[Effect of growth hormone supplementation on liver and lung function in patients with hypopituitarism].

To analyze the clinical features of patients with anterior hypopituitarism (HP) complicated with cirrhosis, and to explore the effects of growth hormone supplementation on liver and lung function. A total of 11 patients with HP complicated with cirrhosis admitted to Peking Union Medical College Hospital from January 2016 to December 2022 were included in the study, including 8 males and 3 females, aged [M(Q1, Q3)]31 (20, 37) years. There were 6 patients with pituitary stalk interruption syndrome, 4 patients after craniopharyngioma resection, and 1 patient after germinal cell tumor chemoradiotherapy. Cirrhosis appeared at [M(Q1, Q3)]7 (1, 16) years after the diagnosis of HP. There were 7 cases complicated with hepatopulmonary syndrome (HPS). The liver and lung function of 5 patients were improved significantly after the addition of growth hormone, and the arterial partial pressure of oxygen increased from (47±11) mmHg(1 mmHg=0.133 kPa) to (84±12) mmHg. Timely supplementation of growth hormone can improve the symptoms of fatty liver, cirrhosis and HPS, and postpone or even avoid the transplantation of liver and other organs.

The incidences of adverse events in small-cell lung cancer patients after radiotherapy and immunotherapy treatment: a systematic review and meta-analysis.

Immunotherapy is important in treating small-cell lung cancer (SCLC), and its anti-tumor effects are better when combined with radiotherapy. However, the toxicity of this combination is little known. This study assessed the incidences of adverse events when adding radiotherapy to ICIs in patients with SCLC. We searched the online databases to identify eligible studies and included nine references. For extensive-stage SCLC patients, the median PFS ranged from 4.5 to 12.5 months, and median OS ranged from 8.4 to NR months, respectively. The incidences of grade 3 or higher pneumonitis, lung infection, diarrhea, and fatal adverse events were 8.7% (95% CI: 5%-14.7%), 6.7% (95% CI: 2.5%-16.5%), 12.6% (95% CI: 7.6%-20%), and 5.1% (95% CI: 2.1%-11.6%), respectively. Our findings suggest that radiotherapy plus ICIs may provide acceptable safety and favorable efficacy for SCLC patients.

[Cardiometabolic disease patterns among elderly patients with colorectal cancer in China].

Objective: To explore the distribution patterns of cardiometabolic diseases (CMD) in elderly patients with colorectal cancer, and provide a reference for the prevention and treatment of cardiovascular metabolic diseases in these patients. Methods: Clinical data of 3 894 elderly patients with colorectal cancer from January 2008 to March 2018 admitted in the Chinese PLA General Hospital were recruited and the incidence rate of CMD was retrospectively analyzed. The influence factors of elderly patients with colorectal cancer combined with CMD were analyzed by multivariate Logistic regression model. Results: The morbidity rate of CMD in elderly patients with colorectal cancer is 33.4% (1 301/3 894), among them, the morbidity rate of the male was 31.9% (768/2 409), and that of the female was 35.9% (533/1 485). There was not significant difference between these two sex (P=0.074). The morbidity rates of CMD in patients of 65-74 years, 75-84 years and ≥85 years were 30.6% (754/2 462), 37.0% (479/1 294) and 49.3% (68/138), respectively, with significant differences (P<0.001). Multiple Logistic regression analysis revealed that female (OR=1.213, 95%CI: 1.056-1.394), age (75-84 years group: OR=1.344, 95%CI: 1.164-1.552; ≥85 years group: OR=2.345, 95%CI: 1.651-3.331) and body mass index (BMI 18.5-24.9 kg/m(2) group: OR=1.319, 95%CI: 1.065-1.638; ≥25 kg/m(2) group: OR=2.041, 95%CI: 1.627-2.561) were independent risk factors for elderly colorectal cancer patients with CMD. Conclusion: The morbidity rate of CMD in elderly patients with colorectal cancer increases with age and it is urgent to strengthen multidisciplinary cooperation and develop reasonable treatment plans to extend the survival and life quality of these patients.

