Drug therapy for bone metastasis of malignant tumor: theory, progress, and potential.

Bone is a common metastatic site of malignancies, caused by the complex interaction between tumor cells and the bone microenvironment. The complicated procedure covers multiple targets for therapeutic strategies against bone metastasis. At the present, only bisphosphonates and denosumab are currently approved for the prevention of skeletal-related events. But it is still ineffective for some patients, and none of them are proven to prolong the overall survival of patients with bone metastasis. Thus, new bone-modifying agents and therapeutic strategies are required. The review aimed to generalize the basic theory of bone metastasis and major put emphasis on the development of fundamental and potential target drugs in the behavior of bone metastasis. The summary of the drug development process helps to provide ideas for finding new and effective treatments for bone metastasis.

Risk of Immune-Related Pancreatitis in Patients with Solid Tumors Treated with Immune Checkpoint Inhibitors: Systematic Assessment with Meta-Analysis.

We performed a systematic review and meta-analysis to determine the risk of immune-related pancreatitis associated with the treatment by immune checkpoint inhibitors (ICIs) for solid tumors. Eligible studies were selected from multiple databases including phase II/III randomized controlled trials (RCTs) with ICIs in solid tumor patients. The data were analyzed with Stata version 12.0 software. After excluding ineligible studies, a total of 15 clinical trials were considered eligible for the meta-analysis, which included 9099 patients. Compared with chemotherapy or placebo, the risk ratio (RR) for all-grade lipase elevation after CTLA-4 inhibitor treatment was 1.05 (95% confidence interval (CI): 1.01-2.24, p = 0.047). However, the risk for pancreatitis after ICI treatment in any subgroup was not significantly higher than that after control therapy. In addition, compared with ipilimumab/nivolumab alone, the RR for all-grade and high-grade lipase elevation under combination treatment of nivolumab and ipilimumab was 6.43 (95% CI: 1.43-28.99, p = 0.015) and 6.44 (95% CI: 1.39-29.79, p = 0.017), respectively, and the RR for all-grade amylase elevation under combination treatment was 6.08 (95% CI: 1.51-24.44, p = 0.011). Our meta-analysis has demonstrated that both CTLA-4 inhibitors alone and combination treatment of nivolumab and ipilimumab could increase the risk of amylase or lipase elevation, but not significantly increase the risk of pancreatitis when compared with controls.

Perioperative ω-3 Polyunsaturated Fatty Acid Nutritional Support in Gastrointestinal Cancer Surgical Patients: A Systematic Evaluation.

This study was a systematic evaluation of the beneficial effects of n-3 polyunsaturated fatty acid (PUFA) in abdominal cancer surgical patients. A literature search of the databases PubMed, Medline, Cochrane, and EMBASE was conducted for studies published up to November 2014 in English language journals. Randomized controlled trials (RCTs) examining the effects of n-3 PUFA intake relative to conventional nutrition in surgical patients were included. The main outcomes were the duration of systemic inflammatory response syndrome (SIRS), length of hospital stay (LOS), serum C-reactive protein (CRP) levels, and postoperative complications. We identified 15 RCTs among 158 relevant trials. The results indicated the associations between n-3 PUFA intake and reduced LOS [mean differences (MDs), -2.47 d; 95% confidence intervals (CIs), -3.25 to -1.69], duration of SIRS (MD, -0.57 d; 95% CI, -0.92 to -0.22), and serum CRP levels (MD, -3.97 mg/l; 95% CI, -7.88 to -0.07) compared with consumption of conventional nutrition, as well as reduced incidence of postoperative infectious complications (risk ratio, 0.66; 95% CI, 0.49-0.87). This systematic evaluation suggests that n-3 PUFA significantly reduces the postoperative infectious complication rate, and shortens hospitalization and SIRS duration, particularly in malnourished gastrointestinal cancer patients.

Clinicopathological characteristics and treatment outcomes of Chinese patients with genitourinary embryonal rhabdomyosarcoma.

