ObjectiveTrends in the incidence, disability-adjusted life-years (DALYs), and mortality rate of cervical cancer remain unknown.MethodsThe average annual percent changes (AAPCs) and relative risks (RR) in the incidence, DALYs, and mortality rate were determined using a joinpoint regression analysis; the net age, period, and cohort effects on above rates were evaluated.ResultsA significant increase in age-standardized incidence (AAPC, 0.9%; 95CI: 0.8, 1.1) but significant decreases in age-standardized DALYs (AAPC, -0.4%; 95%CI: -0.60, -0.20) and the mortality rate (AAPC, -0.4%; 95CI: -0.6, –0.3) were observed. As for age-specific rates, the incidence was higher in younger age groups, and the DALYs and mortality rate were lower in older age groups. The effects of age included a slight but significant increase in the RR with advancing age from 35 to 94 years; the period effect included a significant increase in the incidence over the 2005–2019 periods; and the cohort effect included a substantial increase in the incidence from earlier to later birth cohorts.ConclusionsThe incidence of cervical cancer increased from 1990 to 2019, particularly in younger age groups, and the DALYs and mortality rate decreased in the older age groups. Furthermore, the incidence increased with age, period, and cohort.
Background: Colorectal cancer (CRC) remains a leading cause of cancer-related deaths globally. Despite improved understanding of its initiation and progression, and advances in diagnostic or therapeutic strategies, the treatment of metastatic CRC remains a clinical challenge, necessitating identification of novel efficacious therapeutics with little/no toxicity to non-tumor colorectal cells. The present study investigated the effect of Epiblastin A, an adenosine triphosphate (ATP)-mediated competitive inhibitor of casein kinase 1α (CK1α) on the viability, proliferation, and oncogenicity of CRC cells.Methods: Comparative evaluation of the effect of Epiblastin A on CK1α in fetal human normal colonic mucosa (FHC) and CRC (HCT116, HT29, DLD1) cell lines, using western blot, immunohistochemical staining, real-time polymerase chain reaction (RT-PCR), and sulforhodamine B (SRB) cytotoxicity assays.Primary culture cells, patient-derived xenograft (PDX), and tumor xenograft mice CRC models were also employed. Kaplan-Meier plots were used for survival analysis of our CRC cohort.Results: CRC cells aberrantly express CK1α at mRNA and protein levels. This overexpression of CK1α is strongly associated with worse 5-year overall survival (OS) in patients with CRC. Epiblastin A inhibits CK1α and compared to its apparent non-effect on FHC cells regardless of concentration, it elicits significant dosedependent inhibition of the viability of HT29, HCT116, and DLD1 cells with a 48 h IC 50 of 6.8, 5.0, and 3.2 μM, respectively. The expression of CK1α in CRC primary cultures and PDX samples, significantly correlated with Ki-67 expression, and both were attenuated by Epiblastin A. We also observed that the effect of 5 mg/kg Epiblastin A on tumor volume, and body weight in the CRC PDX mice models, was similar to that of 5 mg/kg Cetuximab over the time-course of our in vivo study. In DLD1-derived tumor xenograft mice, Epiblastin A with very mild effect on mice body weight, suppressed tumor volume and tumor weight in a CK1α-dependent manner (P=0.024). Conclusions:Our results demonstrate the efficacy of Epiblastin A in CRC and its potential as a putative small-molecule inhibitor of CK1α and Ki-67 signaling, which are relevant in the CRC initiation, progression and prognosis.
Carcinoma with signet ring cell differentiation is uncommon in patients with invasive breast cancer. Clinical evidence has suggested that the prognosis of this tumor is usually poor if the stage is advanced. The case of a 40-year-old female patient with primary cancer in the right breast accompanied by bilateral neck, axillary, right subclavian and mediastinal lymph node metastases, and left breast metastasis is presented in the current study. The patient developed superior vena cava syndrome and was restricted in lifting the upper right limb when presenting at the Third Affiliated Hospital of Shenzhen University, Shenzhen. The histopathological and immunohistochemical features included ~80% of the tumor cell area having a signet ring cell pattern, exhibiting the phenotype of lobular carcinoma, and ~20% of the tumor cell area exhibiting a ductal carcinoma immunophenotype with neuroendocrine expression The patient received chemotherapy with paclitaxel liposomes and doxorubicin hydrochloride liposomes according to the general guidelines for the treatment of stage IV breast carcinoma. The patient achieved a partial response after 4 cycles of treatment, and then experienced progressive disease in the form of brain metastasis after 6 cycles. Owing to the rarity of carcinoma with signet ring cell differentiation in invasive breast carcinoma, this case report discusses the patient's clinical and histopathological characteristics, and the treatment prognosis.
