Advance on the biology, behaviour ecology and management of the coffee white stem borer, Xylotrechus quadripes Chevrolat, 1863 (Coleoptera: Cerambycidae).

The coffee white stem borer, Xylotrechus quadripes Chevrolat, 1863 (Coleoptera: Cerambycidae) - here removed from the synonymy with X. javanicus (Laporte & Gory, 1841) - is the most notorious pest in Arabica coffee plantations in many southeast Asian countries. It can cause damage up to 80% in various gardens. The borer is reported on 16 different host plants other than coffee. The severity of the pest was more commonly recorded on the Arabica coffee than on other species. More pest intensity on the coffee may be due to its innate evolutionary relation compared to other host plants. Studies revealed that the borer is more specific and attracted to the volatile of coffee plants but it is still needs a strong supporting data. Some of the behavioural and ecological-adaptations of borers leads to avoid predation and chemical-pesticides reaching them. Hence, no single method gives perfect control of this pest; therefore, harmonic use of different tools such as cultural, mechanical, physical, bio-control and chemical methods are the best way to combat this pest. Though the pest is economically important, the information on chemical and ecological behaviour, host plant resistance and recent advancements in the pest management are scanty. The present article is an endeavour to shed a light on biology, behaviour, host selection and management of X. quadripes with multiple instances, that will give a new avenue for the researchers to work on the least concerned fields to develop strong management practice and alert against future pest outbreak.

Selective Electrochemical Halogenation of Functionalized Quinolone.

This work describes an effective C3-H halogenation of quinoline-4(1H)-ones under electrochemical conditions, in which potassium halides serve as both halogenating agents and electrolytes. The protocol provides expedient access to different halogenated quinoline-4(1H)-ones with unique regioselectivity, broad substrate scope, and gram-scale synthesis employing convenient, environmentally friendly electrolysis, in an undivided cell. Mechanism studies have shown that halogen radicals can promote the activation of N-H bonds in quinolones.

Electrochemically Driven Selective Removal of the S═N Bond-Directing Group Using Cyclohexanone Oxime as the Mediator.

An inexpensive electrochemical induction system was used for the efficient reductive defunctionalization of sulfoximines through a radical pathway. This practical and robust strategy could be used for the removal of the S═N bond-directing group from various sulfoximines. The practicability of this method was demonstrated by its mild conditions, simple operation, one-pot procedure, gram-scale synthesis, and the undivided cell. Furthermore, preliminary mechanistic studies suggested that the reaction might proceed via a homocoupling reaction and a denitrification procedure.

Copper-Catalyzed Sulfonylation Reaction of NH-Sulfoximines with Aryldiazonium Tetrafluoroborates and Sulfur Dioxide: Formation of N-Sulfonyl Sulfoximines.

An efficient and practical SO2 insertion protocol of NH-sulfoximines with aryldiazonium tetrafluoroborates and DABSO toward N-sulfonyl sulfoximines has been developed under mildly basic conditions. This transformation features easy operation, readily available substrates, and mild conditions. A tentative mechanism is proposed, which indicates that the aryldiazonium tetrafluoroborates would be radical donors under standard reaction conditions. The aryl radical produced in situ from diazonium salts would be trapped by SO2 to generate an arylsulfonyl radical and then undergo further transformation to generate the final N-sulfonyl sulfoximines.

Copper-Catalyzed Divergent C-H Functionalization Reaction of Quinoxalin-2(1H)-ones and Alkynes Controlled by N1-Substituents for the Synthesis of (Z)-Enaminones and Furo[2,3-b]quinoxalines.

With control by N1-substituents, the switchable divergent C-H functionalization reaction of quinoxalin-2(1H)-ones is achieved for the synthesis of (Z)-enaminones and furo[2,3-b]quinoxalines using the combination of a copper catalyst and an oxidant. This new protocol features mild reaction conditions, readily available materials, and a broad substrate scope. Gram-scale and mechanistic studies were also investigated. Furthermore, the desired products exhibited excellent antitumor activity against A549, HepG-2, MCF-7, and HeLa cells, which were tested by MTT assay.

Impact of apatinib in combination with osimertinib on EGFR T790M-positive lung adenocarcinoma.

