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 Medica...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.展开更多
Background The potential of exercise as a concurrent therapy for actively treated primary tumors has been suggested by emerging preclinical and observational studies.However,clinical trials regarding this question are...Background The potential of exercise as a concurrent therapy for actively treated primary tumors has been suggested by emerging preclinical and observational studies.However,clinical trials regarding this question are scarce.Therefore,we conducted a randomized controlled trial investigating the effects of aerobic or resistance exercise concomitant to neoadjuvant chemotherapy(NACT)on tumor size.Methods In the BENEFIT study(German title:Bewegung bei neoadjuvanter chemotherapie zur verbesserung der fitness),patients with breast cancer scheduled for NACT were randomly assigned to supervised resistance training(RT,n=60)or aerobic training(AT,n=60)twice weekly during NACT or to a waitlist control group(WCG,n=60).The primary outcome,“change in tumor size”,as well as the secondary clinical outcomes pathologic complete response(pCR),type of surgery(breast conserving/mastectomy),axillary lymph node dissection(ALND,yes/no),premature discontinuation of chemotherapy(yes/no),and relative dose intensity(RDI)were derived from clinical records.Due to the highly skewed distribution,the primary outcome was categorized.Multiple(ordinal)logistic regression analyses were performed.Results Overall,there was no significant difference in post-intervention tumor size between RT or AT and WCG.However,there was a significant effect modification by hormone receptor(HR)status(P_(interaction)=0.030).Among patients with HR+tumors,results suggest a beneficial effect of AT on tumor shrinkage(odds ratio(OR)=2.37,95%confidence interval(95%CI):0.97‒5.78),on pCR(OR=3.21,95%CI:0.97‒10.61);and on ALND(OR=3.76,95%CI:0.78‒18.06)compared to WCG.The effects of RT were slightly less pronounced.For HR−subtypes,beneficial effects on RDI were found for AT(OR=3.71,95%CI:1.20‒11.50)and similarly for RT(OR=2.58,95%CI:0.88‒7.59).Both AT and RT had favorable effects on premature discontinuation of chemotherapy(OR(no vs.yes)=2.34,95%CI:1.10‒5.06),irrespective of tumor receptor status.Conclusion While there was no significant effect on the primary outcome in the overall group,aerobic and resistance exercise concomitant to NACT seem to beneficially affect tumor shrinkage and pCR,reduce the need for ALND among patients with HR+breast cancers,and prevent low RDI among patients with HR–breast cancers.These results warrant confirmation in further trials.展开更多
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 retrospec...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.展开更多
Lung cancer is the most common cancer type worldwide and has the highest and second highest mortality rate for men and women respectively in Germany.Yet,the role of comorbid illnesses in lung cancer patient prognosis ...Lung cancer is the most common cancer type worldwide and has the highest and second highest mortality rate for men and women respectively in Germany.Yet,the role of comorbid illnesses in lung cancer patient prognosis is still debated.We analyzed administrative claims data from one of the largest statutory health insurance(SHI)funds in Germany,covering close to 9 million people(11%of the national population);observation period was from 2005 to 2019.Lung cancer patients and their concomitant diseases were identified by ICD-10-GM codes.Comorbidities were classified according to the Charlson Comorbidity Index(CCI).Incidence,comorbidity prevalence and survival are estimated considering sex,age at diagnosis,and place of residence.Kaplan Meier curves with 95%confidence intervals were built in relation to common comorbidities.We identified 70,698 lung cancer incident cases in the sample.Incidence and survival figures are comparable to official statistics in Germany.Most prevalent comorbidities are chronic obstructive pulmonary disease(COPD)(36.7%),followed by peripheral vascular disease(PVD)(18.7%),diabetes without chronic complications(17.4%),congestive heart failure(CHF)(16.5%)and renal disease(14.7%).Relative to overall survival,lung cancer patients with CHF,cerebrovascular disease(CEVD)and renal disease are associated with largest drops in survival probabilities(9%or higher),while those with PVD and diabetes without chronic complications with moderate drops(7%or lower).The study showed a negative association between survival and most common comorbidities among lung cancer patients,based on a large sample for Germany.Further research needs to explore the individual effect of comorbidities disentangled from that of other patient characteristics such as cancer stage and histology.展开更多
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 c...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.展开更多
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 ...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.展开更多
AIM:To investigate biological prevention with flavonoids the recurrence risk of neoplasia was studied in patients with resected colorectal cancer and after adenoma polypectomy.METHODS:Eighty-seven patients,36 patients...AIM:To investigate biological prevention with flavonoids the recurrence risk of neoplasia was studied in patients with resected colorectal cancer and after adenoma polypectomy.METHODS:Eighty-seven patients,36 patients with resected colon cancer and 51 patients after polypectomy,were divided into 2 groups:one group was treated with a flavonoid mixture(daily standard dose 20 mg apigenin and 20 mg epigallocathechin-gallat,n=31)and compared with a matched control group(n=56).Both groups were observed for 3-4 years by surveillance colonoscopy and by questionnaire.RESULTS:Of 87 patients enrolled in this study,36 had resected colon cancer and 29 of these patients had surveillance colonoscopy.Among the flavonoid-treated patients with resected colon cancer(n=14),there was no cancer recurrence and one adenoma developed.In contrast the cancer recurrence rate of the 15 matched untreated controls was 20%(3 of 15)and adenomas evolved in 4 of those patients(27%).The combined recurrence rate for neoplasia was 7%(1 of 14)in the treated patients and 47%(7 of 15)in the controls(P=0.027).CONCLUSION:Sustained long-term treatment with a flavonoid mixture could reduce the recurrence rate of colon neoplasia in patients with resected colon cancer.展开更多
