Diabetes mellitus(DM)comprises distinct subtypes-including type 1 DM,type 2 DM,and gestational DM-all characterized by chronic hyperglycemia and sub-stantial morbidity.Conventional diagnostic and therapeutic strategie...Diabetes mellitus(DM)comprises distinct subtypes-including type 1 DM,type 2 DM,and gestational DM-all characterized by chronic hyperglycemia and sub-stantial morbidity.Conventional diagnostic and therapeutic strategies often fall short in addressing the complex,multifactorial nature of DM.This review ex-plores how multi-omics integration enhances our mechanistic understanding of DM and informs emerging personalized therapeutic approaches.We consolidated genomic,transcriptomic,proteomic,metabolomic,and microbiomic data from major databases and peer-reviewed publications(2015-2025),with an emphasis on clinical relevance.Multi-omics investigations have identified convergent mole-cular networks underlyingβ-cell dysfunction,insulin resistance,and diabetic complications.The combination of metabolomics and microbiomics highlights critical interactions between metabolic intermediates and gut dysbiosis.Novel biomarkers facilitate early detection of DM and its complications,while single-cell multi-omics and machine learning further refine risk stratification.By dissecting DM heterogeneity more precisely,multi-omics integration enables targeted in-terventions and preventive strategies.Future efforts should focus on data har-monization,ethical considerations,and real-world validation to fully leverage multi-omics in addressing the global DM burden.展开更多
Colorectal cancer(CRC)is one of the most commonly diagnosed cancers worldwide and 30%of patients with CRC experience metastasis.Patients with metastatic colorectal cancer(mCRC)have a 5-year overall survival rate of<...Colorectal cancer(CRC)is one of the most commonly diagnosed cancers worldwide and 30%of patients with CRC experience metastasis.Patients with metastatic colorectal cancer(mCRC)have a 5-year overall survival rate of<10%.V-raf murine sarcoma viral oncogene homolog B1(BRAF)and V-Ki-ras2 Kirsten ratsarcoma viral oncogene homolog(KRAS)mutations are mostly studied in mCRC,as clinical trials found that first-line chemotherapy with anti-epidermal growth factor receptor agent confers limited efficacy for mCRC.Treatment decisions for early-stage mCRC do not consider BRAF or KRAS mutations,given the dramatically poor prognosis conferred by these mutations in clinical trials.Thus,it is necessary to identify patients with mCRC harboring BRAF or KRAS mutations to formulate rational therapeutic strategies to improve prognosis and survival.BRAF and KRAS mutations occur in10%and44%of patients with mCRC,respectively.Although the survival rate of patients with mCRC has improved in recent years,the response and prognosis of patients with the aforementioned mutations are still poor.There is a substantial unmet need for prospective personalized therapies for patients with BRAF-or KRAS-mutant mCRC.In this review,we focus on BRAF and KRAS mutations to understand the mechanisms underlying resistance and improving the response rate,outcomes,and prognosis of patients with mCRC bearing these mutations and to discuss prospective personalized therapies for BRAF-and KRAS-mutant mCRC.展开更多
Diabetes mellitus （DM） is one of the most common ＇metabolic disorders in the world~ in which more than90% are grouped to type 2 DM （T2DM）.1 T2DM is characterized by decreased insulin sensitivity and impaired insu...Diabetes mellitus （DM） is one of the most common ＇metabolic disorders in the world~ in which more than90% are grouped to type 2 DM （T2DM）.1 T2DM is characterized by decreased insulin sensitivity and impaired insulin secretion2 leading to hyperglycemia, and the serum glucose has been used as a golden standard for diabetes diagnosis. However, T2DM is a kind of disease involving defects of multiple organs, which cannot be distinguished through the measurement of the serum-glucose level. In addition, T2DM is a multiple-stage disease, which usually covers several decades from impaired plasma glucose to various complications. The serum-glucose level only reflects the consequence of multiole physiological disorders in the Riven stare.展开更多
