Radiation enhancement using focussed ultrasound-stimulated microbubbles for head and neck cancer: A phase 1 clinical trial.

BACKGROUND AND PURPOSE: Preclinical research demonstrated that the exposure of microbubbles (intravascular gas microspheres) to focussed ultrasound within the targeted tumour upregulates pro-apoptotic pathways and enhances radiation-induced tumour cell death. This study aimed to assess the safety and efficacy of magnetic resonance (MR)-guided focussed ultrasound-stimulated microbubbles (MRgFUS-MB) for head and neck cancers (HN). MATERIALS AND METHODS: This prospective phase 1 clinical trial included patients with newly diagnosed or recurrent HN cancer (except nasopharynx malignancies) for whom locoregional radiotherapy with radical- or palliative-intent as deemed appropriate. Patients with contraindications for microbubble administration or contrast-enhanced MR were excluded. MR-coupled focussed ultrasound sonicated intravenously administered microbubbles within the MR-guided target volume. Patients receiving 5-10 and 33-35 radiation fractions were planned for 2 and 3 MRgFUS-MB treatments, respectively. Primary endpoint was toxicity per CTCAEv5.0. Secondary endpoint was tumour response at 3 months per RECIST 1.1 criteria. RESULTS: Twelve patients were enrolled between Jun/2020 and Nov/2023, but 1 withdrew consent. Eleven patients were included in safety analysis. Median follow-up was 7 months (range, 0.3-38). Most patients had oropharyngeal cancer (55 %) and received 20-30 Gy/5-10 fractions (63 %). No systemic toxicity or MRgFUS-MB-related adverse events occurred. The most severe acute adverse events were radiation-related grade 3 toxicities in 6 patients (55 %; dermatitis in 3, mucositis in 1, dysphagia in 6). No radiation necrosis or grade 4/5 toxicities were reported. 8 patients were included in the 3-month tumour response assessment: 4 had partial response (50 %), 3 had complete response (37.5 %), and 1 had progressive disease (12.5 %). CONCLUSIONS: MRgFUS-MB treatment was safe and associated with high rates of tumour response at 3 months.

Valproic acid as a radio-sensitizer in glioma: A systematic review and meta-analysis.

Background: Histone deacetylase inhibitors (HDACi) including valproic acid (VPA) have the potential to improve radiotherapy (RT) efficacy and reduce treatment adverse events (AE) via epigenetic modification and radio-sensitization of neoplastic cells. This systematic review and meta-analysis aimed to assess the efficacy and AE associated with HDACi used as radio-sensitizers in adult solid organ malignancy patients. Methods: A systematic review utilized electronic searches of MEDLINE(Ovid), Embase(Ovid), The Cochrane Library, and the International Clinical Trials Registry Platform to identify studies examining the efficacy and AEs associated with HDACi treatment in solid organ malignancy patients undergoing RT. Meta-analysis was performed with overall survival (OS) reported as hazard ratios (HR) as the primary outcome measure. OS reported as median survival difference, and AEs were secondary outcome measures. Results: Ten studies reporting on the efficacy and/or AEs of HDACi in RT-treated solid organ malignancy patients met inclusion criteria. All included studies focused on HDACi valproic acid (VPA) in high-grade glioma patients, of which 9 studies (n = 6138) evaluated OS and 5 studies (n = 1055) examined AEs. The addition of VPA to RT treatment protocols resulted in improved OS (HR = 0.80, 95% CI 0.67-0.96). No studies focusing on non-glioma solid organ malignancy patients, or non-VPA HDACi met the inclusion criteria for this review. Conclusions: This review suggests that glioma patients undergoing RT may experience prolonged survival due to HDACi VPA administration. Further randomized controlled trials are required to validate these findings. Additionally, more research into the use of HDACi radio-adjuvant treatment in non-glioma solid organ malignancies is warranted.

