Corrigendum to "Cilengitide inhibits osteoclast adhesion through blocking the αvß3-mediated FAK/Src signaling pathway" [Heliyon 9(7) (July 2023) e17841].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e17841.].

Citric acid-modified pH-sensitive bone-targeted delivery of estrogen for the treatment of postmenopausal osteoporosis.

Bone targeted delivery of estrogen offers great promise for the clinical application of estrogen in the treatment of postmenopausal osteoporosis (PMOP). However, the current bone-targeted drug delivery system still has several issues that need to be solved, such as the side effects of bone-targeted modifier molecules and the failure of the delivery system to release rapidly in the bone tissue. It is important to aggressively search for new bone-targeted modifier molecules and bone microenvironment-responsive delivery vehicles. Inspired by the distribution of citric acid (CA) mainly in bone tissue and the acidic bone resorption microenvironment, we constructed a CA-modified diblock copolymer poly(2-ethyl-2-oxazoline)-poly(ε-caprolactone) (CA-PEOz) drug delivery system. In our study, we found that the CA modification significantly increased the bone targeting of this drug delivery system, and the delivery system was able to achieve rapid drug release under bone acidic conditions. The delivery system significantly reduced bone loss in postmenopausal osteoporotic mice with a significant reduction in estrogenic side effects on the uterus. In summary, our study shows that CA can act as an effective bone targeting modifier molecule and provides a new option for bone targeting modifications. Our study also provides a new approach for bone-targeted delivery of estrogen for the treatment of PMOP.

Cilengitide inhibits osteoclast adhesion through blocking the αvß3-mediated FAK/Src signaling pathway.

The remodeling of actin cytoskeleton of osteoclasts on the bone matrix is essential for osteoclastic resorption activity. A specific regulator of the osteoclast cytoskeleton, integrin αvß3, is known to provide a key role in the degradation of mineralized bone matrixes. Cilengitide is a potent inhibitor of integrins and is capable of affecting αvß3 receptors, and has anti-tumor and anti-angiogenic and apoptosis-inducing effects. However, its function on osteoclasts is not fully understood. Here, the cilengitide role on nuclear factor κB ligand-receptor activator (RANKL)-induced osteoclasts was explored. Cells were cultured with varying concentrations of cilengitide (0,0.002,0.2 and 20 µM) for 7 days, followed by detected via Cell Counting Kit-8, staining for tartrate resistant acid phosphatase (TRAP), F-actin ring formation, bone resorption assays, adhesion assays, immunoblotting assays, and real-time fluorescent quantitative PCR. Results demonstrated that cilengitide effectively restrained the functionality and formation of osteoclasts in a concentration-dependent manner, without causing any cytotoxic effects. Mechanistically, cilengitide inhibited osteoclast-relevant genes expression; meanwhile, cilengitide downregulated the expression of key signaling molecules associated with the osteoclast cytoskeleton, including focal adhesion kinase (FAK), integrin αvß3 and c-Src. Therefore, this results have confirmed that cilengitide regulates osteoclast activity by blocking the integrin αvß3 signal pathway resulting in diminished adhesion and bone resorption of osteoclasts.

Colorectal cancer concealment predicts a poor survival: a retrospective study.

OBJECTIVES: Understanding the situation of cancer awareness which doctors give to patients might lead to prognostic prediction in cases of of colorectal cancer (CRC). METHODS: Subsets of 10,779 CRC patients were used to screen the risk factors from the Cancer Registry in Pudong New Area in cancer awareness, age, TNM stage, and gender. Survival of the patients was calculated by the Kaplan-Meier method and assessed by Cox regression analysis. The views of cancer awareness in doctors and patients were surveyed by telephone or household. RESULTS: After a median observation time of 1,616 days (ranging from 0 to 4,083 days) of 10,779 available patients, 2,596 of the 4,561 patients with cancer awareness survived, whereas 2,258 of the 5,469 patients without cancer awareness and 406 of the 749 patients without information on cancer awareness died of the disease. All-cause and cancer- specific survival were poorer for the patients without cancer awareness than those with (P < 0.001 for each, log- rank test). Cox multivariate regression analysis showed that cancer concealment cases had significantly lower cancer-specific survival (hazard ratio (HR) = 1.299; 95 % confidence interval (CI): 1.200-1.407)and all-cause survival (HR = 1.324; 95 % CI: 1.227-1.428). Furthermore, attitudes of cancer awareness between doctors and patients were significantly different (P < 0.001). CONCLUSION: Cancer concealment, not only late-stage tumor and age, is associated with a poor survival of CRC patients.

