Optimizing the cancer research landscape for the benefit of patients and society: A strategic perspective of the German Cancer Research Center (DKFZ) and its partnerships with university medical centers

This issue of Cancer Biology & Medicine, a premium Chinese international scientific journal in this field, focuses on cooperation between Chinese and German cancer research, particularly between the Tianjin Medical University Cancer Institute & Hospital and the German Cancer Research Center(DKFZ) with its networking partners. This editorial provides a brief overview on DKFZ’s research strategy with a focus on how a national integrated cancer research and care ecosystem is evolving that benefits patients and society.

GIPC1 promotes tumor growth and migration in gastric cancer via activating PDGFR/PI3K/AKT signaling

The high mortality rate associated with gastric cancer(GC)has resulted in an urgent need to identify novel therapeutic targets for GC.This study aimed to investigate whether GAIP interacting protein,C terminus 1(GIPC1)represents a therapeutic target and its regulating mechanism in GC.GIPC1 expression was elevated in GC tissues,liver metastasis tissues,and lymph node metastases.GIPC1 knockdown or GIPC1 blocking peptide blocked the platelet-derived growth factor receptor(PDGFR)/PI3K/AKT signaling pathway,and inhibited the proliferation and migration of GC cells.Conversely,GIPC1 overexpression markedly activated the PDGFR/PI3K/AKT signaling pathway,and promoted GC cell proliferation and migration.Furthermore,platelet-derived growth factor subunit BB(PDGF-BB)cytokines and the AKT inhibitor attenuated the effect of differential GIPC1 expression.Moreover,GIPC1 silencing decreased tumor growth and migration in BALB/c nude mice,while GIPC1 overexpression had contrasting effects.Taken together,our findings suggest that GIPC1 functions as an oncogene in GC and plays a central role in regulating cell proliferation and migration via the PDGFR/PI3K/AKT signaling pathway.

Ki-67 Change in Anthracyline-containing Neoadjuvant Chemotherapy Response in Breast Cancer

Objective Anthracycline-containing regimens are irreplaceable in neoadjuvant chemotherapy(NAC)for breast cancer(BC)at present.However,30% of early breast cancer(EBC)patients are resistant to anthracycline-containing chemotherapy,leading to poor prognosis and higher mortality.Ki-67 is associated with the prognosis and response to therapy,and it changes after NAC.Methods A total of 105 BC patients who received anthracycline-containing NAC were enrolled.Then,the optimal model of Ki-67 was selected,and its predictive efficacy was analyzed.Immunohistochemistry(IHC)was used to determine the estrogen receptor(ER),progesterone receptor(PR),and human epidermal growth factor receptor 2(HER-2)status and Ki-67 level.Fluorescent in situ hybridization(FISH)was used to verify the HER-2 when the IHC score was 2+.Results The post-NAC Ki67 level after treatment with anthracycline drugs was lower than pre-NAC Ki-67(19.6%±23.3%vs.45.6%±23.1%,P<0.001).Furthermore,patients with the Ki-67 decrease had a border line higher pathological complete response(pCR)rate(17.2%vs.0.0%,P=0.068),and a higher overall response rate(ORR)(73.6%vs.27.8%,P<0.001),when compared to patients without the Ki-67 decrease.The ΔKi-67 and ΔKi-67%were valuable markers for the prediction of both the pCR rate and ORR.The area under the curve(AUC)for ΔKi-67 on pCR and ORR was 0.809(0.698-0.921)and 0.755(0.655-0.855),respectively,while the AUC for ΔKi-67% on pCR and ORR was 0.857(0.742-0.972)and 0.720(0.618-0.822),respectively.Multivariate logistic regression model 1 revealed thatΔKi-67 was an independent predictor for both pCR[odds ratio(OR)=61.030,95% confidence interval(CI)=4.709-790.965;P=0.002]and ORR(OR=10.001,95%CI:3.044-32.858;P<0.001).Multivariate logistic regression model 2 revealed thatΔKi-67%was also an independent predictor for both pCR(OR=408.922,95%CI=8.908-18771.224;P=0.002)and ORR(OR=5.419,95%CI=1.842-15.943;P=0.002).Conclusions The present study results suggest thatΔKi67 andΔKi67%are candidate predictors for anthracycline-containing NAC response,and that they may provide various information for further systematic therapy after surgery in clinical practice.