The tumor microenvironment is an ecosystem composed of multiple types of cells, such as tumor cells, immune cells, and cancerassociated fibroblasts. Cancer cells grow faster than non-cancerous cells and consume larger...The tumor microenvironment is an ecosystem composed of multiple types of cells, such as tumor cells, immune cells, and cancerassociated fibroblasts. Cancer cells grow faster than non-cancerous cells and consume larger amounts of nutrients. The rapid growth characteristic of cancer cells fundamentally alters nutrient availability in the tumor microenvironment and results in reprogramming of immune cell metabolic pathways. Accumulating evidence suggests that cellular metabolism of nutrients, such as lipids and amino acids, beyond being essential to meet the bioenergetic and biosynthetic demands of immune cells, also regulates a broad spectrum of cellular signal transduction, and influences immune cell survival, differentiation, and anti-tumor effector function. The cancer immunometabolism research field is rapidly evolving, and exciting new discoveries are reported in high-profile journals nearly weekly. Therefore, all new findings in this field cannot be summarized within this short review. Instead, this review is intended to provide a brief introduction to this rapidly developing research field, with a focus on the metabolism of two classes of important nutrients-lipids and amino acids-in immune cells. We highlight recent research on the roles of lipids and amino acids in regulating the metabolic fitness and immunological functions of T cells, macrophages, and natural killer cells in the tumor microenvironment. Furthermore, we discuss the possibility of “editing” metabolic pathways in immune cells to act synergistically with currently available immunotherapies in enhancing anti-tumor immune responses.展开更多
Lung cancer remains the leading cause of cancer-associated mortality worldwide,but with the emergence of oncogene targeted therapies,treatment options have tremendously improved.Owing to their biological relevance,mem...Lung cancer remains the leading cause of cancer-associated mortality worldwide,but with the emergence of oncogene targeted therapies,treatment options have tremendously improved.Owing to their biological relevance,members of the ERBB receptor family,including the EGF receptor(EGFR),HER2,HER3 and HER4,are among the best studied oncogenic drivers.Activating EGFR mutations are frequently observed in non-small cell lung cancer(NSCLC),and small molecule tyrosine kinase inhibitors(TKIs)are the established first line treatment option for patients whose tumors bear"typical/classical"EGFR mutations(exon 19 deletions,L858R point mutations).Additionally,new TKIs are rapidly evolving with better efficacy to overcome primary and secondary treatment resistance(e.g.,that due to T790M or C797S resistance mutations).Some atypical EGFR mutations,such as the most frequent exon 20 insertions,exhibit relative resistance to earlier generation TKIs through steric hindrance.In this subgroup,newer TKIs,such as mobocertinib and the bi-specific antibody amivantamab have recently been approved,whereas less frequent atypical EGFR mutations remain understudied.In contrast to EGFR,HER2 has long remained a challenging target,but better structural understanding has led to the development of newer generations of TKIs.The recent FDA approval of the antibody-drug conjugate trastuzumab-deruxtecan for pretreated patients with HER2 mutant NSCLC has been an important therapeutic breakthrough.HER3 and HER4 also exert oncogenic potential,and targeted treatment approaches are being developed,particularly for HER3.Overall,strategies to inhibit the oncogenic function of ERBB receptors in NSCLC are currently evolving at an unprecedented pace;therefore,this review summarizes current treatment standards and discusses the outlook for future developments.展开更多
AIM： TO explore the role of Bcl-XL and Myeloid cell leukaemia （Mcl）-I for the apoptosis resistance of colorectal carcinoma （CRC） cells towards current treatment modalities. METHODS： Bcl-XL and Mcl-1 mRNA and pro...AIM： TO explore the role of Bcl-XL and Myeloid cell leukaemia （Mcl）-I for the apoptosis resistance of colorectal carcinoma （CRC） cells towards current treatment modalities. METHODS： Bcl-XL and Mcl-1 mRNA and protein expression were analyzed in CRC cell lines as well as human CRC tissue by Western blot, quantitative PCRand immunohistochemistry. Bcl-XL and Mcl-1 protein expression was knocked down or increased in CRC cell lines by applying specific siRNAs or expression plasmids, respectively. After modulation of protein expression, CRC cells were treated with chemotherapeutic agents, an antagonistic epidermal growth factor receptor （EGFR1） antibody, an EGFR1 tyrosine kinase inhibitor, or with the death receptor ligand TRAIL. Apoptosis induction and cell viability were analyzed. RESULTS： Here we show that in human CRC tissue and various CRC cell lines both Bcl-xL and Mcl-1 are expressed. Bcl-xL expression was higher in CRC tissue than in surrounding non-malignant tissue, both on protein and mRNA level. Mcl-1 mRNA expression was significantly lower in malignant tissues. However, protein expression was slightly higher. Viability rates of CRC cells were significantly decreased after knock down of Bcl-xL expression, and, to a lower extent, after knock down of Mcl-1 expression. Furthermore, cells with reduced Bcl-xL or Mcl-1 expression was more sensitive towards oxaliplatinand irinotecan-induced apoptosis, and in the case of Bcl-xL also towards 5-FU-induced apoptosis. On the other hand, upregulation of Bcl-xL by transfection of an expression plasmid decreased chemotherapeutic drug-induced apoptosis. EGF treatment clearly induced Bcl-xL and Mcl-1 expression in CRC cells. Apoptosis induction upon EGFR1 blockage by cetuximab or PD168393 was increased by inhibiting Mcl-1 and Bcl-xL expression. More strikingly, CD95- and TRAIL-induced apoptosis was increased by Bcl-xL knock down. CONCLUSION： Our data suggest that Bcl-xL and, to a lower extent, Mcl-1, are important anti-apoptotic factors in CRC. Specific downregulation of Bcl-xL is a promising approach to sensitize CRC cells towards chemotherapy and targeted therapy.展开更多
Objective:We aimed to directly compare the estimated effects of adherence to a healthy lifestyle with those of risk predisposition according to known genetic variants affecting colorectal cancer(CRC)risk,to support ef...Objective:We aimed to directly compare the estimated effects of adherence to a healthy lifestyle with those of risk predisposition according to known genetic variants affecting colorectal cancer(CRC)risk,to support effective risk communication for cancer prevention.Methods:A healthy lifestyle score(HLS)was derived from 5 lifestyle factors:smoking,alcohol consumption,diet,physical activity,and body adiposity.The association of lifestyle and polygenic risk score(PRS)(based on 140 CRC-associated risk loci)with CRC risk was assessed with multiple logistic regression and compared through the genetic risk equivalent(GRE),a novel approach providing an estimate of the effects of adherence to a healthy lifestyle in terms of percentile differences in PRS.Results:A higher HLS was associated with lower CRC risk(4,844 cases,3,964 controls).Those adhering to all 5 healthy lifestyle factors had a 62%(95%CI 54%-68%)lower CRC risk than those adhering to≤2 healthy lifestyle factors.The estimated effect of adherence to all 5 compared with≤2 healthy lifestyle factors was as strong as the effect of having a 79 percentile(GRE 79,95%CI 61-97)lower PRS.The association between a healthy lifestyle and CRC risk was independent of PRS level but was particularly pronounced among those with a family history of CRC in≥1 first-degree relative(P-interaction=0.0013).Conclusions:A healthy lifestyle was strongly inversely associated with CRC risk.The large GRE indicated that CRC risk determined by polygenic risk may be offset to a substantial extent by adherence to a healthy lifestyle.展开更多