We previously demonstrated that gene-modified umbilical cord blood mononuclear cells overexpressing a combination of recombinant neurotrophic factors are a promising therapeutic approach for cell-mediated gene therapy...We previously demonstrated that gene-modified umbilical cord blood mononuclear cells overexpressing a combination of recombinant neurotrophic factors are a promising therapeutic approach for cell-mediated gene therapy for neurodegenerative diseases,neurotrauma,and stroke.In this study,using a mini pig model of spinal cord injury,we proposed for the first time the use of gene-modified leucoconcentrate prepared from peripheral blood in the plastic blood bag for personalized ex vivo gene therapy.Leucoconcentrate obtained from mini pig peripheral blood was transduced with a chimeric adenoviral vector(Ad5/35 F)that carried an enhanced green fluorescent protein(EGFP)reporter gene in the plastic blood bag.The day after blood donation,the mini pigs were subjected to moderate SCI and four hours post-surgery they were intravenously autoinfused with gene-modified leucoconcentrate.A week after gene-modified leucoconcentrate therapy,fluorescent microscopy revealed EGFP-expressing leucocytes in spinal cord at the site of contusion injury.In the spleen the groups of EGFP-positive cells located in the lymphoid follicles were observed.In vitro flow cytometry and fluorescent microscopy studies of the gene-modified leucoconcentrate samples also confirmed the production of EGFP by leucocytes.Thus,the efficacy of leucocytes transduction in the plastic blood bag and their migratory potential suggest their use for temporary production of recombinant biologically active molecules to correct certain pathological conditions.This paper presents a proof-of-concept of simple,safe and effective approach for personalized ex vivo gene therapy based on gene-modified leucoconcentrate autoinfusion.The animal protocols were approved by the Kazan State Medical University Animal Care and Use Committee(approval No.5)on May 27,2014.展开更多
Keloids,which are abnormal manifestations of wound healing,can result in significant functional impairment and aesthetic deformities.The pathogenesis of keloids is multifaceted and complex and influenced by various fa...Keloids,which are abnormal manifestations of wound healing,can result in significant functional impairment and aesthetic deformities.The pathogenesis of keloids is multifaceted and complex and influenced by various factors,such as genetics,the environment,and immune responses.The evolution of keloid treatment has progressed from traditional surgical excision to a contemporary combination of therapies including injection and radiation treatments,among others.This article provides a comprehensive review of keloid pathogenesis and treatment,emphasizing the latest advances in the field.Ultimately,this review underscores the necessity for continued research to enhance our understanding of keloid pathogenesis and to devise more effective treatments for this challenging condition.展开更多
Laryngeal squamous cell carcinoma(LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for L...Laryngeal squamous cell carcinoma(LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for LSCC has stagnated over the past few decades. As the era of next-generation sequencing and personalized treatment for cancer approaches, LSCC may be an ideal disease for consideration of further treatment stratification and personalization. Here, we will discuss the important history of LSCC as a model system for organ preservation, unique and potentially targetable genetic signatures of LSCC, and methods for bringing stratified, personalized treatment strategies to the 21^(st) century.展开更多
The management of breast cancer,one of the most common and heterogeneous malignancies,has transformed with the advent of precision medicine.This review explores current developments in genetic profiling,molecular diag...The management of breast cancer,one of the most common and heterogeneous malignancies,has transformed with the advent of precision medicine.This review explores current developments in genetic profiling,molecular diagnostics,and targeted therapies that have revolutionized breast cancer treatment.Key innovations,such as cyclin-dependent kinases 4/6(CDK4/6)inhibitors,antibodydrug conjugates(ADCs),and immune checkpoint inhibitors(ICIs),have improved outcomes for hormone receptor-positive(HR+),HER2-positive(HER2+),and triple-negative breast cancer(TNBC)subtypes remarkably.Additionally,emerging treatments,such as PI3K inhibitors,poly(ADP-ribose)polymerase(PARP)inhibitors,and m RNA-based therapies,offer new avenues for targeting specific genetic mutations and improving treatment response,particularly in difficult-to-treat breast cancer subtypes.The integration of liquid biopsy technologies provides a non-invasive approach for real-time monitoring of tumor evolution and treatment response,thus enabling dynamic adjustments to therapy.Molecular imaging and artificial intelligence(AI)are increasingly crucial in enhancing diagnostic precision,personalizing treatment plans,and predicting therapeutic outcomes.As precision medicine continues to evolve,it has the potential to significantly improve survival rates,decrease recurrence,and enhance quality of life for patients with breast cancer.By combining cutting-edge diagnostics,personalized therapies,and emerging treatments,precision medicine can transform breast cancer care by offering more effective,individualized,and less invasive treatment options.展开更多