Celecoxib enhances the response of tumor cells to cisplatin through upregulating PUMA in non–small cell lung cancer carrying wild-type p53

Celecoxib,a cyclooxygenase-2 inhibitor,can enhance the efficacy of chemotherapy;however,its effect seems inconsistent.In this study,we investigated whether celecoxib would increase the antiproliferative effects of cisplatin in human lung cancer cells.Our data demonstrated the synergistic effects of celecoxib with cisplatin in wild-type p53 cells and their antagonistic effects inmutated or deleted p53 cells.Combination indices of 0.82 to 0.93 reflected a synergistic effect between celecoxib and cisplatin in lung cancer cells with wild-type p53.Combination indices of 1.63 to 3.00 reflected antagonism between celecoxib and cisplatin in lung cancer cells with mutated or deleted p53.Compared with that in cells with mutated or deleted p53,apoptosis significantly increased with the addition of celecoxib and cisplatin in wild-type p53 cells(P<0.05).Moreover,the results in vivo were similar to those in vitro:celecoxib combinedwith cisplatin slowed tumor growth in wild-type p53 groups and not in mutated or deleted p53 groups.In addition,celecoxib promoted p53 translocation into the nucleus and upregulated active p53 expression in wild-type p53 cells.Celecoxib combined with cisplatin upregulated PUMA(PUMA is a downstream gene of p53)after active p53 increased in wild-type p53 cells.In summary,the combination of celecoxib and cisplatin demonstrates clear synergistic effects in wild-type p53 cells and antagonistic effects inmutated or deleted p53 cells.The synergistic effect was achieved by apoptosis,induced by upregulating PUMA.Our results will provide a new treatment strategy for patients carrying wild-type p53,insensitive to cisplatin.

Palliative chemotherapy for gastroesophageal cancer in old and very old patients: A retrospective cohort study at the National Center for Tumor Diseases, Heidelberg

AIM:To investigate the outcome of palliative chemotherapy in old patients with gastroesophageal cancer at the National Center for Tumor Diseases,Heidelberg.METHODS:Using a prospectively generated database,we retrospectively analyzed 55 patients≥70years under palliative chemotherapy for advanced gastroesophageal cancer at the outpatient clinic of the National Center for Tumor Diseases Heidelberg,Germany between January 2006 and December2013.Further requirements for inclusion were(1)histologically proven diagnosis of gastroesophageal cancer;(2)advanced(metastatic or inoperable)disease;and(3)no history of radiation or radiochemotherapy.The clinical information included Eastern Cooperative Oncology Group performance status(ECOG PS),presence and site of metastases at diagnosis,date of previous surgery and perioperative chemotherapy,start and stop date of first-line treatment,toxicities and consecutive dosage reductions of first-line treatment,response to first-line therapy,date of progression,usage of second-line therapies and date and cause of death.Survival times[progression-free survival(PFS),overall survival(OS)and residual survival(RS)]were calculated.Toxicity and safety were examined.Prognostic factors including ECOG PS,age and previousperioperative treatment were analyzed.RESULTS:Median age of our cohort was 76 years.86%of patients received a combination of two cytotoxic drugs.76 percent of patients had an oxaliplatin-based first-line therapy with the oxaliplatin and 5-fluorouracil regimen being the predominantely chosen regimen(69%).Drug modifications due to toxicity were necessary in 56%of patients,and 11%of patients stopped treatment due to toxicities.Survival times of our cohort are in good accordance with the major phaseⅢtrials that included mostly younger patients:PFS and OS were 5.8 and 9.5 mo,respectively.Survival differed significantly between patient groups with low(≤1)and high(≥2)ECOG PS(12.7 mo vs 3.8 mo,P<0.001).Very old patients(≥75 years)did not show a worse outcome in terms of survival.Patients receiving secondline treatment(51%)had a significantly longer RS than patients with best supportive care(6.8 vs 1.4 mo,P=0.001).Initial ECOG PS was a strong prognostic factor for PFS,OS and RS.CONCLUSION:Old patients with non-curable gastroesophageal cancer should be offered chemotherapy,and ECOG PS is a tool for balancing benefit and harm upfront.Second-line treatment is reasonable.

