Penpulimab, an anti-PD-1 antibody, for heavily pretreated metastatic nasopharyngeal carcinoma: a single-arm phase II study.

Penpulimab is an anti-programmed cell death-1 (PD-1) IgG1 antibody with no Fc gamma receptor (FcγR) binding activity, and thus theoretically reduced immune-related adverse events (irAEs) while maintaining efficacy. This single-arm, phase II trial conducted across 20 tertiary care centers in China enrolled adult patients with metastatic nasopharyngeal carcinoma (NPC) who had failed two or more lines of previous systemic chemotherapy. Patients received 200-mg penpulimab intravenously every 2 weeks (4 weeks per cycle) until disease progression or intolerable toxicities. The primary endpoint was objective response rate (ORR) per RECIST (version 1.1), as assessed by an independent radiological review committee. The secondary endpoints included progression-free survival (PFS) and overall survival (OS). One hundred thirty patients were enrolled and 125 were efficacy evaluable. At the data cutoff date (September 28, 2022), 1 patient achieved complete response and 34 patients attained partial response. The ORR was 28.0% (95% CI 20.3-36.7%). The response was durable, with 66.8% still in response at 9 months. Thirty-three patients (26.4%) were still on treatment. The median PFS and OS were 3.6 months (95% CI = 1.9-7.3 months) and 22.8 months (95% CI = 17.1 months to not reached), respectively. Ten (7.6%) patients experienced grade 3 or higher irAEs. Penpulimab has promising anti-tumor activities and acceptable toxicities in heavily pretreated metastatic NPC patients, supporting further clinical development as third-line treatment of metastatic NPC.

Azaphilone pigments from the marine-derived Penicillium sclerotium UJNMF 0503 and their neuroprotective potential against H2O2-induced cell apoptosis through modulating PI3K/Akt pathway.

Azaphilones represent a particular group of fascinating pigments from fungal source, with easier industrialization and lower cost than the traditional plant-derived pigments, and they also display a wide range of pharmacological activities. Herein, 28 azaphilone analogs, including 12 new ones, were obtained from the fermentation culture of a marine fungus Penicillium sclerotium UJNMF 0503. Their structures were elucidated by MS, NMR and ECD analyses, together with NMR and ECD calculations and biogenetic considerations. Among them, compounds 1 and 2 feature an unusual natural benzo[d][1,3]dioxepine ring embedded with an orthoformate unit, while 3 and 4 represent the first azaphilone examples incorporating a novel rearranged 5/6 bicyclic core and a tetrahydropyran ring on the side chain, respectively. Our bioassays revealed that half of the isolates exhibited neuroprotective potential against H2O2-induced injury on RSC96 cells, while compound 13 displayed the best rescuing capacity toward the cell viability by blocking cellular apoptosis, which was likely achieved by upregulating the PI3K/Akt signaling pathway.

Accumulation of ß-aminoisobutyric acid mediates hyperalgesia in ovariectomized mice through Mas-related G protein-coupled receptor D signaling.

Hyperalgesia is typified by reduced pain thresholds and heightened responses to painful stimuli, with a notable prevalence in menopausal women, but the underlying mechanisms are far from understood. ß-Aminoisobutyric acid (BAIBA), a product of valine and thymine catabolism, has been reported to be a novel ligand of the Mas-related G protein coupled receptor D (MrgprD), which mediates pain and hyperalgesia. Here, we established a hyperalgesia model in 8-week-old female mice through ovariectomy (OVX). A significant increase in BAIBA plasma level was observed and was associated with decline of mechanical withdrawal threshold, thermal and cold withdrawal latency in mice after 6 weeks of OVX surgery. Increased expression of MrgprD in dorsal root ganglion (DRG) was shown in OVX mice compared to Sham mice. Interestingly, chronic loading with BAIBA not only exacerbated hyperalgesia in OVX mice, but also induced hyperalgesia in gonadally intact female mice. BAIBA supplementation also upregulated the MrgprD expression in DRG of both OVX and intact female mice, and enhanced the excitability of DRG neurons in vitro. Knockout of MrgprD markedly suppressed the effects of BAIBA on hyperalgesia and excitability of DRG neurons. Collectively, our data suggest the involvement of BAIBA in the development of hyperalgesia via MrgprD-dependent pathway, and illuminate the mechanisms underlying hyperalgesia in menopausal women.