BACKGROUND: The purpose of this study was to investigate the anti-tumor activities and the mechanisms of the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib, combined with the anti-angiogenic target drug apatinib, in the treatment of lung adenocarcinoma. We investigated the effects of these drugs in vitro in PC9 (E19 del) and H1975 (E21 L858R/E20 T790M) cell lines, as well as in vivo in both mouse and human experiments. METHODS: PC9 and H1975 cells were cultured in 96-well plates and incubated with osimertinib (1-100 nmol/L), or apatinib (100-1,000 nmol/L), or a combination of the two agents, for 48 h. Cell viability was determined using a Cell Counting Kit-8. The protein expression of EGFR and its downstream signaling pathway members (AKT and ERK) was detected by western blot. For in vivo experiments, BALB/c nude mice were subcutaneously inoculated with H1975 cells in a xenograft model of adenocarcinoma. Mice bearing tumors were treated with osimertinib alone or in combination with apatinib, and tumor growth curves were obtained. Furthermore, we evaluated the efficacy and safety of combined osimertinib and apatinib therapy in three patients with EGFR T790M positive lung adenocarcinoma, who had been previously sensitized to osimertinib but developed an acquired resistance. RESULTS: In vitro experiments revealed that osimertinib combined with apatinib increased the growth inhibition of PC9 and H1975 cells, simultaneously reducing the protein expression of phosphorylated EGFR and its downstream signaling pathway members in H1975 cells, compared to osimertinib treatment alone. In vivo experiments revealed that the combination of osimertinib and apatinib decreased tumor volume in an H1975 cell xenograft model, compared to osimertinib monotherapy at different dosages. All three patients with T790M positive lung adenocarcinoma that progressed following osimertinib treatment responded to continuous osimertinib in combination with apatinib, with a progression-free survival (PFS) range of 5-7 months. CONCLUSIONS: Apatinib can enhance the anti-tumor activity of osimertinib in the treatment of T790M positive lung adenocarcinoma. Further clinical studies are needed to confirm these results.

[Research Advances of Pan-negative Type of Non-small Cell Lung Cancer].

In recent years, series of driver genes, such as EGFR, KRAS/NRAS, BRAF, PIK3CA, ALK and ROS1 and so on, have been found in non-small cell lung cancer (NSCLC) one after another with the development of molecular detecting technology. Targeted drugs bring benefits for these NSCLC patients with driver gene variations. However, some NSCLC did not have any known driver gene variations; we called it pan-negative lung cancer. In this paper, we summarize the concept, clinical pathological characteristics, the epidemiological characteristics, treatment and prognosis of pan-negative NSCLC.

Benefits of postoperative thoracic radiotherapy for small cell lung cancer subdivided by lymph node stage: a systematic review and meta-analysis.

BACKGROUND: Whether postoperative thoracic radiotherapy (PORT) is beneficial for small cell lung cancer (SCLC) of different lymph node stages remains uncertain; therefore, the purpose of this meta-analysis was to explore the clinical significance of PORT for SCLC patients subdivided by lymph node status. METHODS: The PubMed, OVID, Web of SCI, EMBASE, Google Scholar, Cochrane Library, Chinese National Knowledge Infrastructure and Wanfang databases were systematically searched to identify eligible studies where SCLC patients received PORT based on lymph node stage. The main outcome measures were 1-, 3- and 5-year overall survival (OS) rates, as well as 1-, 2- and 3-year local regional recurrence (LRR) rates. All data were analyzed using STATA 12.0 and expressed as risk ratios (RR) with their corresponding 95% confidence intervals (95% CI). RESULTS: Five cohort studies, including 3,497 SCLC patients (578 receiving PORT and 2,919 not) were included in this study. PORT significantly decreased the 1-, 2- and 3-year LRR rates (RR =0.14, 0.28 and 0.27, respectively; Pall<0.05), but did not improve the 1-, 3- or 5-year OS rates when all patients were analyzed together. However, subgroup analysis showed that in the pN0 group PORT did not improve the 1-, 3- or 5-year OS rates or decrease the 1-, 2- or 3-year LRR rates; in the pN1 group PORT reduced the 1-, 2- and 3-year LRR rates (RR =0.11, 0.16 and 0.17, respectively; Pall<0.05) and improved the 1-year OS rate (RR =0.40; P<0.001), but not the 3- or 5-year OS rates; in the pN2 group PORT significantly reduced the 1-, 2- and 3-year LRR rates (RR =0.14, 0.15 and 0.15 respectively; Pall<0.05) and improved the 1-, 3- and 5-year OS rates (RR =0.46, 0.72 and 0.85, respectively; Pall<0.05). CONCLUSIONS: This is the first meta-analysis of the benefits of PORT for SCLC patients. Although derived from retrospective cohort studies, the data showed that PORT significantly reduced the risk of recurrence and improved survival for patients with pN2-SCLC; however, patients with pN0-SCLC did not benefit from PORT, whereas for patients with pN1-SCLC, PORT reduced the LRR rates and improved the 1-year survival rate. The long-term survival benefits of PORT remain unclear and will require further prospective studies.