[Effects and mechanisms of allogeneic epidermal stem cells on the survival of allogeneic full-thickness skin grafts in nude mice with full-thickness skin defect wounds].

Objective: To investigate the effects and mechanisms of allogeneic epidermal stem cells (ESCs) on the survival of allogeneic full-thickness skin grafts in nude mice with full-thickness skin defect wounds. Methods: Experimental research methods were applied. Primary ESCs that appeared paving stone-like after being cultured for 7 d were obtained by enzymatic digestion method from one 4-week-old male BALB/c-NU nude mouse (the same strain, age, and sex below). The cells of third passage were identified by flow cytometry to positively express ESC marker CD44 and negatively express CD45, meanwhile, the positive expression of ESC markers of p63 and integrin 6α, and negative expression of CD71 were identified by immunofluorescence method. The ESCs of third passage in the logarithmic growth phase were used for the following experiments. Twenty-six nude mice were equally divided into phosphate buffered saline (PBS) group and ESCs group according to the random number table. A full-thickness skin defect wound was made on the back of each nude mouse, and then the wounds of the two groups were sprayed with equal volumes of PBS and ESCs, respectively. The wounds were transplanted with full-thickness skin grafts cut from the backs of 4 other nude mice. Each ten nude mice from the two groups were selected, the wound healing and skin survival on post surgery day (PSD) 0 (immediately), 3, 7, 14, and 21 were observed, and the survival ratio and shrinkage rate of skin grafts on PSD 3, 7, 14, and 21 were calculated (the number of sample was the number of surviving skin grafts at each time point); the blood perfusion in the skin grafts on PSD 3, 7, and 14 was detected by the laser speckle blood flow imager, and the blood flow ratio of nude mice skin grafts in ESCs group to PBS group at each time point was calculated (the number of sample was the pair number of surviving skin grafts in group pairing at each time point). The skin graft tissue of each 3 nude mice remained in the two groups were collected on PSD 7, and the mRNA expressions and protein expressions of tumor necrosis factor α (TNF-α), interleukin 8 (IL-8), IL-10, type Ⅰ collagen, type Ⅲ collagen, and matrix metalloproteinase 9 (MMP-9) in the tissue were detected by real-time fluorescent quantitative reverse transcription polymerase chain reaction and Western blotting, respectively. Data were statistically analyzed with Log-rank test, analysis of variance for repeated measurement, one-way analysis of variance, independent sample t test, and Bonferroni correction. Results: Taking the condition on PSD 0 as a reference, the wounds of nude mice in the two groups healed gradually on PSD 3, 7, 14, and 21, and the shrinkage of skin grafts was gradually obvious. Among them, the shrinkage healing of wound of nude mice in PBS group was more significant than that in ESCs group. On PSD 3, the skin graft of 1 nude mouse failed in ESCs group, while the skin graft of 3 nude mice failed in PBS group. On PSD 7, the skin graft of another nude mouse failed in PBS group. The survival ratio of skin grafts of nude mice in the two groups was similar on PSD 3, 7, 14, and 21 (P>0.05). On PSD 3, 7, 14, and 21, the shrinkage rates of skin grafts of nude mice in ESCs group were (9.2±0.4)%, (19.7±1.2)%, (53.6±3.5)%, and (62.2±5.1)%, respectively, which was significantly lower than (11.0±0.9)%, (47.8±2.8)%, (86.1±7.1)%, and (89.7±9.0)% in PBS group (t=5.719, 26.650, 11.940, 7.617, P<0.01). On PSD 3, 7, and 14, blood perfusion signals were observed in the skin grafts of nude mice in the two groups. The average blood perfusion ratios of the skin grafts of nude mice in ESCs group to PBS group were greater than 1, and there was no statistically significant difference in the overall comparison of 3 time points (P>0.05). On PSD 7, compared with those of PBS group, the mRNA and protein expressions of TNF-α, IL-8, type Ⅰ collagen, and type Ⅲ collagen in the skin graft tissue of nude mice in ESCs group were significantly reduced, while the mRNA and protein expressions of IL-10 and MMP-9 in the skin graft tissue of nude mice in ESCs group were significantly increased (in mRNA comparison, t=2.823, 2.934, 2.845, 2.860, 3.877, 2.916, P<0.05). Conclusions: Allogeneic ESCs can reduce the shrinkage of allogeneic full-thickness skin grafts transplanted on full-thickness skin defect wounds in nude mice, promote the formation of new blood vessels between the skin graft and the wound, reduce inflammation and collagen protein expression, and promote the expression of MMP-9, thus improving the survival quality of skin grafts.