Advances in prostate cancer research models:From transgenic mice to tumor xenografting models

The identification of the origin and molecular characteristics of prostate cancer(PCa)has crucial implications for personalized treatment.The development of effective treatments for PCa has been limited;however,the recent establishment of several transgenicmouse lines and/or xenografting models is better reflecting the disease in vivo.With appropriate models,valuable tools for elucidating the functions of specific genes have gone deep into prostate development and carcinogenesis.In the present review,we summarize a number of important PCa research models established in our laboratories(PSA-Cre-ERT2/PTEN transgenic mouse models,AP-OX model,tissue recombination-xenografting models and PDX models),which represent advances of translational models from transgenic mouse lines to human tumor xenografting.Better understanding of the developments of these models will offer new insights into tumor progression and may help explain the functional significance of genetic variations in PCa.Additionally,this understanding could lead to new modes for curing PCa based on their particular biological phenotypes.

Imaging in translational cancer research

This review is aimed at presenting some of the recent developments in translational cancer imaging research,with a focus on novel,recently established,or soon to be established cross-sectional imaging techniques for computed tomography(CT),magnetic resonance imaging(MRI),and positron-emission tomography(PET)imaging,including computational investigations based on machine-learning techniques.

Tumor organoids for cancer research and personalized medicine

Organoids are three-dimensional culture systems generated from embryonic stem cells,induced pluripotent stem cells,and adult stem cells.They are capable of cell proliferation,differentiation,and self-renewal.Upon stimulation by signal factors and/or growth factors,organoids self-assemble to replicate the morphological and structural characteristics of the corresponding organs.They provide an extraordinary platform for investigating organ development and mimicking pathological processes.Organoid biobanks derived from a wide range of carcinomas have been established to represent different lesions or stages of clinical tumors.Importantly,genomic and transcriptomic analyses have confirmed maintenance of intra-and interpatient heterogeneities in organoids.Therefore,this technology has the potential to revolutionize drug screening and personalized medicine.In this review,we summarized the characteristics and applications of organoids in cancer research by the establishment of organoid biobanks directly from tumor organoids or from genetically modified non-cancerous organoids.We also analyzed the current state of organoid applications in drug screening and personalized medicine.

Neutrophils as key regulators of tumor immunity that restrict immune checkpoint blockade in liver cancer

Objective:Liver cancer is a deadly malignancy associated with high mortality and morbidity.Less than 20%of patients with advanced liver cancer respond to a single anti-PD-1 treatment.The high heterogeneity of neutrophils in the tumor immune microenvironment in liver cancer may contribute to resistance to immune checkpoint blockade(ICB).However,the underlying mechanism remains largely unknown.Methods:We established an orthotopic liver cancer model by using transposable elements to integrate the oncogenes Myc and KrasG12Dinto the genome in liver cells from conditional Trp53 null/null mice(pTMK/Trp53^(-/-)).Flow cytometry and immunohistochemistry were used to assess the changes in immune cells in the tumor microenvironment.An ex vivo coculture assay was performed to test the inhibitory effects of tumor-associated neutrophils(TANs)on CD8^(+)T cells.The roles of neutrophils,T cells,and NK cells were validated through antibody-mediated depletion.The efficacy of the combination of neutrophil depletion and ICB was evaluated.Results:Orthotropic pTMK/Trp53^(-/-)mouse liver tumors displayed a moderate response to anti-Ly6G treatment but not PD-1 blockade.Depletion of neutrophils increased the infiltration of CD8^(+)T cells and decreased the number of exhausted T cells in the tumor microenvironment.Furthermore,depletion of either CD8^(+)T or NK cells abrogated the antitumor efficacy of anti-Ly6G treatment.Moreover,the combination of anti-Ly6G with anti-PD-L1 enhanced the infiltration of cytotoxic CD8^(+)T cells and thereafter resulted in a significantly greater decrease in tumor burden.Conclusions:Our data suggest that TANs may contribute to the resistance of liver cancer to ICB,and combining TAN depletion with T cell immunotherapy synergistically increases antitumor efficacy.

