Can the prognosis of individual patients with nasopharyngeal carcinoma be predicted using a routine blood test at admission?

BACKGROUND AND PURPOSE: We sought to determine the prognostic value of a pre-treatment peripheral blood signature and the peripheral blood signature-based nomogram for patients with non-metastatic nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: We retrospectively collected 21 peripheral blood indicators from patients with NPC between 2004 and 2015. Data were randomly divided into a training and a validation set (ratio: 6:4). The peripheral blood signature was constructed based on candidate biomarkers using the least absolute shrinkage and selection operator Cox regression model. Multivariable logistic regression was applied to identify the independent risk factors of overall survival to build the nomogram. The predictive value of the peripheral blood nomogram was evaluated using time-dependent area under the curve, decision curve analysis, and calibration curve. RESULTS: In total, 6668 patients were enrolled with 4000 and 2668 in the training and validation cohorts, respectively. Four peripheral blood indicators, (white blood cell count, lymphocyte percentage, haemoglobin, and mean platelet volume), were included to construct the peripheral blood signature. Patients were divided into low- and high-risk groups using an optimal cut-off value of - 1.71142. Patients in the high-risk group had significantly lower overall, distant metastasis-free, and progression-free survival than patients in the low-risk group in both cohorts (P < 0.05). We constructed and validated a peripheral blood signature-based nomogram in combination with five vital clinical characteristics, (age, sex, tumour stage, nodal stage, and pre-treatment Epstein-Barr virus DNA), which showed favourable performance. CONCLUSION: Patients with NPC with different outcomes could be distinguished based on their peripheral blood signature score; the proposed peripheral blood signature-based nomogram offers individualised risk estimation.

Research Progress on Anti-tumor Mechanism of Formononetin / 中国实验方剂学杂志

Formononetin is a kind of plant isoflavones extracted from medicinal herbs such as Trifolium pratense，Astragalus membranaceus and Spatholobi Caulis have shown that formononetin has strong anti-tumor biological activity，and can be used as an anti-tumor drug in the treatment of various malignant tumors. Many studies so far have shown that formononetin can inhibit cell proliferation，induce cell apoptosis，inhibit cell migration and invasion，and induce cell cycle arrest on tumors through a variety of molecular mechanisms and pathways. These antitumor activities can be observed in cells of various tumors such as breast cancer，colorectal cancer，prostate cancer，bladder cancer and lung cancer in trials and animal models. Examples of these effects include triggering the generation of reactive oxygen species （ROS），regulating phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin（PI3K/Akt/mTOR） and Mitogen-activated protein kinases（MAPK） signaling pathways，inhibiting the activation of tyrosine kinase（JAK1 and JAK2 ）and nonreceptor tyrosine kinase（c-Src），and regulating cytokeratin 19（CK19），matrix metalloproteinases（MMP），microRNA-21（miR-21），lamin A/C antibody（Lamin A/C），expression of Cyclin D1 and Cyclin E1. In addition， the anti-tumor effects of formononetin derivatives were reviewed in this paper. By modifying the chemical structure of formononetin，many related derivatives have been obtained. Experimental results have shown that some derivatives of formononetin have stronger anti-tumor activity and lower cytotoxicity，but the related molecular mechanism of action still needs to be explored further in-depth. In conclusion，formononetin and its derivatives may become potential anti-tumor drugs.