Pancreatic cancer has a considerably poor prognosis with a 5-year survival probability of less than 5% when all stages are combined. Pancreatic cancer is characterized by its dense stroma, which is involved in the cri...Pancreatic cancer has a considerably poor prognosis with a 5-year survival probability of less than 5% when all stages are combined. Pancreatic cancer is characterized by its dense stroma, which is involved in the critical interplay with the tumor cells throughout tumor progression and furthermore, creates a barrier restricting efficient penetration of therapeutics. Alterations in a large number of genes are reflected by a limited number of signaling pathways, which are potential targets. Understanding more about the molecular basis of this devastating cancer type regarding tumor microenvironment, distinct subpopulations of cells, epithelial-to-mesenchymal transition and inflammation will lead to the development of various targeted therapies for controlling tumor growth and metastasis. In this complex scenario of pancreatic cancer, especially members of the “small integrin binding ligand N-linked glycoproteins” (SIBLINGs) and “secreted protein acidic and rich in cysteine” (SPARC) families have emerged due to their prominent roles in properties including proliferation, differentiation, apoptosis, adhesion, migration, angiogenesis, wound repair and regulation of extracellular matrix remodeling. SIBLINGs consist of five members, which include osteopontin (OPN), bone sialoprotein, dentin matrix protein 1, dentin sialophosphoprotein and matrix extracellular phosphoglycoprotein. The SPARC family of modular extracellular proteins is comprised of SPARC/osteonectin (ON) and SPARC-like 1 (hevin); secreted modular calcium binding proteins; testicans and follistatin-like protein. In this review, we especially focus on OPN and ON, elaborating on their special and growing importance in pancreatic cancer diagnosis and prognosis.展开更多
This review summarizes the current status of neoadjuvantradiation approaches in the treatment of pancreatic cancer,including a description of modern radiation techniques,and an overview on the literature regarding neo...This review summarizes the current status of neoadjuvantradiation approaches in the treatment of pancreatic cancer,including a description of modern radiation techniques,and an overview on the literature regarding neoadjuvantradio- or radiochemotherapeutic strategies both forresectable and irresectable pancreatic cancer. Neoadjuvantchemoradiation for locally-advanced, primarily non- orborderline resectable pancreas cancer results in secondaryresectability in a substantial proportion of patients withconsecutively markedly improved overall prognosisand should be considered as possible alternative inpretreatment multidisciplinary evaluations. In resectablepancreatic cancer, outstanding results in terms ofresponse, local control and overall survival have beenobserved with neoadjuvant radio- or radiochemotherapy inseveral phase Ⅰ/Ⅱ trials, which justify further evaluationof this strategy. Further investigation of neoadjuvantchemoradiation strategies should be performed preferentiallyin randomized trials in order to improvecomparability of the current results with other treatmentmodalities. This should include the evaluation of optimalsequencing with newer and more potent systemicinduction therapy approaches. Advances in patientselection based on new molecular markers might be ofcrucial interest in this context. Finally modern externalbeam radiation techniques (intensity-modulated radiationtherapy, image-guided radiation therapy and stereotacticbody radiation therapy), new radiation qualities (protons,heavy ions) or combinations with alternative boostingtechniques widen the therapeutic window and contributeto the reduction of toxicity.展开更多
This paper reports the prevalence of chronic esophagitis and nutritional status among 538 young persons aged 15 to 26 years from the high risk area for esophageal cancer. Of these subjects, 166 were from households wi...This paper reports the prevalence of chronic esophagitis and nutritional status among 538 young persons aged 15 to 26 years from the high risk area for esophageal cancer. Of these subjects, 166 were from households with history of esophageal cancer and 372 were from households without history of esophageal cancer. The Incidences of chronic esophagltis among male and female adolescents were 37. 6% and 36% respectively, which was significantly higher than those in the low risk area (17%). The frequency of chronic esophagltis in the adolescents in the households with history of esophageal cancer was aiso higher than in those In the households without history of esophageal cancer. The deficiencies of vitamins, especially of riboflavin and ascorbate, are prevalent and severe among these adolescents. Ascorbate deficiency Is correlated with the severity of the chronic esophagltis. These results indicate that chronic esophagltis may be involved in the natural history of esophageal carclnogenesis. Nutrient deficiencies may create an environment favorable to the development of precancerous lesions.展开更多
Gene therapy offers an elegant alternative to toxic chemotherapy regimens, mostly without severe side effects. Cancer gene therapy was among the first applications. Following the enthusiasm in the early nineties, a mo...Gene therapy offers an elegant alternative to toxic chemotherapy regimens, mostly without severe side effects. Cancer gene therapy was among the first applications. Following the enthusiasm in the early nineties, a more rationale view is the recent way to look at it. This tutorial review looks upon the tools of gene therapy and the principte elements （vector, promoter, targeting, therapeutic gene）. The principles of gene therapy such as gene directed enzyme prodrug therapy （GDEPT） and gene directed tumor vaccination are explained. Further, published protocols and clinical studies for pancreatic carcinoma gene therapy are reviewed. Finally, an outlook is given on the latest developments, some of them beyond conventional gene therapy.展开更多
In sub-Saharan Africa, breast cancer (BC) constitutes a serious public health problem and the genetic basis of its development is remaining poorly understood. Although the SNPs at codon 72 of <em>TP</em>53...In sub-Saharan Africa, breast cancer (BC) constitutes a serious public health problem and the genetic basis of its development is remaining poorly understood. Although the SNPs at codon 72 of <em>TP</em>53 (rs1042522) and at the UTR of <em>SET</em>8 (rs16917496) have both been associated with BC development among Asian and European women, no published data has been reported within African population. We herein report on the impact of these polymorphisms on the risk of BC among Cameroonian women. Blood samples were collected from 111 breast cancer patients and 224 controls. DNA was extracted from each sample and PCR-RFLP was used to investigate the polymorphisms at SNPs rs1042522 of <em>TP</em>53 and rs16917496 of <em>SET</em>8. Association studies were performed according to ethno-linguistic groups and menopausal status. The minor allele “T” of <em>SET</em>8 gene revealed a protective effect in premenopausal women (OR, 0.327;95% CI 0.125 - 0.852) while the CT genotype of <em>SET</em>8 was associated with increased risk of BC (OR, 2.93;95% CI, 1.1 - 7.8). The minor “G” allele of <em>TP</em>53 gene was significantly associated (OR, 2.533;95% CI, 1.455 - 4.408) with increased disease risk in premenopausal women while the CG genotype was significantly associated (OR, 0.39;95% CI, 0.23 - 0.69) with decreased risk of BC. A synergistic genetic interaction at both loci for CC genotype of SET8 and CG genotype of <em>TP</em>53 was associated (OR, 0.46;95% CI, 0.24 - 0.91) with reduced disease risk. No significant association between polymorphisms at the SET8 and <em>TP</em>53 loci and clinical pathologic features of BC was observed. This study suggests significant associations between the SNPs located at the 3’-UTR of <em>SET</em>8 and codon 72 of the <em>TP</em>53 with the risk of breast cancer development among premenopausal women. There is an interaction between <em>TP</em>53 and <em>SET</em>8 genes.展开更多
