Suspension Cell Culture of Polyscias fruticosa (L.) Harms in Bubble-Type Bioreactors-Growth Characteristics, Triterpene Glycosides Accumulation and Biological Activity.

Polyscias fruticosa (L.) Harms, or Ming aralia, is a medicinal plant of the Araliaceae family, which is highly valued for its antitoxic, anti-inflammatory, analgesic, antibacterial, anti-asthmatic, adaptogenic, and other properties. The plant can be potentially used to treat diabetes and its complications, ischemic brain damage, and Parkinson's disease. Triterpene glycosides of the oleanane type, such as 3-O-[ß-D-glucopyranosyl-(1→4)-ß-D-glucuronopyranosyl] oleanolic acid 28-O-ß-D-glucopyranosyl ester (PFS), ladyginoside A, and polysciosides A-H, are mainly responsible for biological activities of this species. In this study, cultivation of the cell suspension of P. fruticosa in 20 L bubble-type bioreactors was attempted as a sustainable method for cell biomass production of this valuable species and an alternative to overexploitation of wild plant resources. Cell suspension cultivated in bioreactors under a semi-continuous regime demonstrated satisfactory growth with a specific growth rate of 0.11 day-1, productivity of 0.32 g (L · day)-1, and an economic coefficient of 0.16 but slightly lower maximum biomass accumulation (~6.8 g L-1) compared to flask culture (~8.2 g L-1). Triterpene glycosides PFS (0.91 mg gDW-1) and ladyginoside A (0.77 mg gDW-1) were detected in bioreactor-produced cell biomass in higher concentrations compared to cells grown in flasks (0.50 and 0.22 mg gDW-1, respectively). In antibacterial tests, the minimum inhibitory concentrations (MICs) of cell biomass extracts against the most common pathogens Staphylococcus aureus, methicillin-resistant strain MRSA, Pseudomonas aeruginosa, and Escherichia coli varied within 250-2000 µg mL-1 which was higher compared to extracts of greenhouse plant leaves (MIC = 4000 µg mL-1). Cell biomass extracts also exhibited antioxidant activity, as confirmed by DPPH and TEAC assays. Our results suggest that bioreactor cultivation of P. fruticosa suspension cell culture may be a perspective method for the sustainable biomass production of this species.

Utility of adjuvant radioactive iodine therapy after reoperation in papillary thyroid carcinoma with cervical lymph node recurrence.

PURPOSE: The aim of this study was to evaluate the utility of RAI therapy after reoperation for patients with LN relapse. MATERIALS AND METHODS: We retrospectively evaluated PTC patients who had undergone reoperation due to cervical LN recurrence. We used the chi-square test, Fisher's exact test, Student's t test and the Mann-Whitney U test to compare characteristics between patients retreated with RAI and those who did not receive RAI after reoperation. A multivariate logistic regression model was used to determine the association between RAI and biochemical response. By means of the Kaplan-Meier estimator and a multivariate Cox proportional hazard model, we assessed whether administration of RAI after reoperation is associated with improved prognosis. RESULTS: RAI therapy was closely associated with a superior biochemical response in all selected patients according to both univariate (p = 0.012) and multivariate analyses (p = 0.020). Thirteen of 97 patients developed a second recurrence or progression of structural disease during follow-up. A Kaplan-Meier progression-free survival (PFS) curve showed that high post-retreatment thyroglobulin (Tg) levels (≥ 1 ng/mL) were associated with unfavourable prognosis (p = 0.0172). In the subgroup analysis, univariate analysis revealed that only patients without extranodal invasion who received adjuvant RAI therapy achieved better PFS than those who did not receive RAI therapy (p = 0.0203). Multivariate analysis showed that RAI (p = 0.045) also improved PFS in patients without extranodal invasion. CONCLUSIONS: Adjuvant RAI after reoperation for PTC recurrence/persistence was associated with a favourable biochemical response and tended to increase PFS. Specifically, it was significantly associated with improved PFS only in patients without extranodal extension.

Sorafenib as first-line treatment for patients with primary hepatocellular carcinoma: an outcome evaluation.