First-line treatment of driver gene-negative metastatic lung adenocarcinoma with malignant pleural effusion: Should chemotherapy be combined with an immune checkpoint inhibitor or bevacizumab?

Patients with metastatic lung adenocarcinoma (MLA) and malignant pleural effusion (MPE) without driver gene mutations have a poor prognosis. None of the standard treatment strategies is recommended for such patients. We retrospectively analyzed the efficacy of the first-line treatment for this specific population: standard platinum-based doublet chemotherapy (CT), CT plus an immune checkpoint inhibitor (CT plus ICI), and CT plus bevacizumab (CT plus Bev). A total of 323 eligible patients were enrolled: CT alone (n = 166), CT plus Bev (n = 72), and CT plus ICI (n = 85). Treatment efficacy assessments were performed every two cycles according to the RECIST guidelines. The endpoints were overall survival (OS) and progression-free survival (PFS). Kaplan-Meier (K‒M) curves and the log-rank test were used to compare OS and PFS. p < 0.05 was the threshold of significance (statistical software: SPSS). The median follow-up was 11.4 months (range, 2.1-49.6 months). PFS and OS in the CT plus ICI/CT plus Bev cohort were significantly longer than those in the CT group (PFS: 7.8/6.4/3.9 months, p < 0.0001; OS: 16.4/15.6/9.6 months, p < 0.0001, respectively). CT plus Bev had better PFS and OS than CT plus ICI/CT in PD-L1 < 1% patients (PFS: 8.4/5.0/3.8 months, p < 0.0001; OS: 15.6/12.9/9.3 months, p < 0.0001). Among patients with PD-L1 1-49%, CT plus ICI led to a longer PFS and OS (PFS: 8.9/5.8/4.2 months, p = 0.009; OS: 24.2/18.8/11.5 months, p = 0.03). In the cohort with PD-L1 ≥ 50%, CT plus ICI was still the best first-line treatment (PFS: 19.7/13.8/9.6 months, p = 0.033; OS: 27.2/19.6/14.9 months, p = 0.047). In driver gene-negative MLA with MPE, CT plus Bev or ICI better controlled MPE and significantly prolonged survival compared to CT alone. PD-L1 expression (negative/positive) may be a key factor influencing the choice of CT plus Bev or ICI.

Tanshinone IIA attenuates osteoarthritis via inhibiting aberrant angiogenesis in subchondral bone.

Excessive angiogenesis in subchondral bone is a pathological feature of osteoarthritis (OA). Tanshinone IIA (TIIA), an active compound found in Salvia miltiorrhiza, demonstrates significant anti-angiogenic properties. However, the effect of TIIA on abnormal subchondral angiogenesis in OA is still unclear. This study aims to investigate the mechanism of TIIA in modulating subchondral bone angiogenesis during OA and assess its therapeutic potential in OA. Our findings demonstrate that TIIA attenuated articular cartilage degeneration, normalized subchondral bone remodeling, and effectively suppressed aberrant angiogenesis within subchondral bone in monosodium iodoacetate (MIA)-induced OA mice. Additionally, the angiogenesis capacity of primary CD31hiEmcnhi endothelial cells was observed to be significantly reduced after treatment with TIIA in vitro. Mechanically, TIIA diminished the proportion of hypertrophic chondrocytes, ultimately leading to a substantial reduction in the secretion of vascular endothelial growth factor A (VEGFA). The supernatant of hypertrophic chondrocytes promoted the tube formation of CD31hiEMCNhi endothelial cells, whereas TIIA inhibited this process. Furthermore, TIIA effectively suppressed the expression of vascular endothelial growth factor receptor 2 (VEGFR2) along with its downstream MAPK pathway in CD31hiEmcnhi endothelial cells. In conclusion, our data indicated that TIIA could effectively inhibit the abnormal angiogenesis in subchondral bone during the progression of OA by suppressing the VEGFA/VEFGR2/MAPK pathway. These findings significantly contribute to our understanding of the abnormal angiogenesis in OA and offer a promising therapeutic target for OA treatment.