BACKGROUND Single-nucleotide polymorphisms(SNPs)of the serotonin type 3 receptor subunit(HTR3)genes have been associated with psychosomatic symptoms,but it is not clear whether these associations exist in irritable bo...BACKGROUND Single-nucleotide polymorphisms(SNPs)of the serotonin type 3 receptor subunit(HTR3)genes have been associated with psychosomatic symptoms,but it is not clear whether these associations exist in irritable bowel syndrome(IBS).AIM To assess the association of HTR3 polymorphisms with depressive,anxiety,and somatization symptoms in individuals with IBS.METHODS In this retrospective study,623 participants with IBS were recruited from five specialty centers in Germany,Sweden,the United States,the United Kingdom,and Ireland.Depressive,anxiety,and somatization symptoms and sociodemographic characteristics were collected.Four functional SNPs—HTR3A c.-42C>T,HTR3B c.386A>C,HTR3C c.489C>A,and HTR3E c.*76G>A—were genotyped and analyzed using the dominant and recessive models.We also performed separate analyses for sex and IBS subtypes.SNP scores were calculated as the number of minor alleles of the SNPs above.The impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx assays.RESULTS Depressive and anxiety symptoms significantly worsened with increasing numbers of minor HTR3C c.489C>A alleles in the dominant model(F_(depressive)=7.475,P_(depressive)=0.006;F_(anxiety)=6.535,P_(anxiety)=0.011).A higher SNP score(range 0-6)was linked to a worsened depressive symptoms score(F=7.710,P-linear trend=0.006)in IBS.The potential relevance of the HTR3C SNP was corroborated,showing changes in the expression level of 5-HT3AC variant receptors.CONCLUSION We have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with IBS.The SNP score indicated that an increasing number of minor alleles is linked to the worsening of depressive symptoms in IBS.展开更多
Objective:To provide the most up-to-date data on the burden of malignant mesothelioma(MM)and the projections through 2029 in China.Methods:Data on patients diagnosed with MM from China during 1990-2019 were obtained f...Objective:To provide the most up-to-date data on the burden of malignant mesothelioma(MM)and the projections through 2029 in China.Methods:Data on patients diagnosed with MM from China during 1990-2019 were obtained from the Global Burden of Disease(GBD)2019 database,including annual cases and deaths data and age-standardized rates of incidence,mortality,and disability-adjusted life-years(DALYs)associated with MM among different age groups.Temporal trends during 1990-2019 were analyzed by the Joinpoint regression models using 95%confidence interval(CI),while the projections through 2029 were calculated by the Bayesian age-period-cohort model.Data on the production and consumption of asbestos in China were obtained from the United States Geological Survey on Mineral Commodity Summaries during 1996-2023.Results:We observed a significant elevation in incident new cases and deaths over the last 3 decades,increasing from 1193 in 1990 to 2815 in 2019 for incident cases and from 1134 in 1990 to 2773 in 2019 for death cases.We found a roughly 6%increase in the proportion of incident cases for those aged>70 years(30%in 2019 versus 24%in 1990),while for the proportion of deaths similar elevation for those aged>70 years was found.Additionally,men had significantly higher DALYs due to MM across age groups compared with women.Asbestos consumption in China dramatically dropped since 2012 and reached the bottom in 2017 with 230 kilotons.By 2029,the projected age-standardized rate for incidence and mortality is expected to reach 1.2 per million for both.Conclusion:We found,for the first time using GBD data on the Chinese population,that the burden of MM has been significantly increasing in China over the last three decades and will continue to increase in the upcoming decade,suggesting an urgent need for a complete ban on chrysotile asbestos in China.展开更多
Cancers of the digestive system are major contributors to global cancer-associated morbidity and mortality,accounting for 35%of annual cases of cancer deaths.The etiologies,molecular features,and therapeutic managemen...Cancers of the digestive system are major contributors to global cancer-associated morbidity and mortality,accounting for 35%of annual cases of cancer deaths.The etiologies,molecular features,and therapeutic management of these cancer entities are highly heterogeneous and complex.Over the last decade,genomic and functional studies have provided unprecedented insights into the biology of digestive cancers,identifying genetic drivers of tumor progression and key interaction points of tumor cells with the immune system.This knowledge is continuously translated into novel treatment concepts and targets,which are dynamically reshaping the therapeutic landscape of these tumors.In this review,we provide a concise overview of the etiology and molecular pathology of the six most common cancers of the digestive system,including esophageal,gastric,biliary tract,pancreatic,hepatocellular,and colorectal cancers.We comprehensively describe the current stage-dependent pharmacological management of these malignancies,including chemo-,targeted,and immunotherapy.For each cancer entity,we provide an overview of recent therapeutic advancements and research progress.Finally,we describe how novel insights into tumor heterogeneity and immune evasion deepen our understanding of therapy resistance and provide an outlook on innovative therapeutic strategies that will shape the future management of digestive cancers,including CAR-T cell therapy,novel antibody-drug conjugates and targeted therapies.展开更多
Based on intriguing findings from observational studies[1,2],colonoscopy has since long been recommended for colorectal cancer(CRC)screening,long before evidence on its effectiveness in reducing CRC incidence and mort...Based on intriguing findings from observational studies[1,2],colonoscopy has since long been recommended for colorectal cancer(CRC)screening,long before evidence on its effectiveness in reducing CRC incidence and mortality was demonstrated by a randomized controlled trial(RCT).Such evidence has only recently been provided by the Nordic-European Initiative on Colorectal Cancer(NordICC)trial[3].In this RCT,the risk of CRC was lower among those invited to undergo screening colonoscopy than among those not invited to screening.However,reported CRC risk reduction was smaller than anticipated:The authors derived risk ratios of 0.82(95%confidence interval[CI]=0.70-0.93)and 0.69(95%CI=0.55-0.83)in intention-to-screen analysis and adjusted per-protocol analysis,respectively,suggesting an 18%risk reduction of CRC among those invited for screening and a 31%risk reduction among screening attenders.展开更多
文摘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.