Pharmacologic inhibition of ataxia telangiectasia and Rad3-related (ATR) in the treatment of head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) poses significant treatment challenges, with high recurrence rates for locally advanced disease despite aggressive therapy typically involving a combination of surgery, radiation therapy, and/or chemotherapy. HNSCCs commonly exhibit reduced or absent TP53 function due to genomic alterations or human papillomavirus (HPV) infection, leading to dependence on the S- and G2/M checkpoints for cell cycle regulation. Both of these checkpoints are activated by Ataxia Telangiectasia and Rad3-related (ATR), which tends to be overexpressed in HNSCC relative to adjacent normal tissues and represents a potentially promising therapeutic target, particularly in combination with other treatments. ATR is a DNA damage signaling kinase that is activated in response to replication stress and single-stranded DNA breaks, such as those induced by radiation therapy and certain chemotherapies. ATR kinase inhibitors are currently being investigated in several clinical trials as part of the management of locally advanced, recurrent, or metastatic HNSCC, along with other malignancies. In this review article, we summarize the rationale and preclinical data supporting incorporation of ATR inhibition into therapeutic regimens for HNSCC.

A phase III study of transdermal granisetron versus oral ondansetron for women with gynecologic cancers receiving pelvic chemoradiation.

PURPOSE: To compare rates of complete response (no emesis, retching, or rescue antiemetics) in the late phase (days 4-7 post-chemotherapy) of cycle 1 between transdermal granisetron and oral ondansetron in cervical, endometrial, or vaginal cancer survivors undergoing chemoradiation at The University of Texas MD Anderson Cancer Center and LBJ Hospital in Houston, TX. METHODS: In this non-blinded parallel design trial, eligible patients received a granisetron patch replaced every 7 days or 8 mg of ondansetron thrice daily continued for 72 h after chemotherapy completion. Data were collected on medication compliance, episodes of chemotherapy-induced nausea and vomiting (CINV), use of rescue antiemetics, and effects of CINV on quality of life. RESULTS: Seventy-five survivors receiving chemoradiation for cervical (n = 61), endometrial (n = 12), or vaginal (n = 2) cancer were electronically randomized to transdermal granisetron (n = 41) or oral ondansetron (n = 34). In the late phase of cycle 1, the rate of complete response was 49.8% (95% CI, 35.2-64.3%) for transdermal granisetron and 39.7% (95% CI, 24.4-56.1%) for oral ondansetron. The posterior probability that transdermal granisetron achieved a higher success rate in controlling late-onset CINV compared with oral ondansetron was 82%. During the acute phase (day 1 post-chemotherapy) of cycles 2 and 3, transdermal granisetron patients used more rescue antiemetics than oral ondansetron patients (p = 0.006 and p = 0.003, respectively). Otherwise, no between-group differences in CINV events were observed. Medication compliance and the effect of CINV on quality of life were similar between groups. CONCLUSION: Transdermal granisetron was 82% more like to control CINV than oral ondansetron in the late phase of cycle 1 and performed similarly to oral ondansetron in all other cycles. Transdermal granisetron should be considered an option as prophylactic antiemetic therapy for gynecologic cancer survivors undergoing chemoradiation.

Evaluating the Radiosensitization Effect of Hydroxyapatite Nanoparticles on Human Breast Adenocarcinoma Cell Line and Fibroblast.

BACKGROUND: Nanohydroxyapatite (nHAP) exhibit anti-proliferative effects on various cancer cells. However, to date, there are only a few studies on the radiosensitization effect of nHAP. The present study aimed to investigate the possible enhancement of the radiosensitization effect of nHAP on human breast adenocarcinoma cancer (MCF-7) and fibroblast. METHODS: nHAP was extracted from fish scales using the thermal alkaline method and characterized at Babol University of Medical Sciences (Babol, Iran) in 2017. The anti-proliferative and the radiosensitization effects of nHAP were investigated by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium Bromide (MTT), clonogenic assay, and apoptosis assay. MCF-7 cells and fibroblasts were incubated with different concentrations of nHAP and at different periods. The MTT solution was added and the absorbance was measured at 570 nm. The MCF-7 cells were exposed to 0, 1.5, 3.5, and 5 Gy X-ray irradiation and incubated for 10-14 days. The data were compared using the one-way analysis of variance (ANOVA) followed by the post hoc tests (Tukey's method). RESULTS: The results showed that nHAP significantly inhibited the growth of MCF-7 cells compared with controls (P<0.001), but the difference was not statistically significant for fibroblasts (P=0.686 at 400 µg/mL at 72 hours). After 48 hours, the proliferation of MCF-7 cells and fibroblasts was inhibited by about 81% and 34% at 400 µg/mL concentration, respectively. The radiosensitization enhancement factor for MCF-7 cells and fibroblasts at a dose of 3.5 Gy and 100 µg/mL concentration were 1.87 and 1.3, respectively. CONCLUSION: nHAP can be considered as a breast cancer radiosensitization agent with limited damage to the surrounding healthy tissue.

