
We enrolled 235 patients, including 44 patients with ESRD. Median age was 60 years, and 48% were males. Twenty-two percent had cirrhosis. HCV genotypes 1 (43%) and 2 (41%) were the most common. The overall SVR rate was 96.6%. Patients with ESRD were older than those without (67.6 years vs 58.3 years, p < 0.001) and trended toward having a higher prevalence of cirrhosis (32% vs 19%, p = 0.071). A significant proportion of patients with ESRD complained of skin itching during treatment (61% vs 26%, p < 0.001), and the SVR rate were similar between these two groups (95.45% vs 96.86%, p = 0.644).
Despite a higher rate of pruritus among patients with ESRD, GLE/PIB-based therapy achieved similarly high SVR rates among patients with and without ESRD.
In recent decades, chemotherapies targeting apoptosis have emerged and demonstrated remarkable achievements. However, emerging evidence has shown that chemoresistance is mediated by impairing or ...bypassing apoptotic cell death. Several novel types of programmed cell death, such as ferroptosis, necroptosis, and pyroptosis, have recently been reported to play significant roles in the modulation of cancer progression and are considered a promising strategy for cancer treatment. Thus, the switch between apoptosis and pyroptosis is also discussed. Cancer immunotherapy has gained increasing attention due to breakthroughs in immune checkpoint inhibitors; moreover, ferroptosis, necroptosis, and pyroptosis are highly correlated with the modulation of immunity in the tumor microenvironment. Compared with necroptosis and ferroptosis, pyroptosis is the primary mechanism for host defense and is crucial for bridging innate and adaptive immunity. Furthermore, recent evidence has demonstrated that pyroptosis exerts benefits on cancer immunotherapies, including immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell therapy (CAR-T). Hence, in this review, we elucidate the role of pyroptosis in cancer progression and the modulation of immunity. We also summarize the potential small molecules and nanomaterials that target pyroptotic cell death mechanisms and their therapeutic effects on cancer.
Sol–gel thin films of amorphous LaNbO
x
(LNO) were prepared to study the bipolar resistive switching (BRS) properties of Metal/LNO/ITO devices. We investigated the influences of film thickness, top ...electrode, annealing temperature, post-metal annealing (PMA), and bilayer structure on the resistive switching (RS) characteristics. In comparison to the as-deposited LNO thin film devices, the PMA-treated devices demonstrated better RS characteristics, with lower set/reset voltages (V
Set
/V
Reset
= − 2.26V/0.9V), longer switching cycles (2466 cycles), and a > 10
1
R
on
/R
off
ratio. Furthermore, at 85 °C, the retention time exceeded 10
4
s, similar to the retention time at room temperature, indicating that random access memory (RRAM) may effectively function over 10 years. The improvement in RS characteristics can be attributed to the formation of an AlO
x
layer between the upper electrode and the insulating layer after PMA treatment, which increases the oxygen vacancy content and facilitates Al ion diffusion. The addition of a bilayer of Al was implemented to increase the thickness of AlO
x
, thereby improving the R
on
/R
off
ratio. However, this addition also degrades the RS properties of the device. Furthermore, the space charge-limited current (SCLC) conduction mechanism dominates in the high resistance state (HRS), while ohmic conduction prevails in the low resistance state (LRS) of the devices.
Arsenic is a well-established human carcinogen and is considered a health risk worldwide, especially where groundwater is consumed as drinking water. In 2018, bladder and kidney cancers were the 14th ...and 17th leading causes of global cancer mortality, respectively. Our aim was to investigate the association between arsenic exposure, DNA damage, and the incidence of bladder and kidney cancers. A total of 788 participants aged ≥40 years were enrolled in a prospective cohort study in Taiwan between 1991 and 1994, with follow-up between 2011 and 2014. Well-water and first-morning spot urine samples were collected between 1991 and 1994 to estimate arsenic exposure, and the baseline urinary levels of 8-Oxo-2′-deoxyguanosine (8-OHdG) and N7-methylguanine (N7-MeG) were quantified to assess DNA lesions. The Cox proportional hazard model was used to estimate the effects of arsenic exposure and DNA adduct levels on the risk of bladder or kidney cancer. Urinary arsenic species were associated with significantly increased 8-OHdG and N7-MeG after adjusting for age, sex, and cigarette smoking. Only non-statistically significant mediation effects of 8-OHdG were observed. In a fully adjusted Cox model, participants with arsenic exposure and urinary 8-OHdG levels higher than the median had a higher risk of bladder cancer (HR = 4.60, confidence interval: 1.43–14.85). Overall, the combined effects of high cumulative arsenic exposure from artesian well-water and advanced DNA damage predicted the risk of bladder cancer.