Molecular mechanisms of MCM3AP-AS1 targeted the regulation of miR-708-5p on cell proliferation and apoptosis in gastric cancer cells.

The article "Molecular mechanisms of MCM3AP-AS1 targeted the regulation of miR-708-5p on cell proliferation and apoptosis in gastric cancer cells, by H. Wang, T. Xu, L. Wu, H.-L. Xu, R.-M. Liu, published in Eur Rev Med Pharmacol Sci 2020; 24 (5): 2452-2461-DOI: 10.26355/eurrev_202003_20512-PMID: 32196596" has been withdrawn from the authors due to the discovery of new results. The authors decided to improve them further. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20512.

[Evaluation of therapeutic efficacy of arthroplasty with Swanson prosthesis in the surgical treatment of 2-5 metatarsophalangeal joint diseases].

OBJECTIVE: Metatarsophalangeal joint is an important joint for daily weight-bearing walking. Osteoarthritis, osteochondrosis of the metatarsal head, rheumatoid arthritis can often cause the destruction of 2-5 metatarsophalangeal joint, leading to pain, limited joint movement and toe deformities, severely affecting the forefoot function. The purpose of this study is to report the results of middle-long term follow-up after performing Swanson double-stem silicon implant arthroplasty in patients with diseases of 2-5 metatarsophalangeal joint. METHODS: From January 2010 to October 2015, 21 patients with 2-5 metatarsophalangeal joint replacement were performed with Swanson double-stem silicone prosthesis. In the study, 16 cases were successfully followed up, 2 men and 14 women with an average age (66.7±5.5) years. There were 9 cases diagnosed with rheumatoid arthritis, 5 cases with severe osteoarthritis and 2 cases with osteochondrosis of the metatarsal head. The American Association of foot and ankle surgery Maryland foot scoring system and visual analogue score (VAS) were used to evaluate the walking function, metatarsophalangeal joint mobility and pain degree before and after surgery. RESULTS: The follow-up time ranged from 17 months to 5 years, with an average of 3.2 years. According to Maryland foot scoring system of the American Association of foot and ankle surgery, the preoperative score was (60.69±6.12) points and postoperative score was (88.13±5.84) points. Range of motion of metatarsophalangeal joint: preoperative: back extension 5.4°±3.1°, plantar flexion 4.4°±2.7°; postoperative: back extension 15.7°±4.5°, plantar flexion 12.2°±4.3°, the motion of 2-5 metatarsophalangeal joint after operation was significantly improved compared with that before operation (P < 0.01). The preoperative VAS was (6.8±0.9) points and the last follow-up was (2.3±0.8) points, the pain symptom of metatarsophalangeal joint was improved obviously after operation. The postoperative score was significantly higher than the preoperative score according to Maryland foot scoring system (P < 0.01), the excellent rate was 81.3%. CONCLUSIONS: With the advantages of alleviating pain, preserving the length and alignment of metatarsophalangeal joint, improving the function of walking, and correcting the deformity, Swanson double-stem silicon implant arthroplasty is a reproducible and safe option for the reconstruction of the 2-5 metatarsophalangeal joint. However, there is still some probability of adverse reactions and still room for improvement.

Clinical significance of lncRNA MIR31HG in melanoma.