Pericardial irradiation dose may be strongly associated with grade 4 lymphopenia and affect prognosis in patients with locally advanced esophageal cancer receiving definitive concurrent chemoradiotherapy.

BACKGROUND: The immune system may influence prognosis, and lymphopenia is a frequent side effect of concurrent chemoradiotherapy (CCRT). Radical irradiation for locally advanced esophageal cancer (LA-EC) exposes significant vascular and heart volumes. In this study, we hypothesized that lymphopenia is linked to cardiac and pericardial doses and affects patient prognosis. METHODS AND MATERIALS: We identified 190 LA-EC patients who received radical CCRT. Multivariate analysis (MVA) was performed to correlate clinical factors and dosimetric parameters with overall survival (OS). We collected lymphocyte-related variables and ratios before and during CCRT. MVA was performed to correlate hematologic toxicity with OS. The relationship between dosimetric parameters and G4 lymphopenia was determined using logistic stepwise regression. Finally, a nomogram of G4 lymphopenia was developed and validated externally. RESULTS: Median follow-up time for all patients was 27.5 months. On MVA for OS, higher pericardial V30 (PV30 ) was linked to worse survival (HR: 1.013, 95% CI: 1.001-1.026, p = 0.039). The median OS stratified by PV30 > 55.3% and PV30 ≤ 55.3% was 24.0 months and 54.0 months, respectively (p = 0.004). G4 lymphopenia was shown to be linked with worse OS in the MVA of hematological toxicity with OS (HR: 2.042, 95% CI: 1.335-3.126, p = 0.001). Thirty of the 100 patients in the training set had G4 lymphopenia. Logistic stepwise regression was used to identify variables associated with G4 lymphopenia, and the final model consisted of stage-IVA (p = 0.017), platelet-to-lymphocyte ratio during CCRT (p = 0.008), Heart V50 (p = 0.046), and PV30 (p = 0.048). Finally, a nomogram predicting G4 lymphocytopenia were constructed and externally validated. The ROC curve showed an AUC for internal validation of 0.775 and external validation of 0.843. CONCLUSION: Higher doses of pericardial radiation might affect LA-EC patients' prognosis by inducing G4 lymphopenia during CCRT. Further prospective studies are warranted to confirm these findings, especially in the era of immune-checkpoint inhibitor treatment.

Randomized Trial of First-Line Tyrosine Kinase Inhibitor With or Without Radiotherapy for Synchronous Oligometastatic EGFR-Mutated Non-Small Cell Lung Cancer.

BACKGROUND: Adding radiotherapy (RT) to systemic therapy improves progression-free survival (PFS) and overall survival (OS) in oligometastatic non-small cell lung cancer (NSCLC). Whether these findings translate to epidermal growth factor receptor (EGFR)-mutated NSCLC remains unknown. The SINDAS trial (NCT02893332) evaluated first-line tyrosine kinase inhibitor (TKI) therapy for EGFR-mutated synchronous oligometastatic NSCLC and randomized to upfront RT vs no RT; we now report the prespecified interim analysis at 68% accrual. METHODS: Inclusion criteria were biopsy-proven EGFR-mutated adenocarcinoma (per amplification refractory mutation system or next generation sequencing), with synchronous (newly diagnosed, treatment naïve) oligometastatic (≤5 metastases; ≤2 lesions in any one organ) NSCLC without brain metastases. All patients received a first-generation TKI (gefitinib, erlotinib, or icotinib), and randomization was between no RT vs RT (25-40 Gy in 5 fractions depending on tumor size and location) to all metastases and the primary tumor/involved regional lymphatics. The primary endpoint (intention to treat) was PFS. Secondary endpoints included OS and toxicities. All statistical tests were 2-sided. RESULTS: A total of 133 patients (n = 65 TKI only, n = 68 TKI with RT) were enrolled (2016-2019). The median follow-up was 23.6 months. The respective median PFS was 12.5 months vs 20.2 months (P < .001), and the median OS was 17.4 months vs 25.5 months (P < .001) for TKI only vs TKI with RT. Treatment yielded no grade 5 events and a 6% rate of symptomatic grade 3-4 pneumonitis in the TKI with RT arm. Based on the efficacy results of this prespecified interim analysis, the ethics committee recommended premature cessation of this trial. CONCLUSIONS: As compared with a first-line TKI alone, addition of upfront local therapy using RT statistically significantly improved PFS and OS for EGFR-mutated NSCLC.

Tryptophan metabolism: Mechanism-oriented therapy for neurological and psychiatric disorders.

Neurological and psychiatric disorders are a category of chronic diseases that are widespread and pose serious mental and physical health problems for patients. The substrates, products, and enzymes of Tryptophan metabolism all contribute to the development of neurological and psychiatric disorders. This paper deals with three metabolic pathways of tryptophan that produce a series of metabolites called tryptophan Catabolics (TRYCATs). These metabolites are involved in pathological processes such as excitotoxicity, neuroinflammation, oxidative stress, and mitochondrial damage and are closely associated with neurological and psychiatric disorders such as Alzheimer's disease and depression. Here, we review the elements that affect how tryptophan metabolism is regulated, including inflammation and stress, exercise, vitamins, minerals, diet and gut microbes, glucocorticoids, and aging, as well as the downstream regulatory effects of tryptophan metabolism, including the regulation of glutamate (Glu), immunity, G-protein coupled receptor 35 (Gpr35), nicotinic acetylcholine receptor (nAChR), aryl hydrocarbon receptor (AhR), and dopamine (DA). In order to advance the general understanding of tryptophan metabolism in neurological and psychiatric disorders, this paper also summarizes the current situation and effective drugs of tryptophan metabolism in the treatment of neurological and psychiatric disorders and considers its future research prospects.

The impact of antibiotic selection and interval time among advanced non-small cell lung cancer patients receiving prior antibacterial treatment and first-line chemotherapy.

BACKGROUND: To determine whether antibiotic use before chemotherapy is associated with chemotherapy responses and patient outcomes among NSCLC patients and define the optimal interval between chemotherapy initiation and antibiotic treatment. MATERIALS AND METHODS: One thousand four hundred and four advanced NSCLC patients receiving first-line platinum-based doublets therapy were retrospectively analyzed. Kaplan-Meier curve evaluated the impact of antibiotic use and type of antibiotics on the survival of patients. The factors affect the patient's prognosis were further confirmed by Cox regression. The optimal interval between antibiotic treatment and the initiation of chemotherapy was determined by the X-tile program. RESULTS: NSCLC patients of 33.5% advanced underwent broad-spectrum antibiotic treatment prior to chemotherapy. In the chemotherapy only (Chemo) and chemotherapy plus antiangiogenesis (Chemo-angio) treatment groups, prior antibiotic treatment was associated with worse OS (Chemo: 13.8 vs. 17.6 months, p < 0.001; Chemo-angio:11.9 vs. 18.1 months, p = 0.012) and PFS (Chemo: 3.7 vs. 5.8 months, p < 0.001; Chemo-angio: 3.1 vs. 5.9 months, p < 0.001). Cox regression analysis revealed prior antibiotic administration as an independent predictor of OS and PFS (HR for PFS/OS: 1.925/1.452, both p < 0.001). Antibiotic usage duration (HR for PFS/OS: 1.030/1.036, p = 0.009/0.001) and type (PFS/OS: p < 0.001/p = 0.01) also showed significant association with patient prognosis, with calculated interval time cutoff values of 2, 4, and 2 days for fluoroquinolones, ß-lactamase inhibitors, and cephalosporins, respectively. CONCLUSION: Antibiotic use before first-line chemotherapy was associated with poor results in advanced NSCLC patients; treatment length and type being strongly correlated with patient outcomes. Appropriate prolongation of the time between two treatments may enhance patient survival. Further prospective research is however necessary.

Early effect of extracorporeal membrane oxygenation and factors related to early outcome in adult patients with fulminant myocarditis / 中华心血管病杂志

Objective: To evaluate the efficacy within the first 24 h post extracorporeal membrane pulmonary oxygenation (ECMO) and the impact of early efficacy on the prognosis of adult patients with fulminant myocarditis (FM). Methods: This retrospective case analysis study included hospitalized patients (age≥18 years) who were diagnosed with fulminant myocarditis from November 2016 to May 2021 in the First Affiliated Hospital of Zhengzhou University. Patients were divided into survival or non-survival groups according to treatment outcomes. The age, sex, treatments, drug use, ECMO use, clinical and laboratory data (before and 24 h after the use of ECMO) were analyzed. The change rate of clinical and laboratory data after 24 h use of ECMO was calculated to find differences between two groups. Multivariate logistic regression was used to analyze the related factors with in-hospital death and complication between the two groups. Results: A total of 38 FM patients treated with ECMO were included. There were 23 cases (60.5%) in the survival group, aged (39.6±13.7) years, and 17 (73.9%) cases were female. The total ECMO time was (134.4±71.3)h. There were 15 cases (39.5%) in non-survival group, aged (40.0±15.8) years, and there were 12(80.0%) female, the ECMO time was (120.1±72.4) h in this group. The proportion of tracheal intubation and continuous renal replacement therapy in the survivor group and dosage of norepinephrine within 24 h after ECMO implantation were significantly less than in non-survival group (all P<0.05). There was no significant difference in all efficacy related biochemical indexes between two groups before ECMO use. The levels of lactic acid, procalcitonin, creatinine, alanine aminotransferase, aspartate aminotransferase, creatine kinase-MB, cardiac troponin I and N-terminal B-type natriuretic peptide prosoma were significantly less in survival group than in non-survival group at 24 h after the use of ECMO (all P<0.05). Results of multivariate logistic regression analysis showed that the higher 24 h change rate of creatinine (OR=0.587, 95%CI 0.349-0.986, P=0.044) and creatine kinase-MB (OR=0.177, 95%CI 0.037-0.841, P=0.029) were positively correlated with reduced risk of in-hospital mortality. The central hemorrhage and acute kidney injury in survival group were less than in non-survivor group (P<0.05). Conclusions: After 24 h early use of ECMO in FM patients, the improvement of various efficacy related biochemical test indexes in the survival group was better than that in the non-survival group. Faster reduction of creatine kinase-MB and creatinine values within 24 h ECMO use is positively correlated with reduced risk of in-hospital mortality in adult patients with FM.

Smart Design of Mitochondria-Targeted and ROS-Responsive CPI-613 Delivery Nanoplatform for Bioenergetic Pancreatic Cancer Therapy.

Mitochondria, as the powerhouse of most cells, are not only responsible for the generation of adenosine triphosphate (ATP) but also play a decisive role in the regulation of apoptotic cell death, especially of cancer cells. Safe potential delivery systems which can achieve organelle-targeted therapy are urgently required. In this study, for effective pancreatic cancer therapy, a novel mitochondria-targeted and ROS-triggered drug delivery nanoplatform was developed from the TPP-TK-CPI-613 (TTCI) prodrug, in which the ROS-cleave thioketal functions as a linker connecting mitochondrial targeting ligand TPP and anti-mitochondrial metabolism agent CPI-613. DSPE-PEG2000 was added as an assistant component to increase accumulation in the tumor via the EPR effect. This new nanoplatform showed effective mitochondrial targeting, ROS-cleaving capability, and robust therapeutic performances. With active mitochondrial targeting, the formulated nanoparticles (TTCI NPs) demonstrate much higher accumulation in mitochondria, facilitating the targeted delivery of CPI-613 to its acting site. The results of in vitro antitumor activity and cell apoptosis revealed that the IC50 values of TTCI NPs in three types of pancreatic cancer cells were around 20~30 µM, which was far lower than those of CPI-613 (200 µM); 50 µM TTCI NPs showed an increase in apoptosis of up to 97.3% in BxPC3 cells. Therefore, this mitochondria-targeted prodrug nanoparticle platform provides a potential strategy for developing safe, targeting and efficient drug delivery systems for pancreatic cancer therapy.

Development and validation of a nomogram for assessing survival in extensive-stage small-cell lung cancer patients with superior vena cava syndrome referred for thoracic radiotherapy: a comparison of upfront vs. consolidative approaches.

PURPOSE: This study sought to design and validate a nomogram capable of predicting outcomes in extensive-stage small-cell lung cancer (ES-SCLC) patients with superior vena cava syndrome (SVCS) based upon the timing of their radiotherapy treatment. METHODS: We retrospectively analyzed data from 175 ES-SCLC patients with SCVS, comparing outcomes between those that underwent upfront thoracic radiotherapy (initial radiotherapy with simultaneous chemotherapy) and those that underwent consolidative thoracic radiotherapy (following 4-6 cycles of chemotherapy). Significant predictors of patient outcomes were identified using a Cox proportional hazard model and were used to construct our nomogram. This model was subsequently validated using receiver operating characteristic (ROC) curves, concordance index (C-index) values, and a risk classification system in order to evaluate its discriminative and predictive accuracy. RESULTS: The overall survival (OS) of ES-SCLC patients with SVCS that underwent chemotherapy (CT), consolidative thoracic radiotherapy (cc-TRT), and upfront thoracic radiotherapy (cu-TRT) was 8.2, 11.7, and 14.9 months, respectively (p < 0.001), with respective progression-free survival (PFS) durations of 3.3, 5.0, and 7.3 months (p < 0.001). A multivariate regression analysis revealed age, gender, ECOG performance status, sites of tumor metastasis, and treatment approach to all be independent predictors of survival outcomes. A nomogram was therefore developed incorporating these factors. C­index values upon internal and external validation of this nomogram were 0.7625 and 0.7959, respectively, and ROC and calibration curves revealed this model to be accurate and consistent. CONCLUSIONS: We found that upfront thoracic radiotherapy in combination with chemotherapy may be associated with a positive impact on outcomes in ES-SCLC patients with SVCS.

Stavudine exposure results in developmental abnormalities by causing DNA damage, inhibiting cell proliferation and inducing apoptosis in mouse embryos.

Stavudine is an anti-AIDS drug widely used to prevent HIV transmission from pregnant mothers to the fetuses in underdeveloped countries for its low price. However, there is still a controversy on whether stavudine affects embryo development. In the current study, embryotoxicity of stavudine was evaluated using cultured mouse embryos with the concentrations: 5, 10, 15 µM and vehicle control. The data indicated that the effect of stavudine was dose-dependent at early neurogenesis. Stavudine exposure reduced somite numbers, yolk sac diameter, crown-rump length, and increased the rate of embryonic degeneration compared with the control. We chose the lowest but clearly toxic concentration: 5 µM to investigate the molecular mechanisms of the damage. At the molecular level, stavudine produced DNA damage, increased the levels of the phospho-CHK1 and cleaved-caspase-3, and decreased the expression level of proliferating cell nuclear antigen. These changes indicated that stavudine caused a coordinated DNA damage response, inhibited cell proliferation, and induced apoptosis in the embryos. Collectively these results suggest that stavudine exposure disturbs the embryonic development, and its use in pregnant mothers should be re-examined.

The anticancer effects of Cucurbitacin I inhibited cell growth of human non­small cell lung cancer through PI3K/AKT/p70S6K pathway.

The present study aimed to identify potential anticancer effects of Cucurbitacin I regulators on cell growth of human non­small cell lung cancer (NSCLC) and to explore their mechanism. The results indicated that the anticancer effects of Cucurbitacin I markedly attenuated cell proliferation, and induced apoptosis in NSCLC. Furthermore, Cucurbitacin I suppressed phosphatidylinositol­4,5­bisphosphate 3­kinase (PI3K), phosphorylation (p)­AKT and p­p70S6K pathway in NSCLC. Then, (PI3K) inhibitor increased anticancer effects of Cucurbitacin I on NSCLC. In conclusion, the present results indicated that Cucurbitacin I inhibited cell growth of human NSCLC through PI3K/AKT/p70S6K signaling pathway.

Apatinib alone or combined with radiotherapy in metastatic prostate cancer: Results from a pilot, multicenter study.

BACKGROUND: To study safety and efficacy of apatinib in combination of radiotherapy in patients with symptomatic bony disease prostate cancer(SBPC), based on the potential synergistic antitumor activity between apatinib and Radiation Therapy (RT). PATIENTS AND METHODS: In phase I dose escalation part, 18 patients received apatinib dose at 250 mg every other day, 250 mg daily and 500 mg daily. In phase II part, the 250 mg daily cohorts were expanded to 20 patients in combination of RT (6 Gy/fraction, 5 fraction in total), one patient lost followed up and excluded the study, comparing with RT alone cohort with 10 patients, ratio of RT to RT + apatinib was 1 to 2. Evaluations included adverse events (AEs), prostate specific antigen (PSA) changes, radiographic evaluation and pain relief. RESULTS: In phase I study, common apatinib-related AEs (arAEs) were fatigue, anorexia, hand foot syndrome, proteinuria, and hypertension (HTN). Grade 3arAEs included HTN, proteinuria, liver dysfunction. In phase II study, combination apatinib with RT cohorts, AEs events increased comparing with either apatinib alone or RT alone; at the same time, combination cohorts showed PSA declines of ≥50% in 12 patients, and stable disease in 6 patients. Combination cohorts had pain control significantly improved in both level and duration comparing with RT alone. CONCLUSIONS: In SBPC patients, apatinib at less than 500 mg daily dose as mono-therapy had tolerable toxicity. Apatinib at dose of 250 mg daily in combining with RT synergized pain control, the overall AEs were manageable. Further studies are needed in large sample size future trials.

DNA repair gene polymorphisms and clinical outcome of patients with primary small cell carcinoma of the esophagus.

Polymorphisms in DNA repair genes impact on the synthesis of DNA repair proteins that are crucial to the repair of DNA damages induced by chemotherapy and radiotherapy. We retrospectively examined whether there was an association between the selected six single nucleotide polymorphisms (SNPs) of five DNA repair genes (PARP1-Val762Ala, XRCC1-Arg194Trp, XRCC1-Arg399Gln, XPC-Lys939Gln, BRCA1-Lys1183Arg, and BRCA2-Asn372His) and the clinical outcome of patients with primary small cell carcinoma of esophagus (SCCE), and it showed that the median progression-free survival (PFS) and the overall survival (OS) were 11.8 versus 9.7 months (P = 0.041) and 17.4 versus 14.8 months (P = 0.032) for patients carrying the variant allele (T/C + C/C) and the wild-type allele (T/T) of PARP1-Val762Ala polymorphism, respectively. However, no statistical significance was observed in the other five polymorphic loci (P > 0.05). When these six SNPs were combined, however, patients with at least three variant genotypes had significantly longer PFS and OS compared with those carrying less than three variant genotypes (P = 0.009 and P = 0.007, respectively). The presence of at least three polymorphic variants in certain DNA repair genes may impact on patient survival and could be a potential genomic predictor of clinical response to DNA-damaging treatment in SCCE patients.

[Case classification in measles surveillance system under the Two-level Logistic Model].

OBJECTIVE: To study the prevalence rates of Rash and Febrile Illnesses (RFIs) including measles, rubella, scarlet fever, exanthema subitum and the differences among measles and other RFIs to tentatively formulate the logistic regression model through clinical manifestation. METHODS: All the suspected cases of measles, rubella, scarlet fever, exanthema subitum reported by the county/prefecture lever hospitals at four counties were collected during March 2011 to February 2012. When setting laboratory confirmed measles as dependent variable and existed symptoms as independent variable, a logistic regression model was formulated and optimal operational point (OOP)chosen, according to the ROC curve. RESULTS: A total number of 551 cases were collected but the consistency of measles diagnosis between clinical and laboratory was not satisfied, with Kappa value = 0.349, same to the diagnosis of rubella. As for the result from the two-lever logistic regression model, symptoms that related to the confirmation of measles would include cough (OR = 5.75), conjunctivitis (OR = 3.00), Koplik spot (OR = 7.52), lymphadenectasis(OR = 0.07), rash after fever (OR = 0.07). The area under ROC curve was 0.97 and the optimal operational point was 0.249. CONCLUSION: A logistic regression model was formulated using the clinical symptoms which was resulted in better performance on prediction. As the sample size of this survey was small, the expansion on the scale of investigation and laboratory testings were needed before the types and components of measles-related RFIs be clarified.

Discerning primary tumors from metastases in synchronous nasopharyngeal squamous cell carcinoma and cutaneous squamous cell carcinoma: A case report and review of the literature.

Nasopharyngeal carcinoma is one of the most common types of malignant tumor in Southern China and Southeast Asia, and its etiology is closely associated with Epstein-Barr virus (EBV) infection. Non-keratinizing carcinoma accounts for >95% of all nasopharyngeal carcinoma cases. In addition, metastatic nasopharyngeal carcinoma from other locations in the body is extremely rare. This study reports the case of a 53-year-old female who presented with a lesion on the left nasal alar skin that had slowly developed over a five-year period. A biopsy was obtained and the lesion was histologically diagnosed as cutaneous squamous cell carcinoma (SCC). A nasopharyngeal neoplasm was also detected by 18-fluorine-2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography and nasopharyngoscopy. A biopsy of the nasopharyngeal neoplasm confirmed a diagnosis of SCC. However, a small EBV-encoded nuclear RNA (EBER) test demonstrated that the nasopharyngeal tumor cells were all negative for EBV. As the majority of nasopharyngeal carcinomas were positive for EBER, it was concluded that the nasopharyngeal carcinoma had metastasized from the cutaneous SCC. A brief review of literature is also presented, in addition to a discussion of the pathogen, epidemiology and diagnosis of cutaneous and nasopharyngeal carcinomas.

Quercetin liposomes protect against radiation-induced pulmonary injury in a murine model.

In the present study, the hypothesis that quercetin liposomes are able to effectively protect against radiation-induced pulmonary injury in a murine model was tested. C57BL/6J mice receiving whole-thorax radiotherapy (16 Gy) were randomly divided into three groups: control, radiation therapy plus saline (RT+NS) and RT plus quercetin (RT+QU). At 1, 4, 8 and 24 weeks post-irradiation, lung injury was assessed by measuring oxidative damage and the extent of acute pneumonitis and late fibrosis. In the lung tissues from the RT+NS group, the malondialdehyde (MDA) levels were significantly elevated and superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities were significantly reduced; the total cell counts and inflammatory cell proportions in the bronchoalveolar lavage fluid (BALF), plasma tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-ß1 concentrations and the hydroxyproline (HP) content were significantly increased. Quercetin liposome administration significantly reduced the MDA content and increased SOD and GSH-PX activities in the lung tissues, and reduced the total cell counts and inflammatory cell proportions in the BALF, plasma TNF-α and TGF-ß1 concentrations and the HP content in the lung tissues. A histological examination revealed suppression of the inflammatory response and reduced TGF-ß1 expression and fibrosis scores. Radiation-induced oxidative damage ranged from pneumonitis to lung fibrosis. Quercetin liposomes were shown to protect against radiation-induced acute pneumonitis and late fibrosis, potentially by reducing oxidative damage.

Synchronous nasopharyngeal carcinoma and cardia adenocarcinoma accompanied with suspected dermatomyositis: A case report and literature review.

Synchronous multiple primary cancers are relatively uncommon and synchronous multiple cancers in coexistence with dermatomyositis (DM) are extremely rare. In the present study, we report a case of a 64-year-old male with nasopharyngeal undifferentiated non-keratinizing carcinoma and cardia adenocarcinoma which were diagnosed synchronously. In addition, suspected DM was diagnosed during the course of chemotherapy. The symptoms of DM were exaggerated even when methylprednisolone while administered. The patient succumbed to nutritional deterioration four months following his initial admission. In the present study, the etiologies of multiple primary cancers are discussed and a brief review of the literature on the correlation between malignance and DM was conducted.