OBJECTIVE: To evaluate the clinical outcomes following first-line treatment with sorafenib in patients with primary hepatocellular carcinoma (HCC). METHODS: This retrospective cohort study enrolled patients with primary HCC that had been treated with sorafenib. Their data were collected from the hospital medical records database at three time-points: after three cycles, after six cycles and at the end of the sorafenib treatment regimen. The starting dose was 800 mg/day sorafenib but this could be reduced to 600 mg/day or 400 mg/day if patients developed adverse events (AEs). RESULTS: A total of 98 patients participated in the study. Of these, nine (9.2%) had a partial response, 47 patients (48.0%) had stable disease and 42 patients (42.9%) had progressive disease. The overall disease control rate was 57.1% (56 of 98 patients). Median progression-free survival for the overall cohort was 4.7 months. The most common AEs were hand-foot skin reaction (49 of 98 patients; 50.0%), fatigue (41 of 98 patients; 41.8%), appetite loss (39 of 98 patients; 39.8%) and hepatotoxicity/transaminitis (24 of 98 patients; 24.5%). The majority of the AEs were toxicity grades 1 and 2. CONCLUSION: Sorafenib as a first-line treatment for primary HCC patients provided survival benefits and the AEs were well tolerated by patients.

Assessment of Functional and Physical Performances of Pre-filled Syringes in Deep Cold Storage Conditions.

The recent emergence of new drug technologies such as messenger ribonucleic acid-based vaccines developed to fight the outbreak of the COVID-19 global pandemic has driven increased demand for delivery solutions capable of withstanding deep cold storage conditions down to -50°C, and even down to -80°C. Although significant data exist for deep cold storage in vials, little evidence is available for pre-filled syringes. Because pre-filled syringes serve as both the storage container and the delivery mechanism, there are additional risks to performance that must be evaluated, such as plunger gliding performance, syringe lubrication, silicone layer stability, and container closure integrity (CCI). In the present study, a comprehensive assessment of functional and physical performances of pre-filled syringes (PFS filled with water) was performed after one or multiple freeze/thaw (F/T) cycles between ambient temperature and various temperature cycles including -40°C, -50°C or -80°C for both 'staked needle' and 'luer lock' configurations. The experiments were guided by historical normative methods such as ISO 11040-4 and USP <1207> and combined with headspace gas analysis for barrel-stopper tightness testing. In addition, they were complemented with a novel approach, namely in situ real-time optical imagery, to track plunger stopper movement during the F/T cycle. The findings indicated that there is no significant impact on the functional performances from F/T down to -80°C, whereas no CCI risk was found after F/T down to -50°C.

Ovarian clear cell carcinoma with or without endometriosis origin in a single institution cohort.

BACKGROUND: As ovarian clear cell carcinoma (OCCC) has distinct clinical features, biology, genetic characteristics and mechanisms of pathogenesis, and whether the origin of endometriosis or not affects the prognosis of OCCC remains controversial. METHODS: We retrospectively collected medical records and follow-up data of patients with OCCC treated at the Obstetrics and Gynecology Hospital of Fudan University from January 2009 to December 2019. Further, we divided patients into 2 groups. Group 1: non-endometriosis origin; Group 2: endometriosis origin. Clinicopathological characteristics and survival outcomes were compared between the 2 groups. RESULTS: A total of one hundred and twenty-five patients with ovarian clear cell carcinoma were identified and included. In the overall patients' population, the 5 year overall survival was 84.8%, the mean overall survival was 85.9 months. The results of the stratified analysis showed that early stage (FIGO stage I/II) OCCC had a good prognosis. The results of univariate analyses indicated that a statistically significant relationship between overall survival (OS) and FIGO stage, lymph node metastasis, peritoneum metastasis, chemotherapy administration methods, Chinese herbal treatment, molecular target therapy. As for progression-free survival (PFS), a significant relationship between PFS and child-bearing history, largest residual tumor size, FIGO stage, tumor maximum diameter, lymph node metastasis was found, respectively. FIGO stage and lymph node metastasis are common poor prognostic factors affecting OS and PFS. The multivariate regression analysis revealed that FIGO stage (p = 0.028; HR, 1.944; 95% CI 1.073-3.52) and treatment by Chinese herbs (p = 0.018; HR, 0.141; 95% CI 0.028-0.716) were identified as influencing factors with regard to survival. The presence or absence of lymphadenectomy did not affect OS of 125 OCCC patients (p = 0.851; HR, 0.825; 95% CI 0.111-6.153). There was a trend towards a better prognosis for patients with OCCC of endometriosis origin than those with OCCC of non-endometriosis origin (p = 0.062; HR, 0.432; 95% CI 0.179-1.045). The two groups differed with respect to several clinicopathological factors. And the proportion of patients with disease relapse was higher in Group 1 (46.9%) than in Group 2 (25.0%), with a statistically significant difference (p = 0.048). CONCLUSIONS: Surgical staging and treatment by Chinese herbs postoperatively are two independent prognostic factors affecting the OS of OCCC, early detection and Chinese herbal medicine combined with chemotherapy postoperatively may be a good choice. Tumor with endometriosis-origin was found less likely to relapse. While the non-necessity of lymphadenectomy in advanced ovarian cancer has been proven, the need for lymphadenectomy in the early stage ovarian cancer, including early stage OCCC, still deserved to be explored.

Low absolute CD4+ T cell counts in peripheral blood: an independent predictor of inferior survival in natural killer/T-cell lymphoma-a retrospective cohort study.

Background: Lymphopenia at diagnosis is considered a negative prognostic factor for patients with extra-nodal natural killer (NK)/T-cell lymphoma (ENKTL), especially that of the absolute cluster of differentiation 4+ T cell count (ACD4C), which has previously been identified as an independent prognostic factor in other hematologic malignancies. However, there is limited data available regarding the prognostic value of peripheral blood T lymphocyte subsets in ENKTL patients. The purpose of this study was to investigate the prognostic value of lymphocyte subsets, especially the ACD4C in ENKTL as a clinical biomarker. Methods: We analyzed the clinical data of 176 patients who met the inclusion criteria in Cancer Center of Integrated Hospital of Traditional Chinese Medicine, Southern Medical University from 2000 to 2018, including baseline clinical factors and ACD4C detected by flow cytometry, and examined the correlation between the results and clinical parameters and long-term outcomes. Results: The complete response rate of the high ACD4C group was 57.6%, which was significantly higher than that of the low ACD4C group (15.1%, P<0.001). The univariate analysis results showed that at a median follow-up time of 58.2 months, patients with a high ACD4C had significantly superior progression-free survival (PFS) and overall survival (OS) (P=0.034 and P=0.001, respectively). The multivariate analysis results revealed that Eastern Cooperative Oncology Group performance status (ECOG PS) and the ACD4C were independent prognostic factors for OS [RR (95% CI): 2.288 (1.209-4.328), P=0.011 and RR (95% CI): 2.058 (1.070-3.968), P=0.031, respectively]. ECOG PS was also an independent prognostic factor for PFS [RR (95% CI): 1.858 (1.064-3.244), P=0.029], while ACD4C tended to be independently correlated with PFS (P=0.085). Conclusions: In this large cohort study, we found that the ACD4C was associated with survival outcomes in ENKTL patients. It is a potential biomarker, which may potentially be applied to clinical.

Establishment of a Nomogram-Based Prognostic Model (LASSO-COX Regression) for Predicting Progression-Free Survival of Primary Non-Small Cell Lung Cancer Patients Treated with Adjuvant Chinese Herbal Medicines Therapy: A Retrospective Study of Case Series.

Nowadays, Jin-Fu-Kang oral liquid (JFK), one of Chinese herbal medicines (CHMs) preparations, has been widely used as an adjuvant therapy for primary non-small cell lung cancer (PNSCLC) patients with the syndrome of deficiency of both Qi and Yin (Qi-Yin deficiency pattern) based on Traditional Chinese Medicine (TCM) theory. However, we found insufficient evidence of how long-term CHM treatment influence PNSCLC patients' progression-free survival (PFS). Thus, using electronic medical records, we established a nomograph-based prognostic model for predicting PNSCLC patients' PFS involved with JFK supplementary formulas (JFK-SFs) over 6 months, in order to preliminarily investigate potential predictors highly related to adjuvant CHMs therapies in theoretical epidemiology. In our retrospective study, a series of 197 PNSCLC cases from Long Hua Hospital were enrolled by non-probability sampling and divided into 2 datasets at the ratio of 5:4 by Kennard-Stone algorithm, as a result of 109 in training dataset and 88 in validation dataset. Besides, TNM stage, operation history, sIL-2R, and CA724 were considered as 4 highly correlated predictors for modeling based on LASSO-Cox regression. Additionally, we respectively used training dataset and validation dataset for establishment including internal validation and external validation, and the prediction performance of model was measured by concordance index (C-index), integrated discrimination improvement, and net reclassification indices (NRI). Moreover, we found that the model containing clinical characteristics and bio-features presented the best performance by pairwise comparison. Next, the result of sensitivity analysis proved its stability. Then, for preliminarily examination of its discriminative power, all eligible cases were divided into high-risk or low-risk progression by the cut-off value of 57, in the light of predicted nomogram scores. Ultimately, a completed TRIPOD checklist was used for self-assessment of normativity and integrity in modeling. In conclusion, our model might offer crude probability of uncertainly individualized PFS with long-term CHMs therapy in the real-world setting, which could discern the individuals implicated with worse prognosis from the better ones. Nevertheless, our findings were prone to unmeasured bias caused by confounding factors, owing to retrospective cases series.

The Canonical Table of the Genetic Code as a periodic system of triplets.

The Canonical Table of the Genetic Code (CTGC) is constructed theoretically on the basis of the similarity of PFs (PF) of proteins with the conformation of 4-arc chain graphs (Karasev, 2019). Of the 64 conformations of the graph, specified by the position of the connectivity edges, and the matrices of 6 variables (x1 … x6), xi = (0, 1), 4 blocks of 16 elements each were formed. Then they were coded in the form of triplets based on the correspondence of pairs of variables to four letters of the code: 00 = C, 01 = U, 10 = G, 11 = A, and supplemented based on the known triplet-amino acid assignment. The resulting table is compared with the Periodic Table of Chemical Elements (PTCE). As in the PTCE, this CTGC has an initial element - a triplet that encodes graphs with zero number of connected edges. Within each block, vacancies are filled with connectivity edges in two alternative ways, both in rows and in the columns. As we move from the initial block 00 to the final block 11, there is a sequential filling of vacancies for variables x3x4: 00, 01, 10, 11. In general, the CTGC can be considered as a periodic system of triplets. Comparison with the previously described variety of tables of the genetic code made it possible to conclude that the CTGC more adequately reflects the properties of the genetic code. Prospects for the possible application of this table are being discussed.

Early outcomes of high-dose-rate brachytherapy combined with ultra-hypofractionated radiation in higher-risk prostate cancer.

PURPOSE: This study evaluated outcomes associated with a high-dose-rate (HDR) brachytherapy boost combined with stereotactic body radiation therapy (SBRT) for patients with higher-risk localized prostate cancer. MATERIALS AND METHODS: We identified 101 patients with National Comprehensive Cancer Network high-risk, unfavorable intermediate-risk, or favorable intermediate-risk with probable extra-prostatic extension treated with HDR brachytherapy (15 Gy x 1 fraction) followed by SBRT (5 Gy x 5 daily fractions to the prostate and/or seminal vesicles and/or pelvic lymph nodes). Androgen deprivation therapy was used in 55.4% of all patients (90% of high-risk, 33% of intermediate-risk). Toxicities according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0 and International Prostate Symptom Scores were prospectively documented at each followup visit. Biochemical relapse was defined as PSA nadir +2ng/mL. RESULTS: The median follow-up time after SBRT was 24.1 months. No grade ≥3 toxicities were observed. The incidence of acute and late grade 2 gastrointestinal toxicities was both 0.99%. Acute and late grade 2 genitourinary (GU) toxicities were observed in 5.9% and 9.9%, respectively. Median time to a grade 2 GU toxicity was 6 months with a 14% 2-year actuarial rate of grade 2 GU toxicity. Median International Prostate Symptom Scores at 24 months was not significantly different than baseline (6 vs. 5; p = 0.24). Inclusion of pelvic lymph nodes and absence of a rectal spacer were significantly associated with more frequent grade ≥1 GU toxicity, but not grade ≥2 GU or gastrointestinal toxicity. The 2-year biochemical relapse free survival was 97%. CONCLUSIONS: HDR brachytherapy combined with SBRT was associated with a favorable early toxicity profile and encouraging cancer control outcomes.

The JPJDF has Synergistic Effect with Fluoropyrimidine in the Maintenance Therapy for Metastatic Colorectal Cancer.

BACKGROUND: Maintenance chemotherapeutic regimen with low toxicity is needed for metastatic colorectal cancer. A recent patent has been issued on the spleen-strengthening and detoxification prescription (JPJDF), a traditional Chinese herbal medicinal formula with anti-angiogenesis effect. The clinical effect of JPJDF on the maintenance treatment of advanced colorectal cancer has not been evaluated. OBJECTIVE: This study aims to evaluate the effectiveness and safety of JPJDF in combination with fluoropyrimidine compared to fluoropyrimidine alone as maintenance therapy for metastatic colorectal cancer. METHODS: We applied a prospective, randomized, double-blinded, single center clinical study design. A total of 137 patients with advanced colorectal cancer were recruited. Patients received either Fluoropyrimidine (Flu-treated group, n = 68), or Fluoropyrimidine plus JPJDF (Flu-F-treated group, n = 69) as maintenance treatment after 6-cycle of FOLFOX4 or FOLFORI induction treatment. The primary endpoints were Progression-Free Survival (PFS) and Overall Survival (OS). The secondary endpoints were safety, Performance Status (PS) score and other symptoms. RESULTS: The endpoint of disease progression was observed in 91.7% of patients. The PFS was 5.0 months and 3.0 months in the Flu-F-treated and Flu-treated groups, respectively. The OS was 15.0 months and 9.0 months in the Flu-F-treated and Flu-treated groups, respectively. Some common symptoms, such as hypodynamia, anepithymia, dizziness and tinnitus and shortness of breath, were improved in the Flu-F-treated group. There was no significant difference in the common adverse reactions between the two groups. CONCLUSION: JPJDF and fluoropyrimidine have synergistic effect in the maintenance treatment of mCRC.

Sunitinib Versus Sorafenib as Initial Targeted Therapy for mCC-RCC With Favorable/Intermediate Risk: Multicenter Randomized Trial CROSS-J-RCC.

PURPOSE: The present study compared the efficacy of sunitinib and sorafenib as first-line treatment of metastatic clear cell renal cell carcinoma (mCC-RCC) with favorable or intermediate Memorial Sloan Kettering Cancer Center (MSKCC) risk. PATIENTS AND METHODS: Treatment-naive patients with mCC-RCC were randomized to receive open-label sunitinib followed by sorafenib (SU/SO) or sorafenib followed by sunitinib (SO/SU). The primary endpoint was first-line progression-free survival (PFS). The secondary endpoints were total PFS and overall survival (OS). RESULTS: Of the 124 patients enrolled at 39 institutions from February 2010 to July 2012, 120 were evaluated. The median first-line PFS duration was 8.7 and 7.0 months in the SU/SO and SO/SU groups, respectively (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.42-1.08). The total PFS and OS were not significantly different between the SU/SO and SO/SU groups (27.8 and 22.6 months; HR, 0.73; 95% CI, 0.428-1.246; and 38.4 and 30.9 months; HR, 0.934; 95% CI, 0.588-1.485, respectively). The subgroup analysis revealed that the total PFS with SU/SO was superior to the total PFS with SO/SU in the patients with favorable MSKCC risk and those with < 5 metastatic sites). SO/SU was superior to SU/SO for patients without previous nephrectomy. CONCLUSIONS: No statistically significant differences were found in first-line PFS, total PFS, or OS between the 2 treatment arms (ClinicalTrials.gov identifier, NCT01481870).

A comparison of spinal laser interstitial thermotherapy with open surgery for metastatic thoracic epidural spinal cord compression.

OBJECTIVE: The proximity of the spinal cord to compressive metastatic lesions limits radiosurgical dosing. Open surgery is used to create safe margins around the spinal cord prior to spinal stereotactic radiosurgery (SSRS) but carries the risk of potential surgical morbidity and interruption of systemic oncological treatment. Spinal laser interstitial thermotherapy (SLITT) in conjunction with SSRS provides local control with less morbidity and a shorter interval to resume systemic treatment. The authors present a comparison between SLITT and open surgery in patients with metastatic thoracic epidural spinal cord compression to determine the advantages and disadvantages of each method. METHODS: This is a matched-group design study comprising patients from a single institution with metastatic thoracic epidural spinal cord compression that was treated either with SLITT or open surgery. The two cohorts defined by the surgical treatment comprised patients with epidural spinal cord compression (ESCC) scores of 1c or higher and were deemed suitable for either treatment. Demographics, pre- and postoperative ESCC scores, histology, morbidity, hospital length of stay (LOS), complications, time to radiotherapy, time to resume systemic therapy, progression-free survival (PFS), and overall survival (OS) were compared between groups. RESULTS: Eighty patients were included in this analysis, 40 in each group. Patients were treated between January 2010 and December 2016. There was no significant difference in demographics or clinical characteristics between the cohorts. The SLITT cohort had a smaller postoperative decrease in the extent of ESCC but a lower estimated blood loss (117 vs 1331 ml, p < 0.001), shorter LOS (3.4 vs 9 days, p < 0.001), lower overall complication rate (5% vs 35%, p = 0.003), fewer days until radiotherapy or SSRS (7.8 vs 35.9, p < 0.001), and systemic treatment (24.7 vs 59 days, p = 0.015). PFS and OS were similar between groups (p = 0.510 and p = 0.868, respectively). CONCLUSIONS: The authors' results have shown that SLITT plus XRT is not inferior to open decompression surgery plus XRT in regard to local control, with a lower rate of complications and faster resumption of oncological treatment. A prospective randomized controlled study is needed to compare SLITT with open decompressive surgery for ESCC.

Metastatic bone disease: Pathogenesis and therapeutic options: Up-date on bone metastasis management.

Bone metastases (BM) are a common complication of cancer, whose management often requires a multidisciplinary approach. Despite the recent therapeutic advances, patients with BM may still experience skeletal-related events and symptomatic skeletal events, with detrimental impact on quality of life and survival. A deeper knowledge of the mechanisms underlying the onset of lytic and sclerotic BM has been acquired in the last decades, leading to the development of bone-targeting agents (BTA), mainly represented by anti-resorptive drugs and bone-seeking radiopharmaceuticals. Recent pre-clinical and clinical studies have showed promising effects of novel agents, whose safety and efficacy need to be confirmed by prospective clinical trials. Among BTA, adjuvant bisphosphonates have also been shown to reduce the risk of BM in selected breast cancer patients, but failed to reduce the incidence of BM from lung and prostate cancer. Moreover, adjuvant denosumab did not improve BM free survival in patients with breast cancer, suggesting the need for further investigation to clarify BTA role in early-stage malignancies. The aim of this review is to describe BM pathogenesis and current treatment options in different clinical settings, as well as to explore the mechanism of action of novel potential therapeutic agents for which further investigation is needed.

[Cohort Study of EGFR-TKIs Combined with Traditional Chinese Medicine and Single EGFR-TKIs for Advanced NSCLC (Non₋small Cell Lung Cancer)].

OBJECTIVE: To explore the curative effect of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKIs) combined with Traditional Chinese Medicine (TCM) versus single EGFR-TKIs for Advanced non-small-cell lung cancer (NSCLC). METHODS: A total of 59 NSCLC patients with EGFR mutation were divided (2:1) into treatment group and control group. Patients in treatment group (39 cases) take EGFR-TKIs plus TCM and control group (20 cases) take EGFR-TKIs. Analysis the progression-free survival (PFS), disease control rate (DCR) and treatment-related adverse events of two groups. RESULTS: The DCR of the treatment group and control group was 94.1% and 84.2% respectively (P=0.24). In the total population, PFS was 12.1 months in treatment group and 9.1 months in control group [hazard ratio (HR) 0.46; 95%CI 0.23-0.9; P=0.025]. Among patients with exon 19 deletion (19-del), PFS between treatment group and control group was 10.5 months and 9.5 months respectively (P=0.17). For patients with exon Leu858Arg point mutation (L858R), PFS was significantly longer with treatment group than withcontrol group (median 13.2 months vs. 7.8 months; HR 0.32, 95%CI 0.10-0.97; P=0.046). Grade 3-4 treatment-related adverse events were less common withtreatment-group (8.33 %) than control group (15.00%) (P=0.65). CONCLUSION: For NSCLC patients with EGFR mutation, EGFR-TKIs combined with TCM has a certain effect to prolong PFS, especially for the patients with L858R.

Laser ablation after stereotactic radiosurgery: a multicenter prospective study in patients with metastatic brain tumors and radiation necrosis.

OBJECTIVE: Laser Ablation After Stereotactic Radiosurgery (LAASR) is a multicenter prospective study of laser interstitial thermal (LITT) ablation in patients with radiographic progression after stereotactic radiosurgery for brain metastases. METHODS: Patients with a Karnofsky Performance Scale (KPS) score ≥ 60, an age > 18 years, and surgical eligibility were included in this study. The primary outcome was local progression-free survival (PFS) assessed using the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. Secondary outcomes were overall survival (OS), procedure safety, neurocognitive function, and quality of life. RESULTS: Forty-two patients­19 with biopsy-proven radiation necrosis, 20 with recurrent tumor, and 3 with no diagnosis­were enrolled. The median age was 60 years, 64% of the subjects were female, and the median baseline KPS score was 85. Mean lesion volume was 6.4 cm3 (range 0.4­38.6 cm3). There was no significant difference in length of stay between the recurrent tumor and radiation necrosis patients (median 2.3 vs 1.7 days, respectively). Progression-free survival and OS rates were 74% (20/27) and 72%, respectively, at 26 weeks. Thirty percent of subjects were able to stop or reduce steroid usage by 12 weeks after surgery. Median KPS score, quality of life, and neurocognitive results did not change significantly for either group over the duration of survival. Adverse events were also similar for the two groups, with no significant difference in the overall event rate. There was a 12-week PFS and OS advantage for the radiation necrosis patients compared with the recurrent tumor or tumor progression patients. CONCLUSIONS: In this study, in which enrolled patients had few alternative options for salvage treatment, LITT ablation stabilized the KPS score, preserved quality of life and cognition, had a steroid-sparing effect, and was performed safely in the majority of cases.

Risk assessment of genotoxic and carcinogenic alkenylbenzenes in botanical containing products present on the Chinese market.

In the present study, a risk assessment of plant food supplements (PFS), traditional Chinese medicines (TCM) and herbal teas containing alkenylbenzenes was performed using the Margin of Exposure (MOE) approach. The levels of alkenylbenzenes in botanical preparations collected on the Chinese market were quantified and the combined estimated daily intake (EDI) was determined using dose additivity. The combined EDI values obtained assuming equal potency of all alkenylbenzenes detected in the PFS, TCM and herbal teas were 0.3 to 14.3, 0.05 to 539.4 and 0.04 to 42.5 µg/kg bw/day, respectively. Calculating combined EDI values taking into account the toxic equivalency (TEQ) approach, the values for PFS, TCM and herbal teas were 0.3 to 7.7, 0.05 to 278.0 and 0.02 to 16.5 µg estragole equivalents/kg bw/day, respectively. The MOE values resulting from consumption of these PFS, TCM and one cup of herbal tea per day during life-time were generally lower than 10 000, suggesting a potential priority for risk management. For short-term exposure such as two weeks consumption, applying Haber's rule, only one TCM 6 () still had an MOE value below 10 000. It is concluded that selected consumption of Chinese botanical preparations raise a concern because of exposure to alkenylbenzenes, especially when exposure is for longer periods of time.

Alternating electric tumor treating fields for treatment of glioblastoma: rationale, preclinical, and clinical studies.

OBJECTIVE Treatment for glioblastoma (GBM) remains largely unsuccessful, even with aggressive combined treatment via surgery, radiotherapy, and chemotherapy. Tumor treating fields (TTFs) are low-intensity, intermediate-frequency, alternating electric fields that have antiproliferative properties in vitro and in vivo. The authors provide an up-to-date review of the mechanism of action as well as preclinical and clinical data on TTFs. METHODS A systematic review of the literature was performed using the terms "tumor treating fields," "alternating electric fields," "glioblastoma," "Optune," "NovoTTF-100A," and "Novocure." RESULTS Preclinical and clinical data have demonstrated the potential efficacy of TTFs for treatment of GBM, leading to several pilot studies, clinical trials, and, in 2011, FDA approval for its use as salvage therapy for recurrent GBM and, in 2015, approval for newly diagnosed GBM. CONCLUSIONS Current evidence supports the use of TTFs as an efficacious, antimitotic treatment with minimal toxicity in patients with newly diagnosed and recurrent GBM. Additional studies are needed to further optimize patient selection, determine cost-effectiveness, and assess the full impact on quality of life.

Exploration of prognostic factors of castration-resistant prostate cancer patients / 中草药

Objective To investigate the prognostic factors of castrated resistant prostate cancer (CRPC). Methods From December 1, 2015 to November 30, 2017, CRPC patients who met the inclusion criteria were collected from the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tumor Hospital of Tianjin Medical University, and General Hospital of Tianjin Medical University. The reliability and validity of 18 included factors were analyzed. The Kaplan-Meier method was used to screen the prognostic factors of CRPC and draw the survival curve.The significant fators from single factor analysis were included in COX proportional risk model for multiple-factor analysis to determine the independent prognostic factors. Results Hematuria, osteodynia, HGB 5.18 mmol/L, TPSA > 10 ng/mL, f/tPSA > 0.19, deficiency of both qi and blood, and no treatment of combination of traditional Chinese medicine were the risk factors for overall survival (OS) in CRPC patients; CHO > 5.18 mmol/L was the only risk factor for OS in CRPC patients, which was established as risk factors. CHO > 5.18 mmol/L, HGB 5.18 mmol/L is an independent risk factor for OS in CRPC patients.

Risk assessment of combined exposure to alkenylbenzenes through consumption of plant food supplements containing parsley and dill.

A risk assessment was performed of parsley- and dill-based plant food supplements (PFS) containing apiol and related alkenylbenzenes. First, the levels of the alkenylbenzenes in the PFS and the resulting estimated daily intake (EDI) resulting from use of the PFS were quantified. Since most PFS appeared to contain more than one alkenylbenzene, a combined risk assessment was performed based on equal potency or using a so-called toxic equivalency (TEQ) approach based on toxic equivalency factors (TEFs) for the different alkenylbenzenes. The EDIs resulting from daily PFS consumption amount to 0.74-125 µg kg-1 bw for the individual alkenylbenzenes, 0.74-160 µg kg-1 bw for the sum of the alkenylbenzenes, and 0.47-64 µg kg-1 bw for the sum of alkenylbenzenes when expressed in safrole equivalents. The margins of exposure (MOEs) obtained were generally below 10,000, indicating a priority for risk management if the PFS were to be consumed on a daily basis. Considering short-term use of the PFS, MOEs would increase above 10,000, indicating low priority for risk management. It is concluded that alkenylbenzene intake through consumption of parsley- and dill-based PFS is only of concern when these PFS are used for long periods of time.

Determination and risk assessment of naturally occurring genotoxic and carcinogenic alkenylbenzenes in nutmeg-based plant food supplements.

A risk assessment of nutmeg-based plant food supplements (PFS) containing different alkenylbenzenes was performed based on the alkenylbenzene levels quantified in a series of PFS collected via the online market. The estimated daily intake (EDI) of the alkenylbenzenes amounted to 0.3 to 312 µg kg-1 body weight (bw) for individual alkenylbenzenes, to 1.5 to 631 µg kg-1 bw when adding up the alkenylbenzene levels assuming equal potency, and to 0.4 to 295 µg kg-1 bw when expressed in safrole equivalents using toxic equivalency factors (TEFs). The margin of exposure approach (MOE) was used to evaluate the potential risks. Independent of the method used for the intake estimate, the MOE values obtained were generally lower than 10000 indicating a priority for risk management. When taking into account that PFS may be used for shorter periods of time and using Haber's rule to correct for shorter than lifetime exposure it was shown that limiting exposure to only 1 or 2 weeks would result in MOE values that would be, with the presently determined levels of alkenylbenzenes and proposed uses of the PFS, of low priority for risk management (MOE > 10000). It is concluded that the results of the present paper reveal that nutmeg-based PFS consumption following recommendations for daily intake especially for longer periods of time raise a concern. Copyright © 2017 John Wiley & Sons, Ltd.