Metformin: (future) best friend of the radiation oncologist?

Several molecules are being investigated for their ability to enhance the anti-tumor effect of radiotherapy. The widely prescribed antidiabetic drug metformin has been suggested to possess anti-cancer activity; data indicate that metformin could also enhance radiation sensitivity. The purpose of this review is to summarize current knowledge on the specific effect of metformin in the field of RT, while also discussing the many unknowns that persist. Preclinical models point to multiple mechanisms involved in the radiosensitizing effects of metformin that are mainly linked to mitochondrial complex I inhibition and AMP-activated protein kinase. Transposition of results from bench to bedside will be discussed through the lens of the drug concentration, its potential limits in human settings, and possible alternatives. Clinical data suggest metformin improves progression-free and overall survival in patients for many different cancers treated with RT; nevertheless, the results are not always consistent. The main limitations of the reviewed literature are the retrospective nature of studies, and most of the time, a lack of information on MTF treatment duration and the administered dosages. Despite these limitations, the possible mechanisms of the role of metformin and its utility in enhancing radiotherapy treatments are analyzed. Ongoing clinical trials are also discussed.

Investigation of the Dose-Enhancement Effects of Spherical and Rod-Shaped Gold Nanoparticles on the HeLa Cell Line.

BACKGROUND: Cervical cancer cells are known as radioresistant cells. Current treatment methods have not improved the patients' survival efficiently; thus, new therapeutic strategies are needed to enhance the efficacy of radiotherapy. Gold nanomaterials with different shapes and sizes have been explored as radiosensitizers. The present study compared the radiosensitizing effects of gold nanorods (AuNRs) with spherical gold nanoparticles (AuNPs) on the HeLa cell line irradiated with megavoltage X-rays. MATERIALS AND METHODS: The cytotoxicity of AuNRs and AuNPs on HeLa cells in the presence and absence of 6-MV X-ray was investigated using the MTT assay. For this aim, HeLa cells were incubated with and AuNPs and AuNRs at various concentrations (5, 10, and 15 µg/mL) for 6 hours. Afterward, HeLa cells were irradiated with 6-MV X-ray at a single dose of 2 Gy. RESULTS: The results showed that the addition of AuNRs and AuNPs could enhance the radiosensitivity of HeLa cells. Both AuNRs and AuNPs showed low toxicity on HeLa cells, while AuNRs were more toxic than AuNPs at the examined concentrations. Moreover, it was found that AuNRs could enhance the radiosensitivity of HeLa cells more than spherical-shaped AuNPs. CONCLUSION: This study revealed that the shape of nanoparticles is an effective factor when they are used as radiosensitizing agents during radiotherapy.

Overcoming radioresistance in WiDr cells with heavy ion irradiation and radiosensitization by 2-deoxyglucose with photon irradiation.