OBJECTIVE: The aim of this study was to explore the expression of long non-coding RNA (lncRNA) MIR31HG in malignant melanoma (MM), and to investigate its clinical significance. PATIENTS AND METHODS: The quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression of lncRNA MIR31HG in MM tissues and cells. The relationship between lncRNA MIR31HG expression and the clinicopathological characteristics was analyzed. Furthermore, the cell counting kit-8 (CCK-8) and the transwell assays were performed to assess the effect of MIR31HG on cell proliferation and metastasis in vitro, respectively. RESULTS: The expression of MIR31HG was significantly upregulated in MM tissues and cells. To explore the relationship between MIR31HG expression and clinical features, the patients were divided into two groups according to the mean expression of MIR31HG, including high expression group and low expression group. The subsequent results indicated that MIR31HG expression was correlated with lymph nodes metastasis, distal metastasis, and TNM stage. The multivariate analysis indicated that a high expression of MIR31HG could be used as an independent prognostic factor for MM. MIR31HG low-expression cells were constructed in vitro. Compared with the control cells, the cells with low expression of MIR31HG showed significantly low malignancy, including decreased cell proliferation rate and migration and invasion rates. CONCLUSIONS: LncRNA MIR31HG was a novel factor involved in MM progression, which could be used as a potential biomarker and therapeutic target for MM.

Molecular mechanisms of MCM3AP-AS1 targeted the regulation of miR-708-5p on cell proliferation and apoptosis in gastric cancer cells.

OBJECTIVE: Gastric cancer (GC) is a common malignancy of the digestive tract. Accumulated studies proved that long non-coding RNA MCM3AP-AS1 (MCM3AP-AS1) modified the mechanism of the progression of GC. However, the molecular mechanism is still greater elusive. Hence, we aimed to explore the molecular mechanism of MCM3AP-AS1 targeting the regulation of microRNA-708-5p on cell proliferation and apoptosis in GC cells. MATERIALS AND METHODS: The expression levels of MCM3AP-AS1 (MCM3AP antisense RNA 1) in gastric mucosal cells GES-1 and gastric cancer cell lines of MGc-803 and SGC-7901 cells were detected by qRT-PCR. Moreover, the protein levels of Cyclin D1, P21, Bax and Bcl-2 in MGc-803 and SGC-7901 cells after transfection were detected by Western blot. MTT assay was performed to detect cell proliferation and flow cytometry was carried out to determine GC cell apoptosis in vitro. In the endpoint, the targeting relationship between MCM3AP-AS1 and microRNA-708-5p was detected by Dual-Luciferase reporter assay. RESULTS: The level of MCM3AP-AS1 was significantly promoted in GC cell lines. Knockdown of MCM3AP-AS1 curbed cell proliferation and enhanced apoptosis in MGc-803 and SGC-7901 cells. Furthermore, the effect of the downregulation of MCM3AP-AS1 on cell proliferation and apoptosis was reversed by knockdown of miR-708-5p, which was targeted by MCM3AP-AS1 in vitro. CONCLUSIONS: MCM3AP-AS1 regulates the proliferation and apoptosis of gastric cancer cells by targeting the expression of microRNA-708-5p. The study may be useful to the therapy target of human GC.

[Association of health literacy and smoking behaviors among middle school students in six cities of China].

