Immunoglobulin‑like transcript (ILT) 4, a negative regulator of immune response in allograft rejection, autoimmunity and infectious diseases, has recently been determined to serve important roles in tumor development. In the present study, the co‑expression of ILT4 and human leukocyte antigen‑G (HLA‑G) in tissues of human primary colorectal cancer (CRC) was revealed, and its association with older age, advanced stage, regional lymph node involvement and poor overall survival time was identified. In CRC cell lines, ILT4 and HLA‑G co‑expression and their autocrine regulation was demonstrated. ILT4 interference affected HLA‑G expression and regulated the cell proliferation, invasion and migration of CRC. HLA‑G fusion protein treatment also increased ILT4 expression in a dose‑dependent manner, thereby activating protein kinase B (AKT) and extracellular signal‑regulated kinase (ERK) signaling, and facilitating the proliferation, migration and invasion of CRC cells. Additionally, the AKT and ERK activation, and CRC cell malignant characteristics induced by HLA‑G may be suppressed by blocking ILT4. The present results indicated that the interaction of ILT4 and its ligand HLA‑G promotes CRC progression through AKT and ERK signal activation, providing a novel strategy of blocking ILT4/HLA‑G for the treatment of CRC.
There is no definitive conclusion so far on the predictive values of ERCC1 polymorphisms for clinical outcomes of platinum-based chemotherapy in non-small cell lung cancer (NSCLC). We updated this meta-analysis with an expectation to obtain some statistical advancement on this issue.Relevant studies were identified by searching MEDLINE, EMBASE databases from inception to April 2015. Primary outcomes included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). All analyses were performed using the Review Manager version 5.3 and the Stata version 12.0.A total of 33 studies including 5373 patients were identified. ERCC1 C118T and C8092A could predict both ORR and OS for platinum-based chemotherapy in Asian NSCLC patients (CT + TT versus CC, ORR: OR = 0.80, 95% CI = 0.67-0.94; OS: HR = 1.24, 95% CI = 1.01-1.53) (CA + AA versus CC, ORR: OR = 0.76, 95% CI = 0.60-0.96; OS: HR = 1.37, 95% CI = 1.06-1.75).Current evidence strongly indicated the prospect of ERCC1 C118T and C8092A as predictive biomarkers for platinum-based chemotherapy in Asian NSCLC patients. However, the results should be interpreted with caution and large prospective studies are still required to further investigate these findings.
Abstract BACKGROUND: For the recent prevention of chemotherapy-induced nausea and vomiting (CINV) in children aged 6 months and older, neurokinin-1(NK-1) receptor antagonists were suggested. However, there is little information available on how to select NK-1 receptor antagonists for pediatric patients, such as aprepitant and fosaprepitant. METHODS: Children between the ages of 2 and 12 who were scheduled to undergo chemotherapy that was either mildly or strongly emetic were randomly randomized to receive fosaprepitant (arm-A) or aprepitant (arm-B). For the children in arm-A, ondansetron and dexamethasone were administered intravenously, followed by a fosaprepitant infusion. The identical medications were administered to children selected for arm-B, with the exception that aprepitant was used instead of fosaprepitant. Dexamethasone and ondansetron were continuously administered for 48 hours following the conclusion of treatment. The proportion of patients who experienced a complete response (CR), which is defined as no vomiting, no retching, and no need for rescue medication, during the acute phase (0-24 hours after the last dose of chemotherapy) was administered, was the study's main end point. The percentage of patients who achieved a CR overall and within the delayed period (24-120 hours) following the last chemotherapy treatment were considered secondary end goals. RESULTS : A total of 108 patients were examined (55 in the fosaprepitant arm and 53 in the aprepitant arm). In the acute phase (95% vs 79%, P =0.018, P<0.05), delayed phase (71% vs 66%, P =0.586), and overall phase (69% vs 57%, P =0.179), CR rates were greater in the fosaprepitant arm than in the aprepitant arm. Additionally, there is no difference between the aprepitant arm (11%) and the fosaprepitant arm (7%) in terms of the desire for rescue anti-emetics. CONCLUSIONS: Adding fosaprepitant to ondansetron and dexamethasone is more beneficial than adding aprepitant for preventing CINV in the acute phase. Fosaprepitant and aprepitant, however, do not significantly differ from one another for prevention throughout the delayed and overall phases. This study was approved by IRB of Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine (No. SCMCIRB-K2020120-2), and it was prospectively registered with the ClinicalTrials.gov on April 22, 2021 (reference number: NCT04873284 ).