Cancer incidence and patient survival rates among the residents in the Pudong New Area of Shanghai between 2002 and 2006.

With the growing threat of malignancy to health, it is necessary to analyze cancer incidence and patient survival rates among the residents in Pudong New Area of Shanghai to formulate better cancer prevention strategies. A total of 43,613 cancer patients diagnosed between 2002 and 2006 were recruited from the Pudong New Area Cancer Registry. The incidence, observed survival rate, and relative survival rate of patients grouped by sex, age, geographic area, and TNM stage were calculated using the Kaplan-Meier, life table, and Ederer II methods, respectively. Between 2002 and 2006, cancer incidence in Pudong New Area was 349.99 per 100,000 person-years, and the 10 most frequently diseased sites were the lung, stomach, colon and rectum, liver, breast, esophagus, pancreas, brain and central nervous system, thyroid, and bladder. For patients with cancers of the colon and rectum, breast, thyroid, brain and central nervous system, and bladder, the 5-year relative survival rate was greater than 40%, whereas patients with cancers of the liver and pancreas had a 5-year relative survival rate of less than 10%. The 1-year to 5-year survival rates for patients grouped by sex, age, geographic area, and TNM stage differed significantly (all P < 0.001). Our results indicate that cancer incidence and patient survival in Pudong New Area vary by tumor type, sex, age, geographic area, and TNM stage.

[Incidence and survival condition of primary liver cancer among residents in Pudong district of Shanghai, from 2002 to 2011].

OBJECTIVE: To analyze the incidence and survival rates of primary liver cancer (PLC) among residents in Pudong district of Shanghai. METHODS: Permanent residents of Pudong district, Shanghai were recruited in the study between 2002 and 2011, among whom 7981 PLC cases were diagnosed and 7233 death cases were certified. Both morbidity and mortality of PLC were calculated and standardized (ASR) by the world population of 1966, in order to analyze the survival condition of PLC patients on gender or address, to explore the prognosis of surgical excision treatment. RESULTS: Among the incident cases of PLC between 2002 and 2011, 5754 cases were males, with an average age of 60.27; while 2227 cases were females, with an average age of 68.26. The crude incidence rate for both sexes was 30.73 per 100 000 person-year, and was 44.30 per 100 000 person-year for males, higher than that in females, 17.16 per 100 000 person-year. The difference showed statistical significance (u = 3.46, P < 0.01). The ASR for incidence rates were 25.72 per 100 000 person-year in males and 8.22 per 100 000 person-year in females, respectively, with difference statistically significant (u = 3.00, P < 0.01). There were 7233 PLC death cases in total, including 5151 males and 2082 females, with the crude mortality rate as 27.85 per 100 000 person-year. Rate for males was 39.65 per 100 000 person-year, significantly different from 16.04 per 100 000 person-year in females, statistically (u = 3.16, P < 0.01). The ASRs for mortality were 22.77 per 100 000 person-year in males and 7.39 per 100 000 person-year in females, with statistically significant difference (u = 2.80, P < 0.01). Both incidence and mortality rates increased apparently for males aged over 35 and females aged over 45. The 1- to 5-year survival rates of PLC were 19.88%, 14.91%, 12.19%, 10.29% and 8.56%, respectively. There were statistically significant differences among urban, town and rural areas in the over-all survival rates (χ(2) = 8.711, P = 0.013); The differences in 1- to 5-year survival rates between surgical and non-surgical groups showed statistically significant differences (u = 10.8, 6.93, 4.75, 3.3 and 2.61, respectively, P < 0.01). CONCLUSION: The incidence and mortality rates in males were significantly higher than in females and the over-all survival in rural area was significantly lower than in other areas of Pudong district, suggesting that surgical treatment could improve the prognosis of PLC.