Objective: To explore the association between the health literacy (HL) and smoking behaviors in middle school students. Methods: From November 2015 to January 2016, middle school students in Shenyang City of Liaoning Province, Bengbu City of Anhui Province, Xinxiang City of Henan Province, Ulanqab City of Inner Mongolia Autonomous Region, Chongqing City and Yangjiang City of Guangdong Province were enrolled by using a multistage stratified cluster sampling method. A total of 23 137 questionnaires were issued and 22 628 questionnaires were valid. A questionnaire survey was conducted to collect demographic information, HL and smoking behaviors. The low, middle, and high-level group were classified according to the tertile of HL score. A multiple logistic regression model was conducted to explore the association between the HL and smoking behaviors. Results: The age of subjects was (15.4±1.8) years old, and HL score was (104.1±18.7) points. The proportion of former smoking, recent smoking and passive smoking was 9.2% (2 071), 2.8% (635) and 27.9% (6 304), respectively. The proportion of former smokers who tried to quit smoking was 50.1% (1 037/2 071). Compared to the high-level HL, the low-level HL increased the risk of former smoking [OR (95%CI): 1.85 (1.61-2.13)], recent smoking [OR (95%CI): 1.68 (1.33-2.14)] and passive smoking [OR (95%CI): 1.34 (1.23-1.46)], and decreased the likelihood of smoking cessation [OR (95%CI): 0.70 (0.53-0.92)], after adjusting for the gender, school type, registered residence, household structure, accommodation type, educational level of patients, and self-reported family economic status. Conclusion: The HL of middle school students was related to their smoking behaviors.

[Analysis of CT perfusion imaging in chronic cerebral circulatory insufficiency and its relationship with crossed cerebellar diaschisis].

Objective: To investigate the change of cerebral microcirculation of chronic cerebral circulation insufficiency(CCCI) patients and the relationship between CCCI and crossed cerebellar diaschisis(CCD)by using 320-detector row of low-dose volume CT perfusion imaging. Methods: A total of 158 patients (103 males, 55 females, from 45 to 82 years old, the mean age was 62.9) with symptoms of CCCI were admitted to the First Affiliated Hospital of Wenzhou Medical University from June 2013 to January 2016. Low-dose CTP imaging of whole brain was performed to them using 320-detector row volume CT scanner. The perfusion parameters such as cerebral blood flow(CBF), cerebral blood volume(CBV), mean transit time(MTT), time to peak(TTP) and DLY in both cerebral blood supply areas and cerebellum were got, so were the 4-dimensional CTA images, and rCBF, rCBV, rMTT and rTTP were calculated by ipsilateral/contralateral value. Comparative t-test and independent t-test were applied to analyzing these parameters quantitatively.Chi-square test and Logistic regression model were applied to analyzing the related clinical risk factors. Results: (1) All 108 patients in CCCI group showed asymmetric perfusion within two cerebral hemispheres in CTP images. The CBF, CBV of diseased side were lower than the contralateral mirror area (t(CBF)=-12.89, t(CBV)=-7.031, P(CBF, CBV)<0.001); the MTT of the diseased side was shorter than the contralateral mirror area (t(MTT) =13.310, P(MTT)<0.001); the TTP of the diseased side was longer than the contralateral mirror area (t(TTP)=-4.012, P(TTP)<0.001). The rCBF and rCBV of CCCI group were lower than that in non-CCCI group (t(rCBF)=3.079, t(rCBV)=2.760, P(rCBF, rCBV)<0.01), while the rTTP of CCCI group was longer than that in non-CCCI group (t(rTTP)=4.846, P(rTTP)<0.001). (2)The results of Chi-square test showed that the differences of gender (χ(2)=4.036, P=0.045), hyperlipidemia (χ(2)=7.687, P=0.006), as well as smoking (χ(2)=11.868, P=0.001) had statistical significance between CCCI group and non-CCCI group.Multi-factor Logistic regression analysis showed that hyperlipidemia (OR value=3.736, P=0.016) and smoking (OR value=4.641, P=0.01) were the risk factors of CCCI, while gender had no relationship with it.(3)The incidence of CCD was 18.5% in the CCCI group, and at the same time, the supratentorial corresponding blood supply areas were classified.A total of 10(34.5%) cases were in blood supply area of posterior cerebral artery, 6(20.7%) cases were in blood supply area of middle cerebral artery, 12(41.4%) cases were of anterior cerebral artery, while only 1(3.5%) case was of basal ganglia, in which 4 cases were in blood supply area of posterior cerebral artery, another 4 cases were middle cerebral artery, 7 cases were of anterior cerebral artery and no case of basal ganglia respectively leading CCD alone. Conclusions: CTP could display the microcirculation situation of abnormal brain tissue perfusion area intuitively and quantitatively. Additionally, it could reflect the degree of relationship between cerebral several blood supply areas and cerebellum.