Meta-analysis of the impact of de novo and acquired EGFR T790M mutations on the prognosis of patients with non-small cell lung cancer receiving EGFR-TKIs.

PURPOSE: The purpose of this meta-analysis was to explore the influences of pretreatment de novo and posttreatment-acquired epidermal growth factor receptor (EGFR) T790M mutations in patients with advanced non-small cell lung cancer (NSCLC) who had received tyrosine kinase inhibitors (TKIs). METHODS: We searched PubMed, Embase, and the China National Knowledge Infrastructure database for eligible literature. Data were extracted to assess the hazard ratios (HRs) for progression-free survival (PFS), overall survival (OS), and post-progression survival (PPS) and the relative ratios (RRs) for objective response rate (ORR). RESULTS: This meta-analysis included 22 studies comprising 1,462 patients with NSCLC who harbored activating EGFR mutations and were treated with EGFR-TKIs. Compared to pretreatment T790M mutation-negative NSCLC, pretreatment T790M mutation-positive NSCLC was associated with decreased PFS (HR 2.23, P<0.001) and OS (HR 1.55, P=0.003). A trend toward significance of worsening ORR (RR 0.86, P=0.051) was evident. The acquired T790M mutation was correlated with improved PFS (HR 0.75, P=0.006) and PPS (HR 0.57, P<0.001), compared to patients without the T790M mutation who progressed after EGFR-TKI treatment. There were no significant differences in OS or ORR between patients with acquired T790M mutation-positive and T790M mutation-negative NSCLC. However, in the tumor tissue rebiopsy subgroup, patients with acquired T790M mutation had improved OS (HR 0.60, P<0.001) compared to T790M mutation-negative patients. In the plasma ctDNA subgroup, acquired T790M mutation decreased the OS (HR 1.87, P<0.001). CONCLUSION: Pretreatment T790M mutation was associated with worse PFS and OS in patients with advanced NSCLC treated with EGFR-TKIs, while acquired T790M mutation was associated with longer PFS and PPS than T790M mutation-negative NSCLC. The effects on OS were different between acquired T790M mutation detected from rebiopsy of tumor tissue and that detected from plasma ctDNA.

Is pulmonary artery a dose-limiting organ at risk in non-small cell lung cancer patients treated with definitive radiotherapy?

PURPOSE: Our previous study suggested that some pulmonary artery (PA) dosimetric parameters were associated with mortality in unresectable non-small cell lung cancer (NSCLC) treated with definitive radiotherapy. The present study aims to analyze the impact of both PA and heart dosimetric parameters on survival of patients with NSCLC treated with definitive conventional fractionated radiotherapy (CFRT) in another independent research center and further determine whether the PA should be considered a dose-limiting organ at risk (OAR) for patients receiving thoracic CFRT. METHODS: We performed a retrospective analysis of successive patients with medically inoperable or unresectable NSCLC treated with definitive radiotherapy or chemoradiotherapy from August 2010 to September 2014. Clinical and pathological information, PA and heart dosimetric factors, and follow-up data were collected from each patient's records and evaluated as potential prognostic factors for survival. Survival probabilities were estimated by the Kaplan-Meier method and compared by the log rank test. Cox proportional hazards regression models were performed to determine the independent predicators of survival. The optimal cutoff points of continuous dosimetric variables were determined by Youden index in receiver operating characteristic (ROC) analysis. RESULTS: This study analyzed the records of 141 patients, 50.4% had adenocarcinoma, 71.6% had stage III disease, and 55% patients received concurrent chemoradiotherapy. Radiation dose ranged from 60 to 76 Gy in 30-38 fractions. Median follow up was 16.9 months. Median overall survival (OS) was 20.5 months (95% confidence interval [CI] 10.3-30.7 months), and 1-, 2-, 3-year OS rates were 75.2%, 58.2% and 56%, respectively. Univariate and multivariate analysis showed that Karnofsky Performance Status (KPS) score, Charlson's Comorbidity Index (CCI), T and N stage, PA invasion grade and the percentage of PA volume that received 40 to 55 Gy (PA V40-55) were significantly associated with OS. No significant associations were found between heart dosimetric factors and OS. Median OS of patients with PA invasion grade 0, 1, 2, and 3 were 41.8, 27.8, 12.7 and 7.5 months, respectively (P < 0.001). PA V40, V45, V50 and V55, using thresholds of 80%, 68%, 45%, and 32%, respectively, were independent predictors for OS. CONCLUSIONS: PA invasion grade and PA V40-55 appear associated with OS in patients with NSCLC treated with definitive CFRT. We propose that PA be considered as a dose-limiting OAR for such patients.