Research Progress on Lichongtang in Treatment of Uterine Leiomyoma / 中国实验方剂学杂志

Uterine leiomyoma （UL）， the most common benign tumor of the reproductive system in women of childbearing age， is characterized by clinical symptoms such as increased menstrual flow， prolonged menstrual period， breast tenderness，backache， lower abdominal pain and mass in the lower abdomen. With the continuous progress of modern society， the age of women's marriage and childbirth is gradually pushed back， which to a certain extent has led to an increase in the probability of modern women suffering from UL. Relevant literature shows that the incidence of UL is about 70%， and 25%-50% of the patients have clinical symptoms， seriously endangering women's physical health. The prevention and treatment of UL by modern medicine is currently limited to two aspects： drug control of estrogen and progesterone levels and surgical removal. Traditional Chinese medicine（TCM）has shown obvious advantages in improving the clinical symptoms of UL patients， with very broad application prospects as it can regulate body's Qi and blood on the basis of syndrome differentiation， treatment and overall concepts. Lichongtang， as a famous TCM prescription for replenishing Qi， activating blood and removing blood stasis， was created by ZHANG Xi-chun， a famous Chinese medicine doctor in the Qing dynasty， and recorded in the Records of Tradition Chinese and Western Medicine in Combination. It is widely used in the field of gynecological diseases in clinical practice. Studies have shown that Lichongtang is effective in treating UL. Clinical observations show that Lichongtang can significantly relieve the clinical symptoms of UL patients such as prolonged menstrual period， dysmenorrhea， waist and abdomen swelling and irregular vaginal bleeding， with the characteristics of stable curative effect， high safety， less side effect and low recurrence rate. The experimental results show that Lichongtang has a comprehensive regulatory effect on UL through inhibiting the proliferation of UL cells and inducing apoptosis， reducing serum estrogen and progesterone level， regulating the apoptosis pathway of tumor cells， and promoting the degradation of extracellular matrix（ECM）. After retrieval in PubMed， CNKI and other databases， the authors made a review by summarizing the theories， clinical efficacy and action mechanisms of Lichongtang in the treatment of UL， in order to provide reference for the follow-up in-depth study of pharmacological mechanism of Lichongtang and its further clinical application and promotion.

The Desaturase Gene Family is Crucially Required for Fatty Acid Metabolism and Survival of the Brown Planthopper, Nilaparvata lugens.

Desaturases are essentially required for unsaturated fatty acid (UFA) biosynthesis. We identified 10 genes encoding putative desaturases in the transcriptome database of the brown planthopper (BPH), Nilaparvata lugens. These include eight First Desaturase family genes, one cytochrome b5 fused desaturase gene (Nlug-Cytb5r) and one Sphingolipid Desaturase gene (Nlug-ifc). Transcript level profiling revealed significant variation in the expression patterns of these genes across tissues and developmental stages, which occur in a gene-specific manner. Interestingly, their expression was also modulated by the insect food source: the mRNA levels of Nlug-desatC and Nlug-Cytb5r were down-regulated, but the expression level of Nlug-desatA1-b and Nlug-desatA1-c were elevated in the BPH fed on the resistant rice variety Babawee as compared to the non-resistant variety Taichun Native 1 (TN1). Silencing Nlug-desatA1-b, Nlug-desatA1-c, or Nlug-Ifc reduced fatty acid composition and abundance in female BPH 1-d-old-adults compared to controls. Whereas, single knockdown of all ten desaturase genes significantly increased mortality of BPH nymphs compared with controls. Of the ten desaturase genes, knockdown of Nlug-desatA1-b and Nlug-desatA2 caused the highest mortality in BPH (91% and 97%, respectively). Our findings offer a base for expression and functional characterization of newly identified desaturase genes in BPH, and may contribute to RNA interference-based pest management strategies.

Concurrent chemoradiotherapy combined with enteral nutrition support: a radical treatment strategy for esophageal squamous cell carcinoma patients with malignant fistulae.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) significantly increases the survival rate of esophageal squamous cell carcinoma (ESCC) patients with malignant fistulae. Recent clinical evidence has shown the benefits of enteral nutrition for malnourished cancer patients. In this study, we aimed to validate that, with the support of enteral nutrition, ESCC patients who develop malignant fistulae might be able to complete CCRT and achieve long-term survival. METHODS: We reviewed the medical records of 652 patients with ESCC who received definitive CCRT at Sun Yat-sen University Cancer Center between January 2010 and December 2012. Treatment outcome and toxicity were retrospectively evaluated in 40 ESCC patients with malignant fistulae. All the 40 patients were treated with CCRT and evaluated by clinical nutritionists using nutrition risk screening (NRS) before, during, and after treatment. Twenty-two patients received a nasogastric tube, and 18 underwent percutaneous endoscopic gastrostomy feeding. The median energy intake was 2166 kcal/day. Treatment response was evaluated at 3 months after the completion of CCRT. RESULTS: With a median follow-up of 18 months (range, 3-39 months), patients' 1-year overall survival (OS) rate was 62.5%, and the estimated OS time was 25.5 months. Univariate analysis showed that the NRS score (P = 0.003), increase in NRS score (P = 0.024), fistula closure (P = 0.011), and response to treatment (P < 0.001) were significantly associated with OS. Multivariate analysis showed that tumor response (P = 0.044) and increase in NRS score (P = 0.044) were independent predictors of OS. Grade 3 vomiting was observed in 8 patients (20.0%), grade 3 neutropenia was observed in 11 patients (27.5%), and grade 3 cough was observed in 13 patients (32.5%); 2 patients (5.0%) died of massive bleeding during treatment. CONCLUSIONS: CCRT combined with enteral nutrition support is effective for ESCC patients with malignant fistulae. Patients have an increased potential to be cured, especially those who experience complete response and have an increase in NRS score. Careful observation and nutrition support are required for patients with advanced T-category ESCC who undergo CCRT.