BACKGROUND AND PURPOSE: Radiosensitizers and heavy ion irradiation could improve therapy for female patients with malignant tumors located in the pelvic region through dose reduction. Aim of the study was to investigate the radiosensitizing potential of 2-deoxy-d-glucose (2-DG) in combination with carbon ion-irradiation (12C) in representative cell lines of cancer in the female pelvic region. MATERIALS AND METHODS: The human cervix carcinoma cell line CaSki and the colorectal carcinoma cell line WiDr were used. 2-DG was employed in two different settings, pretreatment and treatment simultaneous to irradiation. Clonogenic survival, α and ß values for application of the linear quadratic model and relative biological effectiveness (RBE) were determined. ANOVA tests were used for statistical group comparison. Isobolograms were generated for curve comparisons. RESULTS: The comparison of monotherapy with 12C versus photons yielded RBE values of 2.4 for CaSki and 3.5 for WiDr along with a significant increase of α values in the 12C setting. 2-DG monotherapy reduced the colony formation of both cell lines. Radiosensitization was found in WiDr for the combination of photon irradiation with synchronous application of 2-DG. The same setup for 12C showed no radiosensitization, but rather an additive effect. In all settings with CaSki, the combination of irradiation and 2-DG exhibited additive properties. CONCLUSION: The combination of 2-DG and photon therapy, as well as irradiation with carbon ions can overcome radioresistance of tumor cells such as WiDr.

Application of nanomaterials in enhancing internal radiotherapy of radionuclide for cancer / 中华核医学与分子影像杂志

The therapeutic efficiency of radionuclides for cancer is closely related to the accumula-tion level, residence time and distribution in tumor, and is also influenced by the radiation resistance and hypoxia microenvironment of tumor. Nanomaterials, with a series of characteristics including special dimen-sion effect and functionally modifiable surface, can not only work as the isotopic carrier to transport nuclide into tumor, but also combine with chemical, thermal or photodynamic therapies to generate synergistic thera-peutic effect or destroy the hypoxic microenvironment of tumor to reduce radiation resistance, thus achieving the radiosensitization effect. This article reviews the application of nanomaterials in enhancing the therapeu-tic efficiency of radionuclide for cancer.

Radiosensitization of sodium glycididazole in esophageal cancer evaluated by 18F-FMISO PET/CT / 中华核医学与分子影像杂志

Objective To investigate the feasibility of sodium glycididazole(CMNa)on the radio-sensitization of esophageal cancer(EC)by 18F-fluoromisonidazole(FMISO)PET/CT.Methods A total of 60 patients with EC from December 2016 to December 2017 were enrolled prospectively and were divided into control group(n = 30;21 males,9 females;age:(56.6±10.0)years)and experimental group(n=30;20 males,10 females;age:(59.3±9.0)years)using completely randomized grouping design.Patients in the control group received radiotherapy alone,and those in the experimental group were treated with conventional radiotherapy and CMNa.All patients underwent 18F-FMISO PET/CT imaging 1 week before and after radiotherapy.The imaging results were visually and semi-quantitatively analyzed.The maximum standardized uptake value(SUVmax),tumor/muscle ratio(T/M),and hypoxia volume(HV)were calculated.Paired t test,two-sample t test and/x2 test were used to analyze the data.Results T/M and HV in the control group before and after radiotherapy were 3.92±0.57 vs 1.66±0.35,(1.84±0.31)vs(1.04±0.15)mm3,respectively;T/M and HV in the experimental group before and after radiotherapy were 4.01±0.68 vs 1.27±0.11,(2.01±0.22)vs(0.90±0.09)mm3,respectively.The primary tumor T/M,HV after radiotherapy in 2 groups were significantly lower than those before radiotherapy(t values:12.15-24.43,all P<0.05)and the amplitudes of T/M and HV in the experimental group were significantly higher than those in the control group(?T/M:2.77±0.60vs 2.25±0.49,?HV:(1.12±0.18)vs(0.81±0.26)mm3;t values:3.00 and 1.80,both P<0.05).Meanwhile,the local control rate of EC after 3 months in the experimental group was higher than that in the control group(80.0%(24/30)vs 53.3%(16/30);x2=4.80,P<0.05).Conclusion CMNa has the radiosensitizing effect on EC and the 18F-FMISO PET/CT can evaluate the radiosensitization effect.

Reirradiation + hyperthermia for recurrent breast cancer en cuirasse.