In this editorial we comment on the article published in the recent issue of World Journal of Gastrointestinal Oncology.This study aims to explore the relationship be-tween preoperative inflammation markers and the re...In this editorial we comment on the article published in the recent issue of World Journal of Gastrointestinal Oncology.This study aims to explore the relationship be-tween preoperative inflammation markers and the recurrence of gastrointestinal stromal tumors(GIST)after surgery.It is well known that the best-documented prognostic parameters for GIST are mitotic activity,tumor size and anatomical site.Besides,mutation status represents a prognostic as well as predictive factor.This study provides a new tool for postoperative recurrence risk assessment of GIST patients by establishing a line chart prediction model,which is certificated by previous research that high platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio correlated with increased tumour sizes,more advanced tumour stages and mitotic index.However,as a retrospective study,inevitable bias exists in the results;furthermore,the sample size of this study is relatively small,in-fluencing the universality of the results.Moreover,when assessing risk rating and prognosis of GIST,some novel inflammatory makers could be taken into consi-deration,such as proenkephalin and SLITRK3.Overall,this study can offer an additional model for GIST prognosis and recurrence risk assessment,indepen-dent of the traditional prognostic factors of GIST.展开更多
In the unrelenting race to strive to dominate type 2 diabetes mellitus(T2DM)care better,this review paper sets out on a significant discovery trip across recent advancements in treatment and the blooming era of artifi...In the unrelenting race to strive to dominate type 2 diabetes mellitus(T2DM)care better,this review paper sets out on a significant discovery trip across recent advancements in treatment and the blooming era of artificial intelligence(AI)utilities.Given the considerable global burden of T2DM,innovative therapeutic approaches to improve patient outcomes remain a public health priority.This review first provides an in-depth analysis of the current state of therapy,from novel pharmacotherapy to lifestyle interventions and new treatment methods.At the same time,the rapidly increasing role of AI in diabetes care is woven into the story,mainly targeting how insulin therapy can be modified and personalized through algorithms and predictive modelling.It leaves a deep review of their pre-existing synergies,which helps understand how collaborative opportunities will unlock the future of T2DM care.This critical role is shown by integrating recent therapeutic advances and AI with overall showcasing better screening,diagnosis,and therapeutics decision-making to outcome prediction in T2DM.The review emphasizes how AI applications in insulin therapy have transformative potential in diabetes care.These person-centred approaches to T2DM management,which are more effective and personalized than some traditional strategies,only work because of the often-hidden synergies between AI algorithms in areas such as diagnostic criteria,predictive methods,and familiar classification tools for subgroups with relevant aspects/predictors on prognosis or treatment responsiveness.展开更多
Nocardiosis remains a rare and often underdiagnosed bacterial infection,particularly in immunocompromised individuals.The case report by Zhang et al highlights the diagnostic and therapeutic challenges in managing Noc...Nocardiosis remains a rare and often underdiagnosed bacterial infection,particularly in immunocompromised individuals.The case report by Zhang et al highlights the diagnostic and therapeutic challenges in managing Nocardia brasiliensis skin infection in a 93-year-old patient with chronic renal insufficiency.This editorial explores the importance of timely diagnosis,microbiological confirmation,and tailored antibiotic therapy.Emphasis is placed on the role of immune status evaluation,drug concentration monitoring,and the necessity of long-term antimicrobial therapy.Improved clinician awareness and adherence to evidencebased management protocols are essential to achieving better outcomes in nocardiosis cases.展开更多