•The subjects were followed for two decades in an arseniasis endemic area of northeastern Taiwan.•The urinary 8-OHdG and N7-MeG positively associated with cumulative well arsenic exposure.•Arsenic exposure and 8-OHdG have joint effects on risk of kidney/bladder cancer.
Background
Studies addressing both lymphovascular invasion (LVI) and perineural invasion (PNI) in patients with esophageal squamous cell carcinoma (ESCC) treated with or without neoadjuvant therapy ...are limited. We aimed to analyze the incidence and prognostic significance of LVI and PNI in patients with thoracic ESCC.
Methods
This retrospective study included 520 patients with ESCC: 174 patients after neoadjuvant treatment followed by surgery and 346 after primary esophagectomy, from two medical centers. The relationships between LVI, PNI, and other histological factors were evaluated. The Cox regression model was used for survival analysis.
Results
Positive LVI and PNI were noted in 35.6% and 22.4% of patients with residual primary tumor after neoadjuvant treatment and in 39.6% and 24.0% of patients who underwent primary esophagectomy, respectively. In patients with neoadjuvant treatments, the 5-year overall survival rates were 12.7% and 28.3% in patients with positive LVI and negative LVI, respectively (
p
= 0.001). The 5-year overall survival rates were 6.4% and 29.9% in patients with positive PNI and negative PNI, respectively (
p
< 0.001). In patients who did not receive neoadjuvant treatment, the 5-year overall survival rates were 28.2% and 61.1% in patients with positive LVI and negative LVI, respectively (
p
< 0.001). The 5-year overall survival rates were 30.2% and 52.5% in patients with positive PNI and negative PNI (
p
< 0.001). In subgroup analysis, the presence of PNI was an independent prognostic factor in patients with neoadjuvant treatments, whereas the presence of LVI had more significant prognostic impact in patients with node-negative ESCC after primary esophagectomy.
Conclusions
Both LVI and PNI statuses are significant prognostic factors for patients with ESCC. However, the prognostic impact of LVI was majorly in the subgroup of node-negative patients who received primary esophagectomy.
The endoplasmic reticulum (ER) has diverse functions, and especially misfolded protein modification is in the focus of this review paper. With a highly regulatory mechanism, called unfolded protein ...response (UPR), it protects cells from the accumulation of misfolded proteins. Nevertheless, not only does UPR modify improper proteins, but it also degrades proteins that are unable to recover. Three pathways of UPR, namely PERK, IRE-1, and ATF6, have a significant role in regulating stress-induced physiological responses in cells. The dysregulated UPR may be involved in diseases, such as atherosclerosis, heart diseases, amyotrophic lateral sclerosis (ALS), and cancer. Here, we discuss the relation between UPR and cancer, considering several aspects including survival, dormancy, immunosuppression, angiogenesis, and metastasis of cancer cells. Although several moderate adversities can subject cancer cells to a hostile environment, UPR can ensure their survival. Excessive unfavorable conditions, such as overloading with misfolded proteins and nutrient deprivation, tend to trigger cancer cell death signaling. Regarding dormancy and immunosuppression, cancer cells can survive chemotherapies and acquire drug resistance through dormancy and immunosuppression. Cancer cells can also regulate the downstream of UPR to modulate angiogenesis and promote metastasis. In the end, regulating UPR through different molecular mechanisms may provide promising anticancer treatment options by suppressing cancer proliferation and progression.
Background
Pathologic complete lymph node regression (LNR), where the lymph nodes show evidence of neoadjuvant treatment effect but have no viable residual tumor cells, is sometimes observed ...following neoadjuvant treatments and has been shown to be prognostic; conflicting results exist in the current literature.
Methods
Patients who received neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy for squamous carcinoma (ESCC) were retrospectively reviewed and classified according to their LNR score; 0: N(−) with no evidence of tumor involvement or regression; 1: N(−) with evidence of complete regression; 2: N(+) with < 50% viable tumor; and 3: N(+) with > 50% viable tumor.