[The clinical features of patients with allergic rhinitis of Nantong city in China].

Objective:To comprehensively analyze the clinical features of patients with AR by a retrospective study. Method:A total number of 8 102 patients diagnosed with AR were enrolled in Nantong area, and detailed clinical data were documented in all cases. Skin prick tests with standardized aeroallergens were conducted in these patients; The samples were divided into two groups(children and adults group) and the clinical features between two groups were analysed. Result:Children in schoolage were the majority of AR patients in children group. There were 4 581 cases(56.54%) with ocular symptoms, 3 977 cases(49.09%)with lower respiratory tract symptoms. Nasal congestion (97.37%) was the most common symptoms in patients with AR,while eye itching(32.68%) was the most common ocular symptoms in patients with AR, followed by the dacryorrhea(23.57%);and cough(44.72%) was the most common lower respiratory tract symptoms. Dermatophagoides pteronyssinus and dermatophagoides farinae had the highest positivity among all allergens, and the shrimp was the main food allergen. Conclusion:We analyzed the clinical features of patients with AR, that would provide a more scientific basis for prevention,clinical diagnosis, treatment and epidemiological studies for AR.

Prognostic significance of Livin expression in nasopharyngeal carcinoma after radiotherapy.

PURPOSE: This study was designed to investigate the expression levels of the inhibitor of apoptosis protein Livin in nasopharyngeal cancer tissues and its prognostic significance in nasopharyngeal carcinoma after radiotherapy. MATERIAL AND METHODS: A total of 83 patients with nasopharyngeal carcinoma who received radiotherapy were enrolled in this study from January 2008 to October 2010. Livin expression in nasopharynx pathological specimens extracted from patients was detected by immunohistochemistry. A Kaplan-Meier analysis was conducted to explore the effects of clinicopathological features and Livin expression on the overall survival and progression-free survival of patients with nasopharyngeal carcinoma, and explore its prognosis relevance after radiotherapy. RESULTS: Of the 83 patients with nasopharyngeal carcinoma, the overall Livin positive expression rate was 65.1% (54 patients), and the overall response rate of radiotherapy was 81.9% (68 patients). Significant differences in radiotherapy efficacy were found between patients who did not express Livin and those who did (P<0.05). The Kaplan-Meier analysis showed that Livin expression, high clinical staging, cervical lymph node metastasis, high T-staging and high N-staging were significantly correlated with a decrease in the overall survival of patients with nasopharyngeal carcinoma (all P<0.05). A Cox multivariate survival analysis showed that Livin expression, clinical staging and N-staging were independent risk factors for the overall survival of patients with nasopharyngeal carcinoma treated with radiation (all P<0.05). Furthermore, Livin expression and clinical staging were independent risk factors for the progression-free survival of patients with nasopharyngeal carcinoma once radiotherapy was introduced (all P<0.05). CONCLUSION: Expression of Livin, an inhibitor of apoptosis proteins, may be closely linked with poor prognosis of nasopharyngeal carcinoma post-radiotherapy and hence it may be a new therapeutic target in the treatment of the disease.

Identification of novel caspase/autophagy-related gene switch to cell fate decisions in breast cancers.