Since its initial characterization, pancreatic ductal adenocarcinoma has remained one of the most devastating and difficult cancers to treat. Pancreatic cancer is the fourth leading cause of death in the United States...Since its initial characterization, pancreatic ductal adenocarcinoma has remained one of the most devastating and difficult cancers to treat. Pancreatic cancer is the fourth leading cause of death in the United States, resulting in an estimated 38460 deaths annually. With few screening tools available to detect this disease at an early stage, 94% of patients will die within five years of diagnosis. Despite decades of research that have led to a better understanding of the molecular and cellular signaling pathways in pancreatic cancer cells, few effective therapies have been developed to target these pathways. Other treatment options have included more sophisticated pancreatic cancer surgeries and combination therapies. While outcomes have improved modestly for these patients, more effective treatments are desperately needed. One of the greatest challenges in the future of treating this malignancy will be to develop therapies that target the tumor microenvironment and surrounding pancreatic cancer stem cells in addition to pancreatic cancer cells. Recent advances in targeting pancreatic stellate cells and the stroma have encouraged researchers to shift their focus to the role of desmoplasia in pancreatic cancer pathobiology in the hopes of developing newer-generation therapies. By combining novel agents with current cytotoxic chemotherapies and radiation therapy and personalizing them to each patient based on specific biomarkers, the goal of prolonging a patient’s life could be achieved. Here we review the most effective therapies that have been used for the treatment of pancreatic cancer and discuss the future potential of therapeutic options.展开更多
Gastric cancer(GC) is a highly aggressive and life-threatening malignancy.Even with radical surgical removal and front-line chemotherapy,more than half of GCs locally relapse and metastasize at a distant site.The dism...Gastric cancer(GC) is a highly aggressive and life-threatening malignancy.Even with radical surgical removal and front-line chemotherapy,more than half of GCs locally relapse and metastasize at a distant site.The dismal outcomes reflect the ineffectiveness of a one-size fits-all approach for a highly heterogeneous disease with diverse etiological causes and complex molecular underpinnings.The recent comprehensive genomic and molecular profiling has led to our deepened understanding of GC.The emerging molecular classification schemes based on the genetic,epigenetic,and molecular signatures are providing great promise for the development of more effective therapeutic strategies in a more personalized and precise manner.To this end,the Cancer Genome Atlas(TCGA) research network conducted a comprehensive molecular evaluation of primary GCs and proposed a new molecular classification dividing GCs into four subtypes:Epstein-Barr virus-associated tumors,microsatellite unstable tumors,genomically stable tumors,and tumors with chromosomal instability.This review primarily focuses on the TCGA molecular classification of GCs and discusses the implications on novel targeted therapy strategies.We believe that these fundamental findings will support the future application of targeted therapies and will guide our efforts to develop more efficacious drugs to treat human GCs.展开更多
The progressive loss of efficacy of standard eradication therapies has made the treatment of Helicobacter pylori (H. pylori) more challenging than ever. Endoscopic-guided antibiotic susceptibility testing had previous...The progressive loss of efficacy of standard eradication therapies has made the treatment of Helicobacter pylori (H. pylori) more challenging than ever. Endoscopic-guided antibiotic susceptibility testing had previously been suggested to guide treatment after failure of second-line therapies. However, its role has expanded over the years, in accordance with the current Maastricht Guidelines. Several authors have dealt with this topic, developing both efficacy trials and cost-effectiveness trials against resistant H. pylori infections as well as infections in naïve patients. However, results are not homogeneous enough to provide definite advice, because antibiotic resistance is not the only reason for treatment failure. Moreover, the culture-guided approach is surrounded by many practical issues, such as the availability of both endoscopy units and microbiology laboratories, and the need for a standard of quality that cannot be satisfied everywhere. Finally, pre-treatment susceptibility testing should be part - and not the only weapon - of a targeted, personalized strategy to overcome H. pylori infection.展开更