Resectable left lower lobe non-small cell lung cancer with lymph node metastasis is related to unfavorable outcomes.

BACKGROUND: Despite numerous previous studies, the consideration of tumor location as a prognostic factor in resectable non-small cell lung cancer (NSCLC) remains controversial. The present study analyzed the association between tumor location and clinical outcome in patients with resectable NSCLC who had undergone lobectomy with systematic lymphadenectomy and who had presented with varying nodal statuses. METHODS: The data from a cohort of 627 eligible patients treated in Sun Yat-sen University Cancer Center between January 2000 and December 2008 were retrospectively collected, and the nodal statuses of patients with different tumor locations were compared. Cox proportional hazards regression model was used to determine the independent factors related to cancer-specific survival (CSS). RESULTS: Multivariate analysis demonstrated that left lower lobe (LLL) tumors [hazard ratio (HR): 1.465, 95% confidence interval (CI) 1.090-1.969, P = 0.011], lymph node metastasis (HR: 2.742, 95% CI 2.145-3.507, P < 0.001), and a tumor size of >4 cm (HR: 1.474, 95% CI 1.151-1.888, P = 0.002) were three independent prognosticators in patients with resectable NSCLC. However, LLL tumors were associated only with CSS in node-positive patients (HR: 1.528, 95% CI 1.015-2.301, P = 0.042), and a tumor size of >4 cm was the only independent risk predictor in the node-negative subgroup (HR: 1.889, 95% CI 1.324-2.696, P < 0.001). CONCLUSIONS: Tumor location is related to the long-term CSS of NSCLC patients with lymph node metastasis. LLL tumors may be upstaged in node-positive patients to facilitate an optimal treatment strategy.

Initial procalcitonin level predicts infection and its outcome in patients with non-Hodgkin lymphoma with febrile neutropenia.

We explored whether initially determined procalcitonin (PCT) levels could facilitate assessment of the risks of infection and death due to treatment failure in patients with non-Hodgkin lymphoma (NHL) with newly developed febrile neutropenia (FN). In the 212 examined episodes, the initial PCT value was markedly higher in patients with microbiologically documented infection (MDI) or clinically documented infection compared with patients with fevers of unknown origin (p < 0.001 for both). Patients with initial PCT values ≥ 0.50 ng/mL were at high risk of MDI (sensitivity 83.5%, specificity 77.2%). A significantly elevated PCT level was closely correlated with patient mortality (area under the curve [AUC] 0.864, 95% confidence interval [CI] 0.811-0.907, p < 0.001) and patients' admission to the intensive care unit (AUC 0.926, 95% CI 0.882-0.957, p < 0.001). In conclusion, the initially determined PCT value was a useful marker for identifying infection and predicting outcome in patients with NHL with FN.

Nutrition support can bring survival benefit to high nutrition risk gastric cancer patients who received chemotherapy.

PURPOSE: The aim of our study is firstly to evaluate the prevalence and prognostic value of nutrition risk in gastric cancer patients and secondly to explore whether the nutrition support can prolong the survival of advanced gastric cancer patients. METHODS: It contained two study periods. In the first period, we prospectively evaluated the nutritional risk of gastric adenocarcinoma patients from 2009 to 2011 using the method of European Nutritional Risk Screening (NRS) 2002. The Kaplan-Meier method and log-rank test were used to evaluate the prognostic value of high nutrition risk. The second period was between 2012 and 2013. We prospectively gave the nutrition support to stage IV gastric cancer patients whose NRS is ≥3. RESULTS: There were 830 patients in the first period, 50.7% patients with a NRS ≥ 3. Patients with NRS ≥ 3 presented a significantly higher percentage of stage IV diseases, elevated values of C-reactive protein, and hypoproteinemia. The median survival was significantly higher in NRS < 3 patients (31.9 vs. 25.7 months, P < 0.001). Multivariate analysis confirmed that NRS status was an independent prognostic factor. There were 347 patients in the second period. Young, male, and good response to chemotherapy were more likely to have the NRS shift to <3 after nutrition support. The median survival was 14.3 and 9.6 months for patients with and without NRS shift, respectively, P = 0.001. CONCLUSIONS: NRS ≥ 3 was an independent adverse prognostic factor in gastric cancer patients. For stage IV patients whose NRS ≥ 3, the nutrition support might be helpful to improve the prognosis.