BACKGROUND AND PURPOSE: Patients with irresectable locoregional recurrent breast cancer en cuirasse (BCEC) do not have effective curative treatment options. Hyperthermia, the elevation of tumor temperature to 40-45 °C, is a well-established radio- and chemotherapy sensitizer. A total of 196 patients were treated with reirradiation and hyperthermia (reRT+HT) at two Dutch institutes from 1982-2005. The palliative effect was evaluated in terms of clinical outcome and toxicity. PATIENTS AND METHODS: All patients received previous irradiation to a median dose of 50 Gy. In all, 75% of patients received 1-6 treatment modalities for previous tumor recurrences. ReRT consisted of 8 × 4 Gy given twice a week or 12 × 3 Gy given four times a week. Superficial hyperthermia was added once or twice a week. Tumor area comprised ≥½ of the ipsilateral chest wall. RESULTS: Overall clinical response rate was 72% (complete response [CR] 30%, partial response [PR] 42%, stable disease [SD] 22%, progressive disease [PD] 6%). The local progression-free rate at 1 year was 24%. Median survival was 6.9 months. Forty-three percent of our patients with CR, PR, SD after treatment remained infield progression-free until death or last follow-up. Acute ≥grade 3 toxicity occurred in 33% of patients, while late ≥grade 3 toxicity was recorded in 14% of patients. Tumor ulceration prior to treatment had a negative impact on both clinical outcome and toxicity. CONCLUSION: ReRT+HT provides sustainable palliative tumor control, despite refractory, extensive tumor growth. Compared to currently available systemic treatment options, reRT+HT is more effective with less toxicity.

Evaluation of radiosensitivity enhancement by irisquinone with 18F-FETNIM microPET/CT imaging in breast cancer bearing nude mice / 中华核医学与分子影像杂志

Objective To investigate the effect of irisquinone (IR) on the radiosensitization of MDA-MB-231 breast cancer in nude mice using 18F-fluoroerythronitroimidazole (18F-FETNIM) microPET/ CT.Methods Thirty-two nude mice bearing MDA-MB-231 breast cancer were divided into 4 groups by random number table method (n =8 for each group):group A was treated with radiotherapy alone,group B was treated with radiotherapy and IR,group C was treated with IR alone,and group D was fed with distilled water.18F-FETNIM microPET/CT images were obtained to monitor the maximum standardized uptake value (SUVmax) of tumor before radiotherapy and 24 h after radiotherapy.The mice were sacrificed and tumor tissues were removed for HE staining.The expression of hypoxia inducible factor-1α (HIF-1α) was detected by immunohistochemical (IHC) method.Data were analyzed by paired t test,one-way analysis of variance,the least significant different t test and Pearson correlation analysis.Results There was no significant difference in SUVmax among the 4 groups before radiotherapy (1.429±0.090,1.430±0.076,1.445±0.071,1.432± 0.074;F=0.072,P＞0.05).At 24 h after radiotherapy,the SUVmax of group A and B decreased significantly (1.075±0.098,0.890±0.076;t values:12.888,33.217,both P＜0.05),and there was significant difference between group B and group A (t =4.197,P＜0.05).However,the SUVmax of group C and D increased significantly (1.617±0.090,1.644±0.063;t values:-11.009,-16.061,both P＜0.05).Pathological results showed that tumor cells in group A and B were reduced.IHC results showed that the expression of HIF-1α was lower in group B than others ((26.75±7.19)％;F=46.745,t values:2.898-9.743,all P＜ 0.05).The expression of HIF-1α was positively correlated with SUVmax(r =0.89,P＜0.05).Conclusion 18F-FETNIM microPET/CT could evaluate the radiosensitization effect of IR on MDA-MB-231 breast cancer in nude mice.

In Vitro Radiosensitizing Effects of Temozolomide on U87MG Cell Lines of Human Glioblastoma Multiforme.