OBJECTIVES: Caspases, a family of cysteine proteases with unique substrate specificities, contribute to apoptosis, whereas autophagy-related genes (ATGs) regulate cytoprotective autophagy or autophagic cell death in cancer. Accumulating evidence has recently revealed underlying mechanisms of apoptosis and autophagy; however, their intricate relationships still remain to be clarified. Identification of caspase/ATG switches between apoptosis and autophagy may address this problem. MATERIALS AND METHODS: Identification of caspase/ATG switches was carried out using a series of elegant systems biology & bioinformatics approaches, such as network construction, hub protein identification, microarray analyses, targeted microRNA prediction and molecular docking. RESULTS: We computationally constructed the global human network from several online databases and further modified it into the basic caspase/ATG network. On the basis of apoptotic or autophagic gene differential expressions, we identified three molecular switches [including androgen receptor, serine/threonine-protein kinase PAK-1 (PAK-1) and mitogen-activated protein kinase-3 (MAPK-3)] between certain caspases and ATGs in human breast carcinoma MCF-7 cells. Subsequently, we identified microRNAs (miRNAs) able to target androgen receptor, PAK-1 and MAPK-3, respectively. Ultimately, we screened a range of small molecule compounds from DrugBank, able to target the three above-mentioned molecular switches in breast cancer cells. CONCLUSIONS: We have systematically identified novel caspase/ATG switches involved in miRNA regulation, and predicted targeted anti-cancer drugs. These findings may uncover intricate relationships between apoptosis and autophagy and thus provide further new clues towards possible cancer drug discovery.

Identification of microRNA-regulated autophagic pathways in plant lectin-induced cancer cell death.

OBJECTIVES: Plant lectins, carbohydrate-binding proteins of non-immune origin, have recently been reported to induce programmed cell death (including apoptosis and autophagy) in many types of cancer cells. MicroRNAs (miRNAs), small, non-coding endogenous RNAs, ~22 nucleotides (nt) in length, have been well characterized to play essential roles in regulation of the autophagy process in cancer; however, how these miRNAs regulate autophagic pathways in plant lectin-induced cancer cells, still remains an enigma. MATERIALS AND METHODS: Identification of microRNA-regulated autophagic pathways was carried out using a series of elegant systems - biology and bioinformatics approaches, such as network construction, hub protein identification, targeted microRNA prediction, microarray analyses and molecular docking. RESULTS: We computationally constructed the human autophagic protein-protein interaction (PPI) network, and further modified this network into a plant lectin-induced network. Subsequently, we identified 9 autophagic hub proteins and 13 relevant oncogenic and tumour suppressive miRNAs, that could regulate these aforementioned targeted autophagic hub proteins, in human breast carcinoma MCF-7 cells. In addition, we confirmed that plant lectins could block the sugar-containing receptor EGFR-mediated survival pathways, involved in autophagic hub proteins and relevant miRNAs, thereby ultimately culminating in autophagic cell death. CONCLUSIONS: These results demonstrate that network-based identification of microRNAs modulate autophagic pathways in plant lectin-treated cancer cells, which may shed new light on the discovery of plant lectins as potent autophagic inducers, for cancer drug discovery.

Targeting apoptosis pathways in cancer with magnolol and honokiol, bioactive constituents of the bark of Magnolia officinalis.

Magnolol and honokiol, main active compounds from the bark of Magnolia officinalis, have been found to have various pharmacological actions, including anti-oxidative, anti-inflammatory, anti-tumor, and anti-microbial properties, without appreciable toxicity. Recently, the anti-tumor activity of magnolol and honokiol has been extensively investigated. Magnolol and honokiol were found to possess anti-tumor activity by targeting the apoptosis pathways, which have been considered as targets for cancer therapies. This review will focus on the mechanisms by which magnolol and honokiol act on apoptosis pathways in cancer that have been characterized thus far, including the death receptor mediated pathway, mitochondria-mediated pathway, caspase-mediated common pathway, and regulation of apoptosis-related proteins. These breakthrough findings may have important implications for targeted cancer therapy and modern applications of traditional Chinese medicine.

Expression of KL-6 mucin, a human MUC1 mucin, in intrahepatic cholangiocarcinoma and its potential involvement in tumor cell adhesion and invasion.