[Effect of cellular immune supportive treatment on immunity of esophageal carcinoma patients after modern two-field lymph node dissection].

BACKGROUND & OBJECTIVE: Cellular immunity suppression is marked in patients with esophageal carcinoma, which may be resulted temporarily from surgical injury. This study was to evaluate the effect of cellular immune supportive treatment on cellular immunity of patients with esophageal carcinoma. METHODS: A total of 60 patients with thoracic esophageal carcinoma, received two-field dissection, were randomized into control group and trial (immune supportive treatment) group. The patients in trial group were injected with Shenqi injection after operation; the patients in control group received no immune supportive treatment. Peripheral blood samples were obtained before operation, and 3 and 9 days after operation. AgNOR (argyrophilic nucleolar organizer regions) activity in peripheral blood T lymphocytes was measured by tumor immune microphotometry. T cell subsets were measured by flow cytometry. RESULTS: The proportions of CD3+CD4+ and CD4+/CD8+ cells were significantly higher in trial group than in control group at 3 days after operation (P < 0.05). The amount of AgNOR and proportions of CD3+, CD3+CD4+, CD4+/CD8+, and CD4+CD25+ cells were significantly higher in trial group than in control group at 9 days after operation (P < 0.05). There was no significant difference in 1-year survival rate between the 2 groups (P > 0.05). CONCLUSION: Shenqi injection could obviously improve cellular immunity of the esophageal carcinoma patients after modern two-field dissection.

[Perioperative changes of cellular immune response of patients with esophageal carcinoma evaluated through detecting AgNOR content in peripheral blood T lymphocytes and T cell subsets].

BACKGROUND & OBJECTIVE: Patients with esophageal carcinoma often have immunosuppression. This study was to detect perioperative argyrophil nucleolar orgnizer region (AgNOR) content in peripheral blood T lymphocytes and T cell subsets of patients with esophageal carcinoma, investigate the influences of cellular immune condition and surgery on cellular immune function of these patients. METHODS: Peripheral blood samples were obtained from 75 healthy adults and 70 patients with esophageal carcinoma before surgery, 3 and 9 days after surgery. AgNOR content in peripheral blood T lymphocytes was measured by tumor immune microphotometry; T cell subsets was measured by flow cytometry. RESULTS: Before operation, AgNOR content, proportions of CD3(+)CD8(+) and CD8(+)CD25(+) T cells were significantly lower in patients than in healthy controls (P < 0.001); proportions of CD3(+) and CD3(+)CD4(+) T cells of patients were not significantly different from that of healthy controls (P > 0.05); proportions of CD4(+)CD25(+) and CD4(+)/CD8(+) T cells were significantly higher in patients than in healthy controls (P < 0.05). In peripheral blood T lymphocytes of the patients after operation, AgNOR content, CD3(+), CD3(+)CD4+(+), and CD4(+)/CD8(+) T cells were the lowest at the 3rd day, and the highest at the 9th day; CD3(+)CD8(+), CD4(+)CD25(+), and CD8+CD25+ T cells gradually ascended from the 3rd day. At the 9th day after operation, CD3(+) and CD3(+)CD4(+) T cells of patients were not significantly different from that of healthy controls (P> 0.05); AgNOR content, CD3(+)CD8(+) and CD8(+)CD25(+) T cells were still lower in patients than in healthy controls (P<0.05); CD4(+)CD25(+) and CD4(+)/CD8(+) T cells were still higher in patients than in healthy controls (P<0.001). CONCLUSION: Surgery injure may cause temporary cellular immunosuppression in patients with esophageal carcinoma, which slowly recovers early after operation.