BACKGROUND: Glioma is the most common primary brain tumor with poor prognosis. Temozolomide (TMZ) has been used with irradiation (IR) to treat gliomas. The aim of the present study was to evaluate the cytotoxic and radiosensitizing effect of TMZ when combined with high-dose and high-dose rate of gamma irradiation in vitro. METHODS: Two 'U87MG' cell lines and skin fibroblast were cultured and assigned to five groups for 24, 48, and 72 hours. The groups were namely, TMZ group (2000 µM/L), IR group (5 Gy), TMZ plus IR group, control group, and control solvent group. MTT assay was applied to evaluate cell viability. Data were analyzed with SPSS 21.0 software using one-way ANOVA and Kruskal-Wallis test. P<0.05 were considered statistically significant. RESULTS: The slope of growth curve U87MG cells in semi-logarithmic scale was equal to 27.36±0.89 hours. The viability of cells was determined for different TMZ and IR treatment groups. In terms of cell viability, there were no significant differences between the control and control solvent groups (P=0.35) and between treated group by IR (5 Gy) alone and TMZ (2000 µM/ml) alone (P=0.15). Data obtained for the cell viability of combined TMZ plus IR in both cell lines compared to TMZ or IR treated group alone showed a significant difference (P=0.002). CONCLUSION: The evaluation of cells viability showed that TMZ in combination with IR on glioma cells led to a significant radiosensitivity compared to IR alone.

Novel drug targets in radiosensitivity of neoplasms / 国际肿瘤学杂志

Recent studies find a number of promising drug targets which can be applied for increasing tumor radiosensitivity in addition to normal tissue radioprotection,including oxygen free radical scavenger,drug targets in view of DNA damage repair and cell cycle,new targets inhibiting cell death,radioprotection mediated by growth factors,regulation of the cell signaling pathways,angiotensin-converting enzyme inhibitor.radiorestorative chemicals and so on.

Overcoming radioresistance in head and neck squamous cell carcinoma.

Radiation therapy plays an essential role in the treatment of head and neck squamous cell carcinoma (HNSCC), yet therapeutic efficacy is hindered by treatment-associated toxicity and tumor recurrence. In comparison to other cancers, innovation has proved challenging, with the epidermal growth factor receptor (EGFR) antibody cetuximab being the only new radiosensitizing agent approved by the FDA in over half a century. This review examines the physiological mechanisms that contribute to radioresistance in HNSCC as well as preclinical and clinical data regarding novel radiosensitizing agents, with an emphasis on those with highest translational promise.

Docetaxel-induced radiation recall dermatitis : A case report and literature review.

Radiation recall dermatitis (RRD) refers to an acute inflammatory skin reaction appearing on a previously irradiated area following the systemic administration of a reaction-triggering agent. Despite various hypotheses, the pathomechanism of RRD appears complex and is still not fully understood. In addition, no clinical guidelines exist concerning whether drug treatment should be continued upon manifestation of an associated radiation recall phenomenon. We present the case of a patient with docetaxel-induced RRD, which was successfully treated with topical steroids and systemic antihistamines; re-challenge to docetaxel did result in very mild remanifestation of skin reactions.

Caffeic Acid Phenethyl Ester Increases Radiosensitivity of Estrogen Receptor-Positive and -Negative Breast Cancer Cells by Prolonging Radiation-Induced DNA Damage.

PURPOSE: Breast cancer is an important cause of death among women. The development of radioresistance in breast cancer leads to recurrence after radiotherapy. Caffeic acid phenethyl ester (CAPE), a polyphenolic compound of honeybee propolis, is known to have anticancer properties. In this study, we examined whether CAPE enhanced the radiation sensitivity of MDA-MB-231 (estrogen receptor-negative) and T47D (estrogen receptor-positive) cell lines. METHODS: The cytotoxic effect of CAPE on MDA-MB-231 and T47D breast cancer cells was evaluated by performing an 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. To assess clonogenic ability, MDA-MB-231 and T47D cells were treated with CAPE (1 µM) for 72 hours before irradiation, and then, a colony assay was performed. A comet assay was used to determine the number of DNA strand breaks at four different times. RESULTS: CAPE decreased the viability of both cell lines in a dose- and time-dependent manner. In the clonogenic assay, pretreatment of cells with CAPE before irradiation significantly reduced the surviving fraction of MDA-MB-231 cells at doses of 6 and 8 Gy. A reduction in the surviving fraction of T47D cells was observed relative to MDA-MB-231 at lower doses of radiation. Additionally, CAPE maintained radiation-induced DNA damage in T47D cells for a longer period than in MDA-MB-231 cells. CONCLUSION: Our results indicate that CAPE impairs DNA damage repair immediately after irradiation. The induction of radiosensitivity by CAPE in radioresistant breast cancer cells may be caused by prolonged DNA damage.