4687 Given the tremendous need for and potential of umbilical cord blood (UCB) to be utilized as a donor source for hematopoietic stem cell (HSC) transplantation in adults, there is a strong push to overcome the constraints created by the limited volumes and subsequent limited HSC and hematopoietic progenitor cell (HPC) numbers available for HSC transplantation from a single collection. Hematopoietic stem cell homing is believed to be critical for the development of methodologies to improve transplant efficiency and subsequently immune reconstitution during hematopoietic stem cell transplantation in clinical setting. We have previously described the functional defect of partial homing receptor in cord blood stem cell (the higher activity of CD26 and the lower expression of P/E-selectin ligand) in vitro. Respectively, we had confirmed that using of glycosylation engineering and CD26 inhibitor can fix the defect of stem cell homing. However, there is no evidence can prove whether the combination would improve the ability of homing. In present study, to explore the use of glycosylation combined with CD26 inhibitor as a method of improving the transplant efficiency of CB CD34+ hematopoietic stem cells (expressing CD45), we utilized the xenotransplanted nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse model in vivo. 6–8 weeks age of NOD/SCID mice were divided into 5 groups (8 mice per group): blank control group (without stem cells infusion); control group (CD34+ cells infusion alone); glycosylation engineering group; CD26 inhibitor group and combination group (glycosylation engineering combined CD26 inhibitor group). Purified CD34+ stem cells (5×105 per mice) derived from fresh UCB by immunomagnetic beads were injected into lethally irradiated NOD/SCID mice intravenously. To investigate the effect of early engraftment in vivo, we monitored the expression of CD45 in peripheral blood and the overall viability rate weekly until the fourth week by flow cytometry. One week after transplantation, there is no expression of CD45 in peripheral blood in any group, but we observed 2.52±1.41% and 4.8% expression in bone marrow of recipient mice respectively in control and glycosylation engineering groups. All mice in the blank control group were dead and overall viability rate were almost the same for the other four groups (80% in control group,80% in glycosylation engineering group, 100% in CD26 inhibitor group and 100% in combination group). The second week, there is only expression of CD45 in recipient mice for combination group 0.63±0.37%. The overall survival rate among control were significantly lower than the other four groups (40% in control group,80% in glycosylation engineering group, 100% in CD26 inhibitor group and 100% in combination group, P<0.05). In the third week, all groups except the blank control group expressed CD45 in peripheral blood, we observed 0.81±0.12%, 2.81±0.14%, 3.12±0.53% and 7.05±0.87% in peripheral blood of recipient mice for control, glycosylation engineering, CD26 inhibitor treated and combination group. The overall survival rate among CD26 inhibitor treated and combination groups were significantly higher than the other three groups. (40% in control group,40% in glycosylation engineering group, 80% in CD26 inhibitor group and 80% in combination group, P<0.05). In the fourth week, we observed 15.87±0.21%, 30.51±0.62%, 34.33±0.82% and 40.22±1.62% in peripheral blood of recipient mice for control, glycosylation engineering, CD26 inhibitor treated and combination group. The overall survival rate among CD26 inhibitor treated and combination groups were significantly higher than the other three groups. (40% in control group,40% in glycosylation engineering group, 80% in CD26 inhibitor group and 80% in combination group, P<0.05). These results provide the evidence that the combination of two methods have better effect on early implantation than use them respectively. Our results also supported the potential use of CD26 inhibitor combined with glycosylation engineering to treat the umbilical blood which the number of stem cell is less than bone marrow and peripheral blood during hematopoietic stem cell transplantation as a method to improve the transplant efficiency. Furthermore, we aimed to investigate the long-term implantation effect of combination of glycosylation engineering and inhibition of CD26 in vivo. Disclosures: Sun: International Cooperation Research Fund of Anhui Provincial Scientific and Technologic Committee (08080703026): Research Funding; Fund of the Key Medical Project of Anhui Provincial healthy department (2010A005): Research Funding; Anhui Provincial “115” Industrial Innovation Program: Research Funding.
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