Meta-analysis Exploring the Effectiveness of S-1-Based Chemotherapy for Advanced Non-Small Cell Lung Cancer.

S-1 is a new oral fluoropyrimidine formulation that comprises tegafur, 5-chloro-2,4-dihydroxypyridine, and potassium oxonate. S-1 is designed to enhance antitumor activity and to reduce gastrointestinal toxicity. Several studies have demonstrated that both S-1 monotherapy and S-1 combination regimens showed encouraging efficacies and mild toxicities in the treatment of lung squamous cell carcinoma and adenocarcinoma. However, it is unclear whether S-1 can be used as standard care in advanced non-small cell lung cancer (NSCLC). The purpose of this meta-analysis was to assess the efficacy and safety of S-1-based chemotherapy, compared with standard chemotherapy, in patients with locally advanced or metastatic NSCLC. Thirteen randomized controlled trials (RCTs) involving 2,134 patients with a similar ratio of different pathological types were included. In first-line or second-line chemotherapy, compared with standard chemotherapy, S-1-based chemotherapy showed similar efficacy in terms of median overall survival (mOS), median progression free survival (mPFS), and objective response rate (ORR) (all P > 0.1), and significantly reduced the incidence of grade ≥ 3 hematological toxicities. In patients with locally advanced NSCLC receiving concurrent chemoradiotherapy, compared with standard chemoradiotherapy, significantly improved survival in the S-1-based chemotherapy was noted in terms of mOS and mPFS (risk radio [RR] = 1.289, P = 0.009; RR = 1.289, P = 0.000, respectively) with lower incidence of grade ≥ 3 neutropenia (RR = 0.453, P = 0.000). The present meta-analysis demonstrates that S-1-based chemotherapy shows similar benefits in advanced NSCLC and improves survival in locally advanced NSCLC, compared with standard treatment.

Postoperative radiotherapy and tumor recurrence after complete resection of stage II/III thymic tumor: a meta-analysis of cohort studies.

BACKGROUND: Whether postoperative radiotherapy (PORT) is effective for reducing the recurrence risk in patients who received complete resection of the stage II or III thymic tumors has not been determined. A meta-analysis was performed by combining the results of all available controlled trials. METHODS: PubMed, Cochrane's Library, and the Embase databases were searched for studies which compared the recurrence data for patients with complete resection of the stage II or III thymic tumors assigned to an observing group, or a PORT group. A random effect model was applied to combine the results. RESULTS: Nineteen studies, all designed as retrospective cohort studies were included. These studies included 663 patients of PORT group and 617 patients of observing group. The recurrence rate for the patients in PORT group and observing group were 12.4% and 11.5%, respectively. Results of our study indicated that PORT has no significant influence on recurrent risk in patients with stage II or III thymic tumor after complete resection (odds ratio 1.02, 95% confidence interval 0.55-1.90, P=0.96). When stratified by stages, our meta-analyses did not indicate any significant effects of PORT on recurrent outcomes in either the stage II or the stage III patients. Moreover, subsequent analysis limited to studies only including patients with thymoma or thymic carcinoma also did not support the benefits of PORT on recurrent outcomes. CONCLUSION: Although derived from retrospective cohort studies, current evidence did not support any benefit of PORT on recurrent risk in patients with complete resection of the stage II or III thymic tumors.