Establishing a breast cancer center in Herat,Afghanistan:an implementation study

Objective:Breast cancer is the most common cancer in women,causing significant mortality in the world,which contributed 11.7%to the overall cancer-related mortality in Afghanistan.In 2018,3062 new breast cancer cases were reported accounting for 29.7%of all cancers in women in the country.However,a comprehensive diagnostic and therapeutic system is lacking in Afghanistan.In this paper,we reported the implementation of a project aiming to establish a comprehensive breast cancer center in Herat province of Afghanistan.Methods:From July 2017,a two-year-program initiated at Kimia Hospital in Herat.This first free diagnostic and therapeutic breast cancer project planned by the Afghanistan Surgeons Society-West and the Verein für Afghanistan-Förderung e.V.,as well supported by three international foundations.The target populations of this project were women presenting with breast problems at Kimia Hospital in Herat and healthcare staff involved in breast cancer diagnosis and management.Results:A group of six medical personnel chosen to represent the breast cancer core team for breast cancer diagnosis and management were trained in India.These caregivers established the breast cancer service and tumor board.During a period of 20 months,a total of 632 women with breast problems presented to Kimia Hospital of whom 44(7.0%)were diagnosed with breast cancer.Diagnosis was established by a physical examination,ultrasonography,mammography,biopsy and histopathology.Treatment included surgery,radiotherapy and chemotherapy.Twelve seminars for 512 healthcare workers,1000 brochures and a movie were prepared for awareness-raising actions.For continuation of this project,potential resource providers were identified.A database was developed to record project findings.Conclusion:Implementation of this comprehensive breast cancer project resulted in significant achievements in healthcare staff capacity building,diagnosis and management of breast cancer patients in Herat province.Data obtained in this project offer Afghan government,public health authorities,and the community the opportunity of improving diagnosis and treatment of breast cancer in Afghanistan.

Th1 cells inducing IFNγ response improves immunotherapy efficacy in gastric cancer

Objective: Cancer immunotherapy has made remarkable advances in recent years, but its effectiveness in treating gastric cancer is often limited by the complexity of the tumor microenvironment and the lack of effective biomarkers. This study aimed to identify effective biomarkers for immunotherapy treatment by characterizing the tumor microenvironment.Methods: We retrieved the RNA-seq data from gastric cancer patients treated with the programmed death 1(PD-1) blockade pembrolizumab. Differentially expressed genes associated with clinical outcomes were identified and further analyzed using gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis. Gene signature scores were calculated by single sample Gene Set Enrichment Analysis(ssGSEA). The infiltration levels of immune cells were quantified using the xCell website. Cell type enrichment analysis was performed to compare treatment response and non-response groups, and regression analysis was used to investigate the relationship between interferon gamma(IFNγ) immune response and immune cell infiltration. Biomarkers were identified using least absolute shrinkage and selection operator(LASSO) analysis.Results: Compared to normal tissues, cytokine activity and interleukin-6 production were highly activated in gastric tumors. Responders to pembrolizumab showed significantly up-regulated expression of IFNγ responserelated genes. Cell type enrichment analysis revealed that Th1 cells were significantly enriched in the tumor microenvironment of responders. Regression analysis indicated that Th1 cells induced IFNγ response more efficiently than other cell types. Using signatures of Th1 cells, stromal cells and IFNγ response, a set of eight genes were identified that effectively predicted the efficacy of immunotherapy treatment and patient prognosis.Conclusions: Th1 cells promote therapeutic efficacy of PD-1 blockade by promoting IFNγ immune response in gastric cancer. The identified biomarkers have the potential to improve the effectiveness of immunotherapy treatment for gastric cancer patients.

Azoximer bromide and hydroxyapatite:promising immune adjuvants in cancer

Immune adjuvants are immune modulators that have been developed in the context of infectious vaccinations.There is currently a growing interest in immune adjuvants due to the development of immunotherapy against cancers.Immune adjuvant mechanisms of action are focused on the initiation and amplification of the inflammatory response leading to the innate immune response,followed by the adaptive immune response.The main activity lies in the support of antigen presentation and the maturation and functions of dendritic cells.Most immune adjuvants are associated with a vaccine or incorporated into the new generation of m RNA vaccines.Few immune adjuvants are used as drugs.Hydroxyapatite(HA)ceramics and azoximer bromide(AZB)are overlooked molecules that were used in early clinical trials,which demonstrated clinical efficacy and excellent tolerance profiles.HA combined in an autologous vaccine was previously developed in the veterinary field for use in canine spontaneous lymphomas.AZB,an original immune modulator derived from a class of heterochain aliphatic polyamines that is licensed in Russia,the Commonwealth of Independent States,and Slovakia for infectious and inflammatory diseases,is and now being developed for use in cancer with promising results.These two immune adjuvants can be combined in various immunotherapy strategies.

Comparison of the effects of high-intensity interval and moderate-intensity continuous training on inflammatory markers,cardiorespiratory fitness,and quality of life in breast cancer patients

Background:As the effectiveness of breast cancer treatment has improved,a growing number of long-term breast cancer survivors are seeking help for unique health problems.These patients may be at increased risk of cardiovascular disease due to the side effects of treatment.The positive impact of most types of exercise has been repeatedly reported in people with cancer,but the most effective exercise approaches for maximum beneficial adaptations remain controversial.Thus,this study aimed to compare the effects of high-intensity interval training(HIIT)and moderate-intensity continuous training(MICT) on inflammatory indices,adipokines,metabolic markers,body composition,cardiorespiratory fitness,and quality of life in breast cancer patients during adjuvant endocrine therapy.Methods:Thirty non-metastatic breast cancer patients during adjuvant endocrine therapy who had been treated with chemotherapy and/or radiotherapy were recruited from Iran and randomized to HIIT,MICT,or control groups for a supervised exercise intervention that took place 3 times a week for 12 weeks.The training intensity was determed based on the peak oxygen uptake(VO2peak),and the volume of training was matched in HIIT and MICT based on the VO2peak.Body composition,functional capacity,cardiorespiratory fitness,metabolic indices,sex hormones,adipokines,and inflammatory markers were assessed before and after the intervention.Results:The VO2peakincreased by 16.8% in the HIIT group in comparison to baseline values(mean difference=3.61 mL/kg/min).HIIT significantly improved the VO2peakcompared to control(mean difference=3.609 mL/kg/min) and MICT(mean differences=2.974 mL/kg/min)groups.Both HIIT(mean difference=9.172 mg/dL) and MICT(mean difference=7.879 mg/dL) interventions significantly increased highdensity lipoprotein cholesterol levels compared to the control group.The analysis of covariance showed that physical well-being significantly improved in MICT compared to control group(mean difference=3.268).HIIT significantly improved the social well-being compared to the control group(mean difference=4.412).Emotional well-being subscale was significantly improved in both MICT(mean difference=4.248)and HIIT(mean difference=4.412) compared to the control group.Functional well-being scores significantly increased in HIIT group compared with control group(mean difference=3.35).Significant increase were also observed in total functional assessment of cancer therapy-General scores in both HIIT(mean difference=14.204) and MICT groups(mean difference=10.036) compared with control group.The serum level of suppressor of cytokine signaling 3 increased significantly(mean difference=0.09 pg/mL) in the HIIT group compared to the baseline.There were no significant differences between groups for body weight,body mass index,fasting blood glucose,insulin resistance,sex hormone binding globulin,total cholesterol,low-density lipoprotein cholesterol,adipokines,interleukin-6,tumor necrosis factor-a,or interleukin-10.Conclusion:HIIT can be used as a safe,feasible,and time-efficient intervention to improve cardiovascular fitness in breast cancer patients.Both HIIT and MICT modalities enhance quality of life.Further large-scale studies will help determine whether these promising results translate into improved clinical and oncological outcomes.

LipoCol Forte capsules reduce the risk of liver cancer:A propensity score-matched,nationwide,population-based cohort study

BACKGROUND Liver cancer is among the top five most common cancers globally. Lipid-lowering drugs such as statins can lower the risk of liver cancer, but may also cause liver damage. LipoCol Forte capsules(LFC), a red yeast rice product, have demonstrated significant antihypercholesterolemic effects and a good safety profile in clinical studies.AIM To evaluate whether LFC lowers the risk of liver cancer in adults in this propensity score-matched, nationwide, population-based cohort study.METHODS We used data from Taiwan’s National Health Insurance Research Database, which includes electronic medical records for up to 99.99% of Taiwan’s population. LFC users and LFC non-users were matched 1:1 by propensity scores between January 2010 and December 2017. All had followup data for at least 1 year. Statistical analyses compared demographic distributions including sex, age, comorbidities, and prescribed medications. Cox regression analyses estimated adjusted hazard ratios(aHRs) after adjusting for potential confounders.RESULTS We enrolled 33231 LFC users and 33231 non-LFC users(controls). No significant differences between the study cohorts were identified regarding comorbidities and medications [standardized mean difference(SMD) < 0.05]. At follow-up, the overall incidence of liver cancer was significantly lower in the LFC cohort compared with controls [aHR 0.91;95% confidence interval(CI): 0.86-0.95;P < 0.001]. The risk of liver cancer was significantly reduced in both females(aHR 0.87;95%CI: 0.8-0.94;P < 0.001) and males(aHR 0.93;95%CI: 0.87-0.98;P < 0.01) in the LFC cohort compared with their counterparts in the non-LFC cohort. The antitumor protective effects applied to patients with comorbidities(including hypertension, ischemic stroke, diabetes mellitus, hyperlipidemia, hepatitis B infection and hepatitis C infection). Those using LFC for more than 84 drug days had a 0.64-fold lower risk of liver cancer compared with controls(P < 0.001). Compared with controls, the risk of developing liver cancer in the LFC cohort progressively decreased over time;the lowest incidence of liver cancer occurred in LFC users followed-up for more than 6 years(27.44 vs 31.49 per 1,000 person-years;aHR 0.75;95%CI: 0.68-0.82;P < 0.001).CONCLUSION This retrospective cohort study indicates that LFC has a significantly protective effect on lowering the risk of liver cancer, in a dose-dependent and time-dependent manner.

Medical expenditures for colorectal cancer diagnosis and treatment: A 10-year high-level-hospital-based multicenter retrospective survey in China, 2002-2011

Objective: Colorectal cancer(CRC) causes a substantial burden of disease in China and the evidence of economic burden triggered is fundamental for priority setting. The aim of this survey was to quantify medical expenditures and the time trends for CRC diagnosis and treatment in China.Methods: From 2012 to 2014, a hospital-based multicenter retrospective survey was conducted in 13 provinces across China. For each eligible CRC patient diagnosed from 2002 to 2011, clinical information and expenditure data were extracted using a uniform questionnaire. All expenditure data were reported in Chinese Yuan(CNY)using 2011 values.Results: Of the 14,536 CRC patients included, the average age at diagnosis was 58.2 years and 15.8% were stageI cases. The average medical expenditure per patient was estimated at 37,902 CNY [95 % confidence interval(95%CI): 37,282-38,522], and the annual average increase rate was 9.2% from 2002 to 2011(P for trend <0.001), with a cumulative increase of 2.4 times(from 23,275 CNY to 56,010 CNY). The expenditure per patient in stages Ⅰ, Ⅱ, Ⅲ and Ⅳ were 31,698 CNY, 37,067 CNY, 38,918 CNY and 42,614 CNY, respectively(P<0.001). Expenditure significantly differed within various subgroups. Expenses for drugs contributed the largest proportion(52.6%).Conclusions: These conservative estimates illustrated that medical expenditures for CRC diagnosis and treatment in tertiary hospitals in China were substantial and increased rapidly over the 10 years, with drugs continually being the main expense by 2011. Relatively, medical expenditures are lower for CRC in the earlier stages. These findings will facilitate the economic evaluation of CRC prevention and control in China.

基于放疗科大孔径CT的自适应迭代重建技术在肺结节穿刺中的应用研究

目的:研究大孔径CT自适应统计迭代重建(ASIR)对肺结节经皮穿刺中图像质量的影响。方法:选取2023年1月—7月于深圳市宝安区人民医院接受大孔径CT引导穿刺的肺结节患者20例。分别应用滤波反投影技术(FBP)和ASIR技术重建图像并评价两组图像质量。主观评价采用Likert评分,客观评价对结节区噪声标准差(SD)、对比噪声比(CNR)和穿刺针针尖位置CT值等资料。结果:图像的主观评价均满足穿刺要求且一致性较好(Kappa值=0.740)。ASIR图像质量随着权重先增加后降低,权重为60%时最佳。和FBP相比,ASIR 60%的Likert评分更高,结节SD和CNR值比较,差异有统计学意义(P=0.004、0.043)。其他统计参数比较,差异均没有统计学意义(P>0.05)。结论:放疗用大孔径CT常规扫描不影响穿刺图像质量,ASIR 60%图像质量更优,可以用于引导肺结节经皮穿刺。

Expenditure and financial burden for the diagnosis and treatment of colorectal cancer in China:a hospital.based,multicenter,cross-sectional survey

Background: The increasing prevalence of colorectal cancer(CRC) in China and the paucity of information about relevant expenditure highlight the necessity of better understanding the financial burden and effect of CRC diagnosis and treatment. We performed a survey to quantify the direct medical and non-medical expenditure as well as the resulting financial burden of CRC patients in China.Methods: We conducted a multicenter, cross-sectional survey in 37 tertiary hospitals in 13 provinces across China between 2012 and 2014. Each enrolled patient was interviewed using a structured questionnaire. All expenditure data were inflated to the 2014 Chinese Yuan(CNY; 1 CNY = 0.163 USD). We quantified the overall expenditure and financial burden and by subgroup(hospital type, age at diagnosis, sex, education, occupation, insurance type, household income, clinical stage, pathologic type, and therapeutic regimen). We then performed generalized linear modeling to determine the factors associated with overall expenditure.Results: A total of 2356 patients with a mean age of 57.4 years were included, 57.1 % of whom were men; 13.9% of patients had stage I cancer; and the average previous-year household income was 54,525 CNY.The overall average direct expenditure per patient was estimated to be 67,408 CNY, and the expenditures for stage Ⅰ, Ⅱ, Ⅲ, and Ⅳ disease were 56,099 CNY, 59,952 CNY, 67,292 CNY, and 82,729 CNY, respectively. Non-medical expenditure accounted for 8.3%of the overall expenditure. The 1-year out-of-pocket expenditure of a newly diagnosed patient was 32,649 CNY, which accounted for 59.9% of their previous-year household income and caused 75.0% of families to suffer an unmanageable financial burden. Univariate analysis showed that financial burden and overall expenditure differed in almost all subgroups(P < 0.05), except for sex. Multivariate analysis showed that patients who were treated in specialized hospitals and those who were diagnosed with adenocarcinoma or diagnosed at a later stage were likely to spend more,whereas those with a lower household income and those who underwent surgery spent less(all P < 0.05).Conclusions: For patients in China, direct expenditure for the diagnosis and treatment of CRC seemed catastrophic,and non-medical expenditure was non-ignorable. The financial burden varied among subgroups, especially among patients with different clinical stages of disease, which suggests that, in China, CRC screening might be cost-effective.

Medical expenditure for esophageal cancer in China:a 10-year multicenter retrospective survey(2002-2011)

Background: Esophageal cancer is associated with substantial disease burden in China, and data on the economic burden are fundamental for setting priorities in cancer interventions. The medical expenditure for the diagnosis and treatment of esophageal cancer in China has not been fully quantified. This study aimed to examine the medical expenditure of Chinese patients with esophageal cancer and the associated trends.Methods: From 2012 to 2014, a hospital-based multicenter retrospective survey was conducted in 37 hospitals in 13 provinces/municipalities across China as a part of the Cancer Screening Program of Urban China. For each esophageal cancer patient diagnosed between 2002 and 2011, clinical information and expense data were extracted by using structured questionnaires. All expense data were reported in Chinese Yuan(CNY; 1 CNY = 0.155 USD) based on the2011 value and inflated using the year-specific health care consumer price index for China.Results: A total of 14,967 esophageal cancer patients were included in the analysis. It was estimated that the overall average expenditure per patient was 38,666 CNY, and an average annual increase of 6.27% was observed from 2002(25,111 CNY) to 2011(46,124 CNY). The average expenditures were 34,460 CNY for stage Ⅰ,39,302 CNY for stage Ⅱ,40,353 CNY for stage Ⅲ, and 37,432 CNY for stage IV diseases(P < 0.01). The expenditure also differed by the therapy type, which was 38,492 CNY for surgery, 27,933 CNY for radiotherapy, and 27,805 CNY for chemotherapy(P < 0.05).Drugs contributed to 45.02% of the overall expenditure.Conclusions: These conservative estimates suggested that medical expenditures for esophageal cancer in China substantially increased in the last 10 years, treatment for early-stage esophageal cancer costs less than that for advanced cases, and spending on drugs continued to account for a considerable proportion of the overall expenditure.

GNL3蛋白在胃癌中的表达及其在细胞增殖、侵袭以及迁移中的作用

目的探讨鸟嘌呤核苷酸结合蛋白样3(guanine nucleotide binding protein-like 3,GNL3)蛋白在胃癌中的表达,探明GNL3蛋白在胃癌增殖、迁移及侵袭等生物学功能中的作用。方法数据库分析GNL3 mRNA在胃癌组织中的表达情况;采用免疫组化SP法检测51例胃癌组织和对应癌旁正常组织中GNL3蛋白表达;χ^(2)检验分析GNL3蛋白表达与胃癌临床病理特征之间的关系;通过转染小发夹RNA(small hairpin RNA,sh-RNA)沉默胃癌细胞中GNL3的表达,并应用Western blot法验证沉默效率。采用CCK-8、平板克隆和EdU实验检测沉默GNL3对胃癌细胞增殖能力的影响。采用细胞划痕和Transwell实验检测沉默GNL3对胃癌细胞侵袭和迁移能力的影响。结果SangerBox和UALCAN数据库检索结果显示,GNL3 mRNA在胃癌组织中的表达显著增加(P均<0.01)。免疫组化结果显示,GNL3蛋白在胃癌组织中的阳性率(96.1%)和高表达率(78.4%)显著高于癌旁组织(74.5%、51.0%,P<0.01),并且GNL3高表达与胃癌淋巴结转移(χ^(2)=4.933,P=0.026)具有相关性。CCK-8、平板克隆以及EdU实验结果显示,沉默GNL3可抑制胃癌细胞SGC-7901的增殖能力。细胞划痕和Transwell实验结果显示,沉默GNL3可抑制胃癌细胞SGC-7901的迁移和侵袭能力。结论GNL3蛋白在胃癌组织中高表达,且与胃癌细胞增殖、迁移及侵袭能力密切相关。

赖氨酰氧化酶LOXL2稳定性的理论计算研究

赖氨酰氧化酶LOXL2是一种依赖于铜离子的胺氧化酶,催化胶原蛋白和弹性蛋白的赖氨酸残基侧链发生氧化脱氨,发挥着稳固细胞外基质的作用。而稳定性是蛋白质的一个重要特性,直接影响蛋白质的分子动态及其正常功能发挥,这与人类的健康和疾病密切相关。然而,关于LOXL2的稳定性目前鲜有报道,哪些位点对其稳定性有显著影响尚不清楚。本研究采用冷冻电镜和Alphafold2的数据,建立LOXL2的全长结构,通过分子动力学模拟得到其优化构象。再通过4种方法(mCSM,PremPS,DeepDDG和FoldX),计算所有位点的稳定性属性,筛选出对稳定性有显性影响的位点(定义为关键位点)。结果表明,95个关键位点对LOXL2的稳定性具有显著影响,在5个结构域上的分布数量依次为14、13、8、11和26,而结构域间的连接肽段上也有23个关键位点。在这些关键位点中,类型及数量分别为Leu(24个)、Val(20个)、Ile(12个)、Trp(11个)、Phe(11个)、Tyr(6个)、Cys(6个)、Met(4个)和Arg(1个)。其中大部分关键位点(88个)为疏水性质,这与蛋白质折叠的主要力量为疏水作用的情况是一致的,而Cys两两成对,构成二硫键,对LOXL2的结构及功能发挥重要作用。讨论中,我们将预测结果与实验值进行比较,并用自由能微扰方法,对部分关键位点进行比较,从多方面论证此项工作的可信度。此项研究,可为靶向LOXL2的疾病治疗研究,提供重要指导。