Analysis of esophageal cancer cell lines exposed to X-ray based on radiosensitivity influence by tumor necrosis factor-α.

Assess the effects of tumor necrosis factor-α (TNF-α) in enhancing the radiosensitivity of esophageal cancer cell line in vitro. Three esophageal cancer cell line cells were exposed to X-ray with or without TNF-α treatment. MTT assay was used to evaluate the cell growth curve, and flow cytometry was performed to assess the cell apoptosis. The radiosensitizing effects of TNF-α were detected by cell colony formation assay. Western blotting was applied to observe the expression of NF-κB and caspase-3 protein in the exposed cells. Our results indicated that cellular inhibition rate increased over time, the strongest is combined group (P < 0.05). Western blotting showed that the decline expression of NF-κB protein was stated between only rhTNF-α and only X-ray radiation group and the maximum degree was manifested in combined group. Caspase-3 protein content expression just works opposite. Three kinds of cells in the NF-κB protein were similar without rhTNF-α. Then SEG1 NF-κB protein content was reduced more than other two kinds. We concluded that the cells treated with TNF-α showed significantly suppressed cell proliferation, increasing the cell apoptosis, and caspase-3 protein expression after X-ray exposure. TNF-α can enhance the radiosensitivity of esophageal cancer to enhancing the effect of the former.

Patterns of prescribing radiotherapy and bevacizumab in nationwide practice - analysis of 101 designated cancer care hospitals in Japan.

Radiotherapy and bevacizumab are each effective in treating patients with advanced cancer, but their concurrent use may cause serious adverse events (SAEs). Whereas sequential administration can theoretically reduce the risk of SAEs while maintaining the anticancer effects, this hypothesis remains unconfirmed, leading to variations in practice. To elucidate current practices, the patterns of care received by patients in Japan with regard to these two therapies were assessed in a large database of a hospital-based cancer registry linked with insurance claims. This database contained information on 106 057 patients diagnosed with seven major cancers in 2011 and the care they received up to the end of 2012. In total, 335 patients from 101 hospitals in the database were treated with both radiotherapy and bevacizumab. Of these patients, 50.8% had lung cancer, and 51.3% had Stage IV cancer. Of the 335 patients, 75 (22.4%) received these therapies concurrently. In patients treated sequentially, the time from the last dose of bevacizumab to the start of radiotherapy was most frequently 4-5 weeks (12.4%), whereas the time from the end of radiotherapy to the start of bevacizumab was most frequently 1-2 weeks (10.6%). The cumulative proportions of patients in these two groups receiving sequential therapies within 3 weeks were 19.0% and 26.1%, respectively. Many practices appeared to avoid the concurrent use of bevacizumab and radiation, but some provided concurrent therapy. Additional data are required to determine whether the avoidance of concurrent use should become a standard of care.

Determination of content and related substances of radiosensitizer benzotriazine derivatives YABQ by HPLC / 军事医学

Objective To establish an HPLC method for determination of the content of radiosensitizer YABQ and its related substances.Methods Diamonsil C18 column (250 mm ×4.6 mm,5 μm) was used.The mobile phase consisted of methanol-0.1%formic acid (22∶78) and isocratic elution at a flow rate of 1.0 ml/min.The detection wavelength was 266 nm,the temperature of the column was 30℃, and the injection volume was 10 μl.Results The linear range of YABQ was 7-84 μg/ml, r=0.9992.The detection limit was 8 ng (S/N≥3), and the quantitation limit was 24 ng (S/N≥10). According to destructive sample processing, the separation coefficient between the peaks was above 1.5, indicating that this chromatographic method could meet the YABQ monitoring requirements.Conclusion Method validation and destructive testing show that both the precision and specificity are fine with this method, which could be used for quality control of YABQ and its related substances.