Results
In total, 136 patients, comprising 73, 25, 16, and 22 patients with LNR scores of 0, 1, 2, or 3, respectively, were included. Pathologic complete LNR (LNR 1) was significantly associated with lower risks of lymphovascular invasion (0%,
p
< 0.001) and perineural invasion (4%,
p
= 0.038), and a higher rate of pathologic complete response in the primary tumor (76%,
p
< 0.001). The 5-year overall survival rates were 42.1%, 52.8%, and 8.0% in patients with an LNR score of 0, 1, and 2/3, respectively (
p
< 0.001). There was no significant difference between patients with LNR scores of 0 and 1 in overall survival (
p
= 0.454), disease-free survival (
p
= 0.501), and cumulative incidence of recurrences (hazard ratio 0.84, 95% confidence interval 0.432–1.623,
p
= 0.601).
Conclusions
Pathologic complete LNR could be an indicator of nCRT sensitivity and can be regarded as a good prognostic factor in patients with ESCC.
Graphic Abstract
In the survival curve analysis that included patients with lymph node regression (LNR) scores of 0 (blue), 1 (red), and 2/3 (green), we found that patients with pathologic complete LNR (LNR 1), which suggests prior positive nodal involvement, had similar outcomes as those without evidence of prior tumor involvement in lymph node (LNR0).
Novel ZnV2O6 ceramic was synthesized using the solid-state process. A single monoclinic crystalline phase with a space group C2/m was detected at the sintering temperatures ranging from 580 to ...670 °C. The correlations between the chemical bond parameters and microwave dielectric properties were analyzed using the P-V-L bond theory. The full width at half maximum (FWHM) of the most intense Raman peak at 914 cm–1 is inversely proportional to the Q×f value. The ZnV2O6 ceramic can be well-sintered at 640 °C to exhibit an excellent combination of microwave dielectric properties (εr =14.6, Q×f =46,000 GHz and τf =–42 ppm/°C). Additionally, the specimen sintered at 580 °C (εr =13.2, Q×f =28,000 GHz and τf =–5.2 ppm/°C) is also suggested for highly thermal-stable applications. Both samples can be used as ultra-low-temperature co-fired ceramics (ULTCCs) for high-frequency applications.
Over the past decades, promising therapies targeting different signaling pathways have emerged. Among these pathways, apoptosis has been well investigated and targeted to design diverse ...chemotherapies. However, some patients are chemoresistant to these therapies due to compromised apoptotic cell death. Hence, exploring alternative treatments aimed at different mechanisms of cell death seems to be a potential strategy for bypassing impaired apoptotic cell death. Emerging evidence has shown that necroptosis, a caspase-independent form of cell death with features between apoptosis and necrosis, can overcome the predicament of drug resistance. Furthermore, previous studies have also indicated that there is a close correlation between necroptosis and reactive oxygen species (ROS); both necroptosis and ROS play significant roles both under human physiological conditions such as the regulation of inflammation and in cancer biology. Several small molecules used in experiments and clinical practice eliminate cancer cells via the modulation of ROS and necroptosis. The molecular mechanisms of these promising therapies are discussed in detail in this review.
Background
The role of extracapsular lymph node involvement (ELNI) in esophageal cancer has not been fully investigated. We aim to assess its incidence and prognostic significance in patients with ...esophageal squamous cell carcinoma (ESCC) treated with and without neoadjuvant treatments.
Methods
Data of patients who underwent esophagectomy for ESCC in a single medical center was retrospectively reviewed. Patients with positive lymph node involvement were classified as either with ELNI or without ELNI (intracapsular lymph node involvement, ILNI). The impact of ELNI on overall survival (OS), disease-free survival (DFS), and disease recurrence was analyzed.
Results
A total of 336 patients, including 179 without (NCRT −) and 157 with (NCRT +) neoadjuvant chemoradiotherapy, were included. Seventy-two of 179 (40.2%) patients in NCRT − group were with positive lymph node, of whom 19 (26.4%) had ELNI, whereas 49 (31.2%) patients in NCRT + group had positive lymph node, of whom 25 (51.0%) had ELNI. In NCRT + group, patients with ELNI had worse outcome compared to those with ILNI in 5-year OS (10.4 vs. 13.8%,
p
= 0.008), and DFS (5.3 vs. 17.5%,
p
= 0.008). The presence of ELNI was also associated with more distant recurrence (
p
= 0.03). In contrast, there was no survival difference between patients with ELNI and ILNI in NCRT − group.
Conclusions
Compared with ILNI, ELNI is a significant poor prognostic factor in patients with ESCC treated with neoadjuvant treatments, but not in those with primary surgery.
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