Extrachromosomal circular DNA (eccDNA), a novel class of DNA with a circular topological structure, is present in a variety of cancer cells and tissues and may play broad roles in processes ranging from aging to cancer cell heterogeneity through multiple mechanisms. EccDNA has been characterized by profile, structure and function in several prominent studies but its effect on hydroquinone (HQ)-induced malignantly transformed cells (TK6-HQ) is still elusive.
Abstract Background Understanding the annual incidence, mortality, and disability-adjusted life-years (DALYs) for mesothelioma globally provides essential foundations for cancer control, policy decisions and resource allocation. Materials and methods Complying with the Global Burden of Disease Study 2019, we extracted the data of incidences, deaths and DALYs in 204 countries and territories from 1990 to 2019. Average annual percentage changes were used to quantify the temporal trends in mesothelioma burden. Besides, the population attributable fractions of the risk factor of mesothelioma were also estimated. Results Globally, 34511 (95% uncertainty intervals[UI]: 31199, 37771) incident cases, 29251 (95%UI: 26668, 31006) deaths and 668104 (95%UI: 608269, 716475) DALYs of mesothelioma were estimated in 2019. The age-standardized rates of incidence, mortality and DALYs all showed a slightly declining trend over the past 30 years, but the latest absolute number of mesothelioma burden almost doubled since 1990. The age-standardized burden of mesothelioma among men was around 3 times more than women in 2019, which decreased among women while remained stable among men. The burden rate decreased among the population aged under 70 years, but increased among the population aged over 80 years, especially in the High socio-demographic index (SDI) region. The age-standardized DALYs rate (ASDR) of mesothelioma attributable to occupational asbestos exposure in 2019 was positively associated with SDI at the national levels (ρ = 0.3105, P = 6.2e-06). Conclusion This study depicted a continuous increase in incidences, deaths and DALYs of mesothelioma globally over the past 30 years. Controlling occupational asbestos exposure will reduce the mesothelioma burden, especially for higher SDI regions.
Hydroquinone (HQ) is one of the major metabolites of benzene and can cause abnormal gene expression. It is a known carcinogen that alters cell cycle disruption and cell proliferation. However, its chemical mechanism remain a mystery. Circular RNAs (circRNAs) are a subtype of noncoding RNAs (ncRNAs) that play a variety of roles in biological processes. Hsa_circ_001944 expression was upregulated in 30 leukemia patients and HQ-induced malignant transformed TK6 cells. Hsa_circ_001944 silencing inhibited the growth of HQ-TK6 cells and halted the cell cycle. The silencing of hsa_circ_0001944 led to increased cell accumulation in G1 versus S phase, increased apoptosis in the sh1944 versus the shNC group, and increased levels of DNA damage (γ-H2AX), leading to cell cycle arrest. In summary, inhibition of hsa_circ_001944 restricted cell growth by inhibiting cell cycle arrest and induced growth of HQ-TK6 cells by modulating PARP1 expression. Hsa_circ_0001944 targeted HuR, which is a kind of RNA-binding protein, to control PARP1 expression via RNAinter, RBPmap, and RBPdb. Fluorescence in situ hybridization combined with immunofluorescent labeling and western blotting experiments showed that hsa_circ_001944 was able to dissociate HuR and PARP1 binding in HQ-TK6 cells, control PARP1 production, and ultimately alter the PARP1/H-Ras pathway.
Abstract Background Toxoplasma gondii , an obligate intracellular apicomplexan parasite, infects a wide range of warm-blooded animals including humans. T. gondii expresses five members of the C1 family of cysteine proteases, including cathepsin B-like (TgCPB) and cathepsin L-like (TgCPL) proteins. TgCPB is involved in ROP protein maturation and parasite invasion, whereas TgCPL contributes to proteolytic maturation of proTgM2AP and proTgMIC3. TgCPL is also associated with the residual body in the parasitophorous vacuole after cell division has occurred. Both of these proteases are potential therapeutic targets in T. gondii . The aim of this study was to investigate TgCPB and TgCPL for their potential as DNA vaccines against T. gondii. Methods Using bioinformatics approaches, we analyzed TgCPB and TgCPL proteins and identified several linear-B cell epitopes and potential Th-cell epitopes in them. Based on these results, we assembled two single-gene constructs (TgCPB and TgCPL) and a multi-gene construct (pTgCPB/TgCPL) with which to immunize BALB/c mice and test their effectiveness as DNA vaccines. Results TgCPB and TgCPL vaccines elicited strong humoral and cellular immune responses in mice, both of which were Th-1 cell mediated. In addition, all of the vaccines protected the mice against infection with virulent T. gondii RH tachyzoites, with the multi-gene vaccine (pTgCPB/TgCPL) providing the highest level of protection. Conclusions T. gondii CPB and CPL proteases are strong candidates for development as novel DNA vaccines.
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