基金supported by an intramural proof of concept grant of the NCT Heidelberg.
文摘Background The potential of exercise as a concurrent therapy for actively treated primary tumors has been suggested by emerging preclinical and observational studies.However,clinical trials regarding this question are scarce.Therefore,we conducted a randomized controlled trial investigating the effects of aerobic or resistance exercise concomitant to neoadjuvant chemotherapy(NACT)on tumor size.Methods In the BENEFIT study(German title:Bewegung bei neoadjuvanter chemotherapie zur verbesserung der fitness),patients with breast cancer scheduled for NACT were randomly assigned to supervised resistance training(RT,n=60)or aerobic training(AT,n=60)twice weekly during NACT or to a waitlist control group(WCG,n=60).The primary outcome,“change in tumor size”,as well as the secondary clinical outcomes pathologic complete response(pCR),type of surgery(breast conserving/mastectomy),axillary lymph node dissection(ALND,yes/no),premature discontinuation of chemotherapy(yes/no),and relative dose intensity(RDI)were derived from clinical records.Due to the highly skewed distribution,the primary outcome was categorized.Multiple(ordinal)logistic regression analyses were performed.Results Overall,there was no significant difference in post-intervention tumor size between RT or AT and WCG.However,there was a significant effect modification by hormone receptor(HR)status(P_(interaction)=0.030).Among patients with HR+tumors,results suggest a beneficial effect of AT on tumor shrinkage(odds ratio(OR)=2.37,95%confidence interval(95%CI):0.97‒5.78),on pCR(OR=3.21,95%CI:0.97‒10.61);and on ALND(OR=3.76,95%CI:0.78‒18.06)compared to WCG.The effects of RT were slightly less pronounced.For HR−subtypes,beneficial effects on RDI were found for AT(OR=3.71,95%CI:1.20‒11.50)and similarly for RT(OR=2.58,95%CI:0.88‒7.59).Both AT and RT had favorable effects on premature discontinuation of chemotherapy(OR(no vs.yes)=2.34,95%CI:1.10‒5.06),irrespective of tumor receptor status.Conclusion While there was no significant effect on the primary outcome in the overall group,aerobic and resistance exercise concomitant to NACT seem to beneficially affect tumor shrinkage and pCR,reduce the need for ALND among patients with HR+breast cancers,and prevent low RDI among patients with HR–breast cancers.These results warrant confirmation in further trials.
基金Supported by Zentrum für Geriatrische Onkologie und Biologie in der Metropolregion Rhein Neckar(ZOBEL)
文摘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.
文摘Lung cancer is the most common cancer type worldwide and has the highest and second highest mortality rate for men and women respectively in Germany.Yet,the role of comorbid illnesses in lung cancer patient prognosis is still debated.We analyzed administrative claims data from one of the largest statutory health insurance(SHI)funds in Germany,covering close to 9 million people(11%of the national population);observation period was from 2005 to 2019.Lung cancer patients and their concomitant diseases were identified by ICD-10-GM codes.Comorbidities were classified according to the Charlson Comorbidity Index(CCI).Incidence,comorbidity prevalence and survival are estimated considering sex,age at diagnosis,and place of residence.Kaplan Meier curves with 95%confidence intervals were built in relation to common comorbidities.We identified 70,698 lung cancer incident cases in the sample.Incidence and survival figures are comparable to official statistics in Germany.Most prevalent comorbidities are chronic obstructive pulmonary disease(COPD)(36.7%),followed by peripheral vascular disease(PVD)(18.7%),diabetes without chronic complications(17.4%),congestive heart failure(CHF)(16.5%)and renal disease(14.7%).Relative to overall survival,lung cancer patients with CHF,cerebrovascular disease(CEVD)and renal disease are associated with largest drops in survival probabilities(9%or higher),while those with PVD and diabetes without chronic complications with moderate drops(7%or lower).The study showed a negative association between survival and most common comorbidities among lung cancer patients,based on a large sample for Germany.Further research needs to explore the individual effect of comorbidities disentangled from that of other patient characteristics such as cancer stage and histology.
文摘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.
基金supported by the Hospital Partnerships by Germany's Federal Ministry of Economic Cooperation and Development(BMZ)the Else Kroner-Fresenius-Stiftung and the Foundation Wienbeck,Germany.
文摘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.
文摘AIM:To investigate biological prevention with flavonoids the recurrence risk of neoplasia was studied in patients with resected colorectal cancer and after adenoma polypectomy.METHODS:Eighty-seven patients,36 patients with resected colon cancer and 51 patients after polypectomy,were divided into 2 groups:one group was treated with a flavonoid mixture(daily standard dose 20 mg apigenin and 20 mg epigallocathechin-gallat,n=31)and compared with a matched control group(n=56).Both groups were observed for 3-4 years by surveillance colonoscopy and by questionnaire.RESULTS:Of 87 patients enrolled in this study,36 had resected colon cancer and 29 of these patients had surveillance colonoscopy.Among the flavonoid-treated patients with resected colon cancer(n=14),there was no cancer recurrence and one adenoma developed.In contrast the cancer recurrence rate of the 15 matched untreated controls was 20%(3 of 15)and adenomas evolved in 4 of those patients(27%).The combined recurrence rate for neoplasia was 7%(1 of 14)in the treated patients and 47%(7 of 15)in the controls(P=0.027).CONCLUSION:Sustained long-term treatment with a flavonoid mixture could reduce the recurrence rate of colon neoplasia in patients with resected colon cancer.