AIMS: Aberrant expressions of KL-6 mucin were proved to be associated with worse tumor behaviors of many carcinomas. This study was to evaluate the expression KL-6 mucin, a human MUC1 mucin, in intrahepatic cholangiocarcinoma (CC) and its significance in tumor progression. MAIN METHODS: KL-6 mucin expressions in 21 patients with CC, 12 with combined hepatocellular and cholangiocarcinoma (cHCC-CC), and 78 with hepatocellular carcinoma (HCC) were detected by immunohistochemical staining. The effects of two glycosylation inhibitors (tunicamycin and benzyl-alpha-N-acetylgalactosamine (BAG)) on CC cell proliferations were assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assays. KL-6 mucin expressions were detected by immunocytochemical staining and western blotting after tunicamycin or BAG treatment. Cell adhesive and invasive properties were evaluated by adhesion tests and transwell chamber assays after tunicamycin or BAG treatment. KEY FINDINGS: Positive KL-6 mucin staining was observed in all CC tissues and CC areas of cHCC-CC tissues. Immunocytochemical staining and western blotting showed that KL-6 mucin expressions were significantly reduced after both inhibitors treatment. Cell adhesive properties were significantly decreased after both inhibitors treatment, while cell invasive abilities were significantly decreased after BAG but not tunicamycin treatment. SIGNIFICANCE: This study indicated that KL-6 mucin might be a specific tumor target for CC. Therapeutic strategies that target glycosylation of KL-6 mucin may be useful to control aggressive behaviors of CC.

Localization of N-myc downstream-regulated gene 1 in gastric cancer tissue.

BACKGROUND AND AIM: N-myc downstream-regulated gene 1 is detected in normal tissue but is down-regulated in cancer tissue. Furthermore, research has suggested that co-expression with p53 is necessary for induction of p53-mediated apoptosis. This study sought to investigate the clinicopathological significance of N-myc downstream-regulated gene 1 and p53 expression in gastric cancer tissue. PATIENTS AND METHODS: Immunohistochemical detection of N-myc downstream-regulated gene 1 and p53 was performed with tissue samples from 96 cases of gastric cancer, and the relationship between expression profiles of proteins and clinicopathological characteristics was statistically analysed. RESULTS: Positive staining of N-myc downstream-regulated gene 1 was observed in the cytoplasm (22 of 96 cases, 22.9%) and/or nucleus (29 of 96 cases, 30.2%) of cancer cells. In 15 cases (15.6%), both cytoplasm-positive cells and nucleus-positive cells were observed in the cancerous region. The nuclear localization of N-myc downstream-regulated gene 1 was frequently observed in the region of cancerous invasion and was significantly related to lymph node metastasis. In addition, accumulation of p53 protein in the nucleus of cancer cells significantly coincided with the nuclear localization of N-myc downstream-regulated gene 1. CONCLUSIONS: Localization of N-myc downstream-regulated gene 1 and its significant correlation with p53 expression may play an important role in cancer progression.

Effect of benzyl-N-acetyl-α-galactosaminide on KL-6 mucin expression and invasive properties of a human pancreatic carcinoma cell line.

KL-6 mucin is a type of MUC1 mucin and its aberrant expression has been shown to be associated with aggressive metastasis and poor clinical outcome in tumors. The present study is to investigate the effects of benzyl-N-acetyl-α-galactosaminide (GalNAc-O-bn), an O-glycosylation inhibitor, on KL-6 mucin expression and invasive properties of a human pancreatic carcinoma cell line, Suit-2 cells. Expression profiles of KL-6 mucin in the cells pretreated with or without 5 mM GalNAc-O-bn for 48 h were examined by Western blotting and immunocytochemical staining and invasive properties were examined by transwell chamber assay. Western blotting and immunocytochemical staining showed that the expression profiles of KL-6 mucin changed significantly after GalNAc-O-bn treatment. Meanwhile, the invasive ability of Suit-2 cells decreased significantly after GalNAc-O-bn treatment (p < 0.05). These results suggest that glycosylation of KL-6 mucin may be closely related to aggressive behaviors of pancreatic cancer cells like metastasis and invasion.