BACKGROUND: Genitourinary embryonal rhabdomyosarcoma is rarely reported in China. This retrospective analysis aimed to characterize the clinicopathologic features and treatment outcomes of genitourinary embryonal rhabdomyosarcoma in a sample of Chinese patients. METHODS: Basic demographic and clinical data of 29 patients, who were diagnosed with genitourinary embryonal rhabdomyosarcoma between January 2000 and December 2011, were retrieved and analyzed. RESULTS: In these patients, 25 were males and 4 were females with a median age of 12 years. Paratesticule was the most common lesion site, followed by the prostate, bladder, and vagina. The median tumor size was 5.80 cm. Six patients had clinically positive regional nodes. At the initial diagnosis, patients had a metastatic disease. According to the TNM staging classification for the IRS-IV, phase I lesions were detected in ten cases, phase II lesions in six cases, phase III lesions in four cases, and phase IV lesions in nine cases. The median survival of all patients was 63 (range from 6 to 118) months. The 1-, 3-, and 5-year survival rates for these patients were 93%, 83%, and 52%, respectively. Multivariate analyses demonstrated that staging and anemia were significant predictors of prognosis. CONCLUSIONS: Our findings suggest that metastasis predicts a poor prognosis. Chemotherapy played an important role in comprehensive treatment. Palliative and neo-adjuvant chemotherapy could increase median survival time.

The consumption of omega-3 polyunsaturated fatty acids improves clinical outcomes and prognosis in pancreatic cancer patients: a systematic evaluation.

This study was aimed to systematically evaluate results of trials examining the effects of omega-3 polyunsaturated fatty acid (n-3 PUFA) consumption on body weight, lean body mass, resting energy expenditure, and overall survival in pancreatic cancer patients. We searched Medline, Pubmed, Embase, and Cochrane databases. We selected randomized controlled trials of n-3 PUFA vs. conventional nutrition in unresectable pancreatic cancer patients. We analyzed our data using the Cochrane statistical package RevMan 5.1. Eleven trials met our inclusion criteria. There was a significant increase in body weight [weighted mean difference (WMD) = 0.62; 95% confidence interval (CI), 0.54-0.69, P < 0.00001) and lean body mass (WMD = 0.96; 95% CI, 0.86-1.06, P < 0.00001), a significant decrease in resting energy expenditure (WMD = -29.74; 95% CI, -55.89-3.59, P = 0.03), and an increase in overall survival (130-259 days vs. 63-130 days) in unresectable pancreatic cancer patients who consumed an oral nutrition supplement enriched with n-3 PUFAs compared to those who consumed conventional nutrition. This preliminary study suggests that n-3 PUFAs are safe and have a positive effect on clinical outcomes and survival in pancreatic cancer patients.

Prognostic factors in older patients with advanced non-small cell lung cancer in China.

AIMS AND BACKGROUND: The human life expectancy and the incidence of lung cancer have increased dramatically in recent years. As a result, there is a high demand for the management of older patients with advanced non-small cell lung cancer (NSCLC) in clinical practice. The purpose of this study is to evaluate the prognostic factors in ≥65-year-old patients with advanced NSCLC in China. METHOD: This study involved a retrospective review of 78 ≥65-year-old patients with a diagnosis of NSCLC and at an advanced stage of disease, defined as stage IIIB or IV. All patients were followed up for a 3-year interval to determine the survival rates. Clinical data including gender, smoking history, comorbidities, performance status (PS), histological differentiation, disease stage, treatment and overall survival were recorded. The log-rank test was used to calculate survival rates. Multivariate Cox regression analysis was performed to determine independent prognostic factors. RESULTS: The 1-year, 2-year and 3-year survival rates of the 78 patients were 44.9%, 23.1% and 9.0%, respectively. In univariate analysis by the log-rank test, the 3-year survival rate was significantly associated with PS (P <0.01), disease stage (P <0.01) and chemotherapy treatment (P <0.01). The results of multivariate Cox regression analysis confirmed that PS and disease stage were independent prognostic factors. CONCLUSION: The 3-year survival rate in ≥65-year-old patients with advanced NSCLC was significantly associated with PS, disease stage and chemotherapy. PS and disease stage were independent prognostic factors. Older patients with advanced NSCLC in China might benefit from chemotherapy.

Correlation of transforming growth factor beta-1 gene polymorphisms C-509T and T869C and the risk of gastric cancer in China.

BACKGROUND AND AIM: As an important cytokine that modulate the cell cycle, the involvement of transforming growth factor beta-1 (TGF-beta1) in carcinogenesis has been extensively studied for many years. Literatures have demonstrated that TGF-beta1 gene polymorphisms may alter the risk of various cancers, such as lung, prostate and breast. To investigate whether polymorphisms of the TGF-beta1 gene can modify the risk of gastric cancer, we conduct this hospital-based, case-control study. METHODS: One hundred and sixty-seven cases and 193 gender, age-matched healthy controls were enrolled in this case-control study. TGF-beta1 polymorphisms C-509T and T + 869C were identified by PCR-RFLP and ARMS-PCR protocols, respectively. RESULTS: Significantly different distributions of both genes were demonstrated between the case and control. Variant genotypes -509CT, -509TT, +869TC and +869CC were associated with increased risk of gastric cancer (P = 0.001, OR = 2.54; P = 0.016, OR = 2.09; P < 0.001, OR = 3.46; P < 0.001, OR = 4.04, respectively). With haplotype analysis, wild type CT (-509C and +869T) led to a lower frequency in case than that in control (P < 0.001), while haplotype TC was more frequent in case than in control (P < 0.001). Multiple logistic regression analysis revealed that individuals with haplotype TC had an increased likelihood of developing gastric cancer (OR = 3.19, 95%CI = 1.72-5.90). CONCLUSIONS: Our findings imply that -509C > T and +869T > C gene polymorphisms in TGF-beta1 may be a critical risk factor of genetic susceptibility to gastric cancer in the Chinese population.

[Detection and classification of Mycoplasma in cell lines].

OBJECTIVE: To detect the rate of Mycoplasma infection in cell lines and further determine its types. METHODS: We performed nest PCR amplification of Mycoplasma's conserved regions (16S-23S) and sequenced the spacer with different length between conserved regions. RESULTS: Within the tested 22 cell lines, 17 (77.3%) showed Mycoplasma infections, of which 5 had two or more types of Mycoplasma. M. fermentans and hyorhinis were more frequently detected within the types of infected Mycoplasma. CONCLUSION: The high rate of Mycoplasma infection in cell lines makes it necessary for researchers to pay more attention to its influence on research data when using cell lines as models. Establishment of detection and classifying techniques make it possible to further study the pathogenesis of different types of Mycoplasma.

[Relationship between polymorphism of IRF-3 gene codon 427 and esophageal cancer in Anyang population of China].

OBJECTIVE: To investigate the association between the single nucleotide polymorphisms (SNPs) of interferon regulatory factor 3 (IRF-3) gene and the susceptibility of esophageal cancer in Anyang area, Henan Province. METHODS: The genomic DNAs of 152 esophageal cancer patients and 191 health controls were extracted from the peripheral blood leukocytes. Three fragments covering codons 96, 194, 377, and 427 of the IRF-3 gene were amplified by polymerase chain reaction (PCR). The SNPs were revealed by DNA sequencing and the genotype of every sample was determined accordingly. The frequency distribution of the SNPs was analyzed by chi(2) test. RESULTS: There were no IRF-3 gene SNPs at codons 96, 194, or 377 in Anyang participants. There was significant difference in the SNPs at codon 427 between the healthy controls and esophageal cancer patients in Anyang area OR=2.38 (95%CI=1.15-4.95,P<0.05). CONCLUSION: The SNPs at codon 427 of the IRF-3 gene may relate to the susceptibility of esophageal cancer. The risk of esophageal cancer in participants with C allele is 2.38-fold compared to those with G allele.