基金supported by a CRI Lloyd J. Old STAR Award(Grant No. 3914)a Helmholtz Young Investigator Award(Grant No. VH-NG-1113)+7 种基金an EMBO Young Investigator Awardan Exploration Grant of the Boehringer Ingelheim Foundation (BIS)the German Research Foundation (DFG,Grant Nos. CU375/5-1, CU375/5-2, CU375/7-1, CU375/9-1, and 259332240/RTG2099)the German Cancer Aid Foundation (DKH, Grant Nos. 70113343 and 70114224)the Helmholtz Zukunftsthema Ageing and Metabolic Programming (AMPro, Grant No. ZT0026)HI-TRON KickStart Seed Funding (Grant No. HITR-2021-08)the Hector Foundation (Grant No. M20102)an ERC Consolidator Award (Grant No. 101045416)
文摘The tumor microenvironment is an ecosystem composed of multiple types of cells, such as tumor cells, immune cells, and cancerassociated fibroblasts. Cancer cells grow faster than non-cancerous cells and consume larger amounts of nutrients. The rapid growth characteristic of cancer cells fundamentally alters nutrient availability in the tumor microenvironment and results in reprogramming of immune cell metabolic pathways. Accumulating evidence suggests that cellular metabolism of nutrients, such as lipids and amino acids, beyond being essential to meet the bioenergetic and biosynthetic demands of immune cells, also regulates a broad spectrum of cellular signal transduction, and influences immune cell survival, differentiation, and anti-tumor effector function. The cancer immunometabolism research field is rapidly evolving, and exciting new discoveries are reported in high-profile journals nearly weekly. Therefore, all new findings in this field cannot be summarized within this short review. Instead, this review is intended to provide a brief introduction to this rapidly developing research field, with a focus on the metabolism of two classes of important nutrients-lipids and amino acids-in immune cells. We highlight recent research on the roles of lipids and amino acids in regulating the metabolic fitness and immunological functions of T cells, macrophages, and natural killer cells in the tumor microenvironment. Furthermore, we discuss the possibility of “editing” metabolic pathways in immune cells to act synergistically with currently available immunotherapies in enhancing anti-tumor immune responses.
基金supported by the German Cancer Aid Foundation (Deutsche Krebshilfe, Grant Nos. 70112835, 70113510 and 70114428 to nNGM)the Hector Foundation Ⅱ to SL
文摘Lung cancer remains the leading cause of cancer-associated mortality worldwide,but with the emergence of oncogene targeted therapies,treatment options have tremendously improved.Owing to their biological relevance,members of the ERBB receptor family,including the EGF receptor(EGFR),HER2,HER3 and HER4,are among the best studied oncogenic drivers.Activating EGFR mutations are frequently observed in non-small cell lung cancer(NSCLC),and small molecule tyrosine kinase inhibitors(TKIs)are the established first line treatment option for patients whose tumors bear"typical/classical"EGFR mutations(exon 19 deletions,L858R point mutations).Additionally,new TKIs are rapidly evolving with better efficacy to overcome primary and secondary treatment resistance(e.g.,that due to T790M or C797S resistance mutations).Some atypical EGFR mutations,such as the most frequent exon 20 insertions,exhibit relative resistance to earlier generation TKIs through steric hindrance.In this subgroup,newer TKIs,such as mobocertinib and the bi-specific antibody amivantamab have recently been approved,whereas less frequent atypical EGFR mutations remain understudied.In contrast to EGFR,HER2 has long remained a challenging target,but better structural understanding has led to the development of newer generations of TKIs.The recent FDA approval of the antibody-drug conjugate trastuzumab-deruxtecan for pretreated patients with HER2 mutant NSCLC has been an important therapeutic breakthrough.HER3 and HER4 also exert oncogenic potential,and targeted treatment approaches are being developed,particularly for HER3.Overall,strategies to inhibit the oncogenic function of ERBB receptors in NSCLC are currently evolving at an unprecedented pace;therefore,this review summarizes current treatment standards and discusses the outlook for future developments.
基金A Research Grant of Merck Pharma GmbH,Darmstadt,Germany,to the University Clinic of Mainz
文摘AIM： TO explore the role of Bcl-XL and Myeloid cell leukaemia （Mcl）-I for the apoptosis resistance of colorectal carcinoma （CRC） cells towards current treatment modalities. METHODS： Bcl-XL and Mcl-1 mRNA and protein expression were analyzed in CRC cell lines as well as human CRC tissue by Western blot, quantitative PCRand immunohistochemistry. Bcl-XL and Mcl-1 protein expression was knocked down or increased in CRC cell lines by applying specific siRNAs or expression plasmids, respectively. After modulation of protein expression, CRC cells were treated with chemotherapeutic agents, an antagonistic epidermal growth factor receptor （EGFR1） antibody, an EGFR1 tyrosine kinase inhibitor, or with the death receptor ligand TRAIL. Apoptosis induction and cell viability were analyzed. RESULTS： Here we show that in human CRC tissue and various CRC cell lines both Bcl-xL and Mcl-1 are expressed. Bcl-xL expression was higher in CRC tissue than in surrounding non-malignant tissue, both on protein and mRNA level. Mcl-1 mRNA expression was significantly lower in malignant tissues. However, protein expression was slightly higher. Viability rates of CRC cells were significantly decreased after knock down of Bcl-xL expression, and, to a lower extent, after knock down of Mcl-1 expression. Furthermore, cells with reduced Bcl-xL or Mcl-1 expression was more sensitive towards oxaliplatinand irinotecan-induced apoptosis, and in the case of Bcl-xL also towards 5-FU-induced apoptosis. On the other hand, upregulation of Bcl-xL by transfection of an expression plasmid decreased chemotherapeutic drug-induced apoptosis. EGF treatment clearly induced Bcl-xL and Mcl-1 expression in CRC cells. Apoptosis induction upon EGFR1 blockage by cetuximab or PD168393 was increased by inhibiting Mcl-1 and Bcl-xL expression. More strikingly, CD95- and TRAIL-induced apoptosis was increased by Bcl-xL knock down. CONCLUSION： Our data suggest that Bcl-xL and, to a lower extent, Mcl-1, are important anti-apoptotic factors in CRC. Specific downregulation of Bcl-xL is a promising approach to sensitize CRC cells towards chemotherapy and targeted therapy.
基金supported by the Guangzhou Elite Project (GEP)supported by grants from the German Research Council (Grant Nos. BR 1704/6-1, BR1704/6-3, BR 1704/6-4, BR 1704/6-6, CH 117/1-1, and BR 1704/17-1, HO 5117/2-1)the German Federal Ministry of Education and Research (Grant Nos. 01KH0404, 01ER0814, 01ER0815, and 01GL1712)
文摘Objective:We aimed to directly compare the estimated effects of adherence to a healthy lifestyle with those of risk predisposition according to known genetic variants affecting colorectal cancer(CRC)risk,to support effective risk communication for cancer prevention.Methods:A healthy lifestyle score(HLS)was derived from 5 lifestyle factors:smoking,alcohol consumption,diet,physical activity,and body adiposity.The association of lifestyle and polygenic risk score(PRS)(based on 140 CRC-associated risk loci)with CRC risk was assessed with multiple logistic regression and compared through the genetic risk equivalent(GRE),a novel approach providing an estimate of the effects of adherence to a healthy lifestyle in terms of percentile differences in PRS.Results:A higher HLS was associated with lower CRC risk(4,844 cases,3,964 controls).Those adhering to all 5 healthy lifestyle factors had a 62%(95%CI 54%-68%)lower CRC risk than those adhering to≤2 healthy lifestyle factors.The estimated effect of adherence to all 5 compared with≤2 healthy lifestyle factors was as strong as the effect of having a 79 percentile(GRE 79,95%CI 61-97)lower PRS.The association between a healthy lifestyle and CRC risk was independent of PRS level but was particularly pronounced among those with a family history of CRC in≥1 first-degree relative(P-interaction=0.0013).Conclusions:A healthy lifestyle was strongly inversely associated with CRC risk.The large GRE indicated that CRC risk determined by polygenic risk may be offset to a substantial extent by adherence to a healthy lifestyle.
文摘Pancreatic cancer has a considerably poor prognosis with a 5-year survival probability of less than 5% when all stages are combined. Pancreatic cancer is characterized by its dense stroma, which is involved in the critical interplay with the tumor cells throughout tumor progression and furthermore, creates a barrier restricting efficient penetration of therapeutics. Alterations in a large number of genes are reflected by a limited number of signaling pathways, which are potential targets. Understanding more about the molecular basis of this devastating cancer type regarding tumor microenvironment, distinct subpopulations of cells, epithelial-to-mesenchymal transition and inflammation will lead to the development of various targeted therapies for controlling tumor growth and metastasis. In this complex scenario of pancreatic cancer, especially members of the “small integrin binding ligand N-linked glycoproteins” (SIBLINGs) and “secreted protein acidic and rich in cysteine” (SPARC) families have emerged due to their prominent roles in properties including proliferation, differentiation, apoptosis, adhesion, migration, angiogenesis, wound repair and regulation of extracellular matrix remodeling. SIBLINGs consist of five members, which include osteopontin (OPN), bone sialoprotein, dentin matrix protein 1, dentin sialophosphoprotein and matrix extracellular phosphoglycoprotein. The SPARC family of modular extracellular proteins is comprised of SPARC/osteonectin (ON) and SPARC-like 1 (hevin); secreted modular calcium binding proteins; testicans and follistatin-like protein. In this review, we especially focus on OPN and ON, elaborating on their special and growing importance in pancreatic cancer diagnosis and prognosis.
文摘This review summarizes the current status of neoadjuvantradiation approaches in the treatment of pancreatic cancer,including a description of modern radiation techniques,and an overview on the literature regarding neoadjuvantradio- or radiochemotherapeutic strategies both forresectable and irresectable pancreatic cancer. Neoadjuvantchemoradiation for locally-advanced, primarily non- orborderline resectable pancreas cancer results in secondaryresectability in a substantial proportion of patients withconsecutively markedly improved overall prognosisand should be considered as possible alternative inpretreatment multidisciplinary evaluations. In resectablepancreatic cancer, outstanding results in terms ofresponse, local control and overall survival have beenobserved with neoadjuvant radio- or radiochemotherapy inseveral phase Ⅰ/Ⅱ trials, which justify further evaluationof this strategy. Further investigation of neoadjuvantchemoradiation strategies should be performed preferentiallyin randomized trials in order to improvecomparability of the current results with other treatmentmodalities. This should include the evaluation of optimalsequencing with newer and more potent systemicinduction therapy approaches. Advances in patientselection based on new molecular markers might be ofcrucial interest in this context. Finally modern externalbeam radiation techniques (intensity-modulated radiationtherapy, image-guided radiation therapy and stereotacticbody radiation therapy), new radiation qualities (protons,heavy ions) or combinations with alternative boostingtechniques widen the therapeutic window and contributeto the reduction of toxicity.
文摘This paper reports the prevalence of chronic esophagitis and nutritional status among 538 young persons aged 15 to 26 years from the high risk area for esophageal cancer. Of these subjects, 166 were from households with history of esophageal cancer and 372 were from households without history of esophageal cancer. The Incidences of chronic esophagltis among male and female adolescents were 37. 6% and 36% respectively, which was significantly higher than those in the low risk area (17%). The frequency of chronic esophagltis in the adolescents in the households with history of esophageal cancer was aiso higher than in those In the households without history of esophageal cancer. The deficiencies of vitamins, especially of riboflavin and ascorbate, are prevalent and severe among these adolescents. Ascorbate deficiency Is correlated with the severity of the chronic esophagltis. These results indicate that chronic esophagltis may be involved in the natural history of esophageal carclnogenesis. Nutrient deficiencies may create an environment favorable to the development of precancerous lesions.
文摘Gene therapy offers an elegant alternative to toxic chemotherapy regimens, mostly without severe side effects. Cancer gene therapy was among the first applications. Following the enthusiasm in the early nineties, a more rationale view is the recent way to look at it. This tutorial review looks upon the tools of gene therapy and the principte elements （vector, promoter, targeting, therapeutic gene）. The principles of gene therapy such as gene directed enzyme prodrug therapy （GDEPT） and gene directed tumor vaccination are explained. Further, published protocols and clinical studies for pancreatic carcinoma gene therapy are reviewed. Finally, an outlook is given on the latest developments, some of them beyond conventional gene therapy.
文摘In sub-Saharan Africa, breast cancer (BC) constitutes a serious public health problem and the genetic basis of its development is remaining poorly understood. Although the SNPs at codon 72 of <em>TP</em>53 (rs1042522) and at the UTR of <em>SET</em>8 (rs16917496) have both been associated with BC development among Asian and European women, no published data has been reported within African population. We herein report on the impact of these polymorphisms on the risk of BC among Cameroonian women. Blood samples were collected from 111 breast cancer patients and 224 controls. DNA was extracted from each sample and PCR-RFLP was used to investigate the polymorphisms at SNPs rs1042522 of <em>TP</em>53 and rs16917496 of <em>SET</em>8. Association studies were performed according to ethno-linguistic groups and menopausal status. The minor allele “T” of <em>SET</em>8 gene revealed a protective effect in premenopausal women (OR, 0.327;95% CI 0.125 - 0.852) while the CT genotype of <em>SET</em>8 was associated with increased risk of BC (OR, 2.93;95% CI, 1.1 - 7.8). The minor “G” allele of <em>TP</em>53 gene was significantly associated (OR, 2.533;95% CI, 1.455 - 4.408) with increased disease risk in premenopausal women while the CG genotype was significantly associated (OR, 0.39;95% CI, 0.23 - 0.69) with decreased risk of BC. A synergistic genetic interaction at both loci for CC genotype of SET8 and CG genotype of <em>TP</em>53 was associated (OR, 0.46;95% CI, 0.24 - 0.91) with reduced disease risk. No significant association between polymorphisms at the SET8 and <em>TP</em>53 loci and clinical pathologic features of BC was observed. This study suggests significant associations between the SNPs located at the 3’-UTR of <em>SET</em>8 and codon 72 of the <em>TP</em>53 with the risk of breast cancer development among premenopausal women. There is an interaction between <em>TP</em>53 and <em>SET</em>8 genes.
基金results in part from collaboration and network activities promoted under the frame of the international network GENIEUR (Genes in Irritable Bowel Syndrome Research Network Europe),which has been funded by the COST program (BM1106, www.GENIEUR.eu)currently supported by the European Society of Neurogastroenterology and Motility (ESNM, www.ESNM.eu)
文摘BACKGROUND Single-nucleotide polymorphisms(SNPs)of the serotonin type 3 receptor subunit(HTR3)genes have been associated with psychosomatic symptoms,but it is not clear whether these associations exist in irritable bowel syndrome(IBS).AIM To assess the association of HTR3 polymorphisms with depressive,anxiety,and somatization symptoms in individuals with IBS.METHODS In this retrospective study,623 participants with IBS were recruited from five specialty centers in Germany,Sweden,the United States,the United Kingdom,and Ireland.Depressive,anxiety,and somatization symptoms and sociodemographic characteristics were collected.Four functional SNPs—HTR3A c.-42C>T,HTR3B c.386A>C,HTR3C c.489C>A,and HTR3E c.*76G>A—were genotyped and analyzed using the dominant and recessive models.We also performed separate analyses for sex and IBS subtypes.SNP scores were calculated as the number of minor alleles of the SNPs above.The impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx assays.RESULTS Depressive and anxiety symptoms significantly worsened with increasing numbers of minor HTR3C c.489C>A alleles in the dominant model(F_(depressive)=7.475,P_(depressive)=0.006;F_(anxiety)=6.535,P_(anxiety)=0.011).A higher SNP score(range 0-6)was linked to a worsened depressive symptoms score(F=7.710,P-linear trend=0.006)in IBS.The potential relevance of the HTR3C SNP was corroborated,showing changes in the expression level of 5-HT3AC variant receptors.CONCLUSION We have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with IBS.The SNP score indicated that an increasing number of minor alleles is linked to the worsening of depressive symptoms in IBS.
基金supported by grants from Zhejiang Provincial Ten-Thousand Talents Plan(grant number:2021R52020)the Horizon 2020 Program of the European Union(grant number:856620).
文摘Objective:To provide the most up-to-date data on the burden of malignant mesothelioma(MM)and the projections through 2029 in China.Methods:Data on patients diagnosed with MM from China during 1990-2019 were obtained from the Global Burden of Disease(GBD)2019 database,including annual cases and deaths data and age-standardized rates of incidence,mortality,and disability-adjusted life-years(DALYs)associated with MM among different age groups.Temporal trends during 1990-2019 were analyzed by the Joinpoint regression models using 95%confidence interval(CI),while the projections through 2029 were calculated by the Bayesian age-period-cohort model.Data on the production and consumption of asbestos in China were obtained from the United States Geological Survey on Mineral Commodity Summaries during 1996-2023.Results:We observed a significant elevation in incident new cases and deaths over the last 3 decades,increasing from 1193 in 1990 to 2815 in 2019 for incident cases and from 1134 in 1990 to 2773 in 2019 for death cases.We found a roughly 6%increase in the proportion of incident cases for those aged>70 years(30%in 2019 versus 24%in 1990),while for the proportion of deaths similar elevation for those aged>70 years was found.Additionally,men had significantly higher DALYs due to MM across age groups compared with women.Asbestos consumption in China dramatically dropped since 2012 and reached the bottom in 2017 with 230 kilotons.By 2029,the projected age-standardized rate for incidence and mortality is expected to reach 1.2 per million for both.Conclusion:We found,for the first time using GBD data on the Chinese population,that the burden of MM has been significantly increasing in China over the last three decades and will continue to increase in the upcoming decade,suggesting an urgent need for a complete ban on chrysotile asbestos in China.
基金supported by DFG-SFB1324.MPE is supported by the DFG(RTG 2727,Project B1.3.,445549683)the Dr.Hans und Lore Graf Stiftung,Germany.JB is supported by the Hector Foundation II.ML and LD were supported by the Clinician Scientist Program ICON of the Medical Faculty Mannheim.We apologize to all colleagues whose work was not cited due to space constraints.
文摘Cancers of the digestive system are major contributors to global cancer-associated morbidity and mortality,accounting for 35%of annual cases of cancer deaths.The etiologies,molecular features,and therapeutic management of these cancer entities are highly heterogeneous and complex.Over the last decade,genomic and functional studies have provided unprecedented insights into the biology of digestive cancers,identifying genetic drivers of tumor progression and key interaction points of tumor cells with the immune system.This knowledge is continuously translated into novel treatment concepts and targets,which are dynamically reshaping the therapeutic landscape of these tumors.In this review,we provide a concise overview of the etiology and molecular pathology of the six most common cancers of the digestive system,including esophageal,gastric,biliary tract,pancreatic,hepatocellular,and colorectal cancers.We comprehensively describe the current stage-dependent pharmacological management of these malignancies,including chemo-,targeted,and immunotherapy.For each cancer entity,we provide an overview of recent therapeutic advancements and research progress.Finally,we describe how novel insights into tumor heterogeneity and immune evasion deepen our understanding of therapy resistance and provide an outlook on innovative therapeutic strategies that will shape the future management of digestive cancers,including CAR-T cell therapy,novel antibody-drug conjugates and targeted therapies.
基金supported in part by grants from the German Federal Ministry of Education and Research(grant no.01KD2104A)the German Cancer Aid(grant no.70114735).
文摘Based on intriguing findings from observational studies[1,2],colonoscopy has since long been recommended for colorectal cancer(CRC)screening,long before evidence on its effectiveness in reducing CRC incidence and mortality was demonstrated by a randomized controlled trial(RCT).Such evidence has only recently been provided by the Nordic-European Initiative on Colorectal Cancer(NordICC)trial[3].In this RCT,the risk of CRC was lower among those invited to undergo screening colonoscopy than among those not invited to screening.However,reported CRC risk reduction was smaller than anticipated:The authors derived risk ratios of 0.82(95%confidence interval[CI]=0.70-0.93)and 0.69(95%CI=0.55-0.83)in intention-to-screen analysis and adjusted per-protocol analysis,respectively,suggesting an 18%risk reduction of CRC among those invited for screening and a 31%risk reduction among screening attenders.
