The Efficacy and Safety of Anlotinib Plus Etoposide with Cisplatin/Carboplatin in the First-Line Treatment of Lung Cancer: A Phase II Clinical Study.

Background: The primary aim of this phase II clinical study was to assess the safety and efficacy of combining anlotinib, etoposide, and platinum-based drugs as a first-line treatment for ES-SCLC. Methods: Patients underwent the standard chemotherapeutic regimen, consisting of four courses of etoposide plus cisplatin/carboplatin. Additionally, each patient received a 2-week intervention with anlotinib (12 mg/day, once daily). Anlotinib was continued until disease progression, occurrence of unbearable adverse events (AEs), or withdrawal from the research. Progression-free survival (PFS) served as the primary prognostic measure. Secondary measures included the disease control rate (DCR), objective response rate (ORR), overall survival time (OS), and the incidence of AEs. Results: The DCR and ORR were 97.6% and 91.0%, respectively. Estimated PFS and OS were 5.0 months (95% CI: 1.0-10.8 months) and 13.0 months (95% CI: 8.4-18.6 months), respectively. No unexpected adverse effects were reported during the trial. The most common adverse reactions included anemia (42.22%), hypertension (53.33%), alopecia (40.00%), elevated transaminase (24.40%), and elevated alkaline phosphatase (24.44%). Sixteen cases (35.56%) were classified as AEs of grades 3-5. No deaths attributed to treatment-related causes occurred in any patient during the trial. Conclusion: Combination chemotherapy is currently the first-line therapy for extensive small-cell lung cancer (ES-SCLC). Combining anlotinib with conventional platinum-based chemotherapy demonstrated promising therapeutic outcomes and prognosis in the management of ES-SCLC.

Clinical profiles and outcomes of acute type A aortic dissection and intramural hematoma in the current era: lessons from the first registry of aortic dissection in China.

BACKGROUND: Acute type A aortic dissection (ATAAD) and acute type A intramural hematoma (ATAIMH) are life-threatening diseases with high mortality. To better understand their clinical features in the Chinese population, we analyzed the data from the first Registry of Aortic Dissection in China (Sino-RAD) to promote the understanding and management of the diseases. METHODS: All patients with ATAAD and ATAIMH enrolled in Sino-RAD from January 1, 2012 to December 31, 2016 were involved. The data of patients' selection, history, symptoms, management, outcomes, and postoperation complications were analyzed in the study. The continuous variables were compared using the Student's t test for normal distributions and the Mann-Whitney U test for non-normal distributions. Categorical variables were compared using the Chi-square test or Fisher exact test. RESULTS: A total of 1582 patients with ATAAD and 130 patients with ATAIMH were included. The mean age of all patients was 48.4 years. Patients with ATAAD were significantly younger than patients with ATAIMH (48.9 years vs. 55.6 years, P < 0.001). For the total cohort, males were dominant, but the male ratio of patients with ATAAD was significantly higher compared to those with ATAIMH (P = 0.01). The time range from the onset of symptom to hospitalization was 2.0 days. More patients of ATAIMH had hypertension than that of ATAAD (82.3% vs. 67.6%, P < 0.05). Chest and back pain were the most common clinical symptoms. Computerized tomography (CT) was the most common initial diagnostic imaging modality. 84.7% received surgical treatment and in-hospital mortality was 5.3%. Patients with ATAAD mainly received surgical treatment (89.6%), while most patients with ATAIMH received medical treatment (39.2%) or endovascular repair (35.4%). CONCLUSIONS: Our study suggests that doctors should comprehensively use clinical examination and genetic background screening for patients with ATAAD and ATAIMH and further shorten the time range from symptoms onset to intervention, achieving early diagnosis and treatment, thereby reducing the mortality rate of patients with aortic dissection in China. We should standardize the procedures of aortic dissection treatment and improve people's understanding. Meanwhile, the curing and transferring efficiency should also be improved.

MiR-454 prompts cell proliferation of human colorectal cancer cells by repressing CYLD expression.

Previous studies have shown that miR-454 plays an important role in a variety of biological processes in various human cancer cells. However, the underlying mechanisms of this microRNA in colorectal cancer (CRC) cells remain largely unknown. In the present study, we investigated the miR-454 role in CRC cell proliferation. We found that miR-454 expression is markedly upregulated in CRC tissues and CRC cells compared with the matched tumor adjacent tissues and the FHC normal colonic cell line. Ectopic expression of miR-454 promoted the proliferation and anchorage-independent growth of CRC cells, whereas inhibition of miR-454 reduced this effect. Bioinformatics analysis further revealed cylindromatosis (CYLD), a putative tumor suppressor as a potential target of miR-454. Data from luciferase reporter assays showed that miR-454 directly binds to the 3'-untranslated region (3'-UTR) of CYLD mRNA and repressed expression at both transcriptional and translational levels. In functional assays, CYLD-silenced in miR-454-in-transfected SW480 cells have positive effect to promote cell proliferation, suggesting that direct CYLD downregulation is required for miR-454-induced CRC cell proliferation. In sum, our data provide compelling evidence that miR-454 functions as an onco-miRNA, playing a crucial role in the promoting cell proliferation in CRC, and its oncogenic effect is mediated chiefly through direct suppression of CYLD expression.

Combining bevacizumab and panitumumab with irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) as second-line treatment in patients with metastatic colorectal cancer.

Bevacizumab and panitumumab are human monoclonal antibodies with different targeting antigens, vascular endothelial growth factor, and epidermal growth factor receptor. This study examined the efficacy and safety of combining bevacizumab and panitumumab plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) as the second-line therapy for patients with metastatic colorectal cancer (mCRC). Patients with mCRC, and previously failed with oxaliplatin-based chemotherapy, were given bevacizumab (3 mg/kg) and panitumumab (3 mg/kg) plus FOLFIRI every other week. From September 2008 to July 2012, 173 patients were included in the study. The response rate was 42.3 %, and the disease-controlled rate was 65.7 %. The median progression-free survival was 6.5 months, and the median overall survival was 15.4 months. Various adverse events (AE) including those known toxicities associated with antibody therapy were recorded. The overall AE rate was 64.5 % for grade 3-4. The treatment of combining bevacizumab and panitumumab plus FOLFIRI is effective and safe as a second-line therapy for patients with mCRC.

Pigment epithelium-derived factor promotes Fas-induced cardiomyocyte apoptosis via its receptor phospholipase A2.

AIMS: Cardiovascular diseases cause significant morbidity and mortality worldwide. Recently, our research team demonstrated that a multifunctional cytokine, pigment epithelium-derived factor (PEDF), plays a critical role in regulating myocardial infarction. However, few researchers have studied the molecular mechanisms by which PEDF and its receptors influence the pathophysiology of cardiovascular disease. We tested the hypothesis that PEDF affects cardiomyocyte apoptosis under hypoxic conditions and determined the role that its receptors phospholipase A2 (PLA2) and laminin receptor play in this process. MAIN METHODS: Cardiomyocytes were isolated from neonatal mice and treated with PEDF under normoxic and hypoxic conditions; then, apoptosis was assessed using Annexin V/PI staining and flow cytometry. Western blotting and immunofluorescence staining were used to detect PEDF receptor expression, and siRNA knockdown of PEDF receptors was performed to determine which receptor was involved in mediating cardiomyocyte apoptosis. KEY FINDINGS: Our results demonstrated that PEDF increased cardiomyocyte apoptosis during hypoxia via Fas and that PEDF receptors were expressed on cardiomyocyte cell membranes. Furthermore, siRNA experiments indicated that the PEDF receptor PLA2 was responsible for inducing cardiomyocyte apoptosis via the Fas pathway. SIGNIFICANCE: PEDF promoted Fas-induced cardiomyocyte apoptosis via its receptor PLA2.

Bone marrow-derived cells in neovascular age-related macular degeneration: contribution and potential application.

Neovascular age-related macular degeneration, characterized by the formation of choroidal neovascularization (CNV), is a predominant cause of serious loss of vision. The pathogenesis of CNV is complex and still imperfectly understood. Prior studies have shown that bone marrow-derived cells (BMC) play a role in CNV. In this review article, we describe the contribution of BMC to CNV development, and discuss the potential use of BMC in the anticipation and treatment of CNV-associated diseases as well as research needs in the future.

A therapeutic strategy for choroidal neovascularization based on recruitment of mesenchymal stem cells to the sites of lesions.

Choroidal neovascularization (CNV) is a common cause of severe and irreversible visual loss; however, the treatment of CNV has been hindered by its complex and poorly understood pathogenesis. It has been postulated that bone marrow (BM)-derived cells (BMCs) contribute to CNV, but little is known about the role of mesenchymal stem cells (MSCs) in CNV and their therapeutic potential for CNV treatment. We found that BM-derived MSCs transplanted by intravenous injection into laser-induced CNV mouse models were specifically recruited into CNV lesions, where they differentiated into multiple cell types and participated in the development of neovascularization, without stagnation in other organs. By taking advantage of this recruitment potential, engineered MSCs were used to produce the antiangiogenic pigment epithelial-derived factor (PEDF) at the CNV sites, thereby inhibiting the growth of CNVs and stimulating regressive features. Further studies indicated that the effect may be mediated, at least partly, by retinal pigment epithelial (RPE) cells, which function as important regulators for CNV development. These results suggest that MSCs contribute to CNV and could serve as delivery vehicles of antiangiogenic agents for the treatment of a range of CNV-associated diseases.

A clinical trial of combined use of rosiglitazone and 5-aminosalicylate for ulcerative colitis.

AIM: To investigate the therapeutic effects of the combined use of rosiglitazone and aminosalicylate on mild or moderately active ulcerative colitis (UC). METHODS: According to the national guideline for diagnosis and treatment of inflammatory bowel disease (IBD) in China, patients with mild or moderately active UC in our hospital were selected from July to November, 2004. Patients with infectious colitis, amoebiasis, or cardiac, renal or hepatic failure and those who had received corticosteroid or immunosuppressant treatment within the last month were excluded. Following a quasi-randomization principle, patients were allocated alternatively into the treatment group (TG) with rosiglitazone 4 mg/d plus 5-ASA 2 g/d daily or the control group (CG) with 5-ASA 2 g/d alone, respectively, for 4 wk. Clinical changes were evaluated by Mayo scoring system and histological changes by Truelove-Richards' grading system at initial and final point of treatment. RESULTS: Forty-two patients completed the trial, 21 each in TG and CG. The Mayo scores in TG at initial and final points were 5.87 (range: 4.29-7.43) and 1.86 (range: 1.03-2.69) and those in CG were 6.05 (range: 4.97-7.13) and 2.57 (range: 1.92-3.22) respectively. The decrements of Mayo scores were 4.01 in TG and 3.48 in CG, with a remission rate of 71.4% in TG and 57.1% in CG, respectively. Along with the improvement of disease activity index (DAI), the histological grade improvement was more significant in TG than in CG (P < 0.05). CONCLUSION: Combined treatment with rosiglitazone and 5-ASA achieved better therapeutic effect than 5-ASA alone without any side effects. Rosiglitazone can alleviate colonic inflammation which hopefully becomes a novel agent for UC treatment.

[A clinical trial of rosiglitazone and 5-aminosalicylate combination for ulcerative colitis].

OBJECTIVE: To investigate the therapeutic effects of the combination of rosiglitazone, which is peroxisome proliferators-activated receptor gamma (PPARgamma) ligands used to treat type 2 diabetes mellitus, and aminosalicylate on mildly or moderately active ulcerative colitis and on relevant cytokine expressions. METHODS: According to the national guideline of China for diagnosis and treatment of the inflammatory bowel disease (IBD), 42 patients with mild, moderately active ulcerative colitis were selected from the outpatient clinic of West China Hospital from July to November, 2004. Patients with infectious colitis, amoebiasis, or cardiac, renal or hepatic failure were excluded, as well as those who had received corticosteroid or immunosuppressant treatment within the last month. Following a quasi-randomization principle, patients were allocated alternatively into the treatment group with rosiglitazone 4 mg/d plus 5-aminosalicylic acid (5-ASA) 2 g/d or sulfasalazine 3 g/d and the control group with 5-ASA or sulfasalazine alone for 4 weeks. Clinical and histological changes were evaluated weekly by the Mayo scoring system for assessment of the activity of ulcerative colitis and the Truelove-Richards' grading system, respectively. PPARgamma and nuclear factor (NF)-kappaB p65 expressions in colonic mucosa were investigated before and after the treatment. RESULTS: Mayo scores decreased 4.01 in treatment group and 3.48 in control group respectively, with a remission rate 71.4% in treatment group and 57.1% in control group respectively. Along with the improvement of the Mayo score, the histological grade improvement was more significant in treatment group than in control group (P < 0.05). PPARgamma expression was higher, and NF-kappaB p65 positive rate was lower in treatment group than in control group after the treatment, and there was a good negative correlation between PPARgamma and NF-kappaB. CONCLUSIONS: Combined treatment with rosiglitazone and 5-ASA achieved better therapeutic effect than 5-ASA alone without any side effects. The PPARgamma expression was lower in active ulcerative colitis. Rosiglitazone alleviate colonic inflammation probably the through blockade of NF-kappaB, which can be a novel approach to the ulcerative colitis treatment.

[The clinical, pathological features and expression of Ki-67 and COX-2 in severe reflux esophagitis and Barrett's esophagus].

OBJECTIVE: To study the clinical, pathological features of severe reflux esophagitis (SRE) and Barrett's esophagus (BE) and search for expression and significance of Ki-67 and COX-2 in their tissues. METHODS: Both SRE (n = 15) and BE (n = 25) cases were retrospectively analyzed for clinical manifestations, endoscopic findings and pathological features. The expression levels of Ki-67 and COX-2 of esophageal epithelium in the two groups were compared with that of normal esophageal (NE) epithelium (n = 10) by immunoperoxidase staining. RESULTS: It was found that the positivity and staining intensity of Ki-67 expression in SRE and BE were higher than those in normal esophageal epithelium (P<0.01), but there were no statistical differences between these two groups (P>0.05); COX-2 was selectively expressed in some BE epithelium, but not in SRE and normal esophageal epithelium. CONCLUSION: There were intensified Ki-67 expressions in the epithelium of SRE and BE, which could help us to evaluate the prognosis of gastroesophageal reflux disease (GERD) patients clinically by surveillance of Ki-67. COX-2 was selectively expressed in BE epithelium, so COX-2 inhibitors may have the potential for treatment of BE and for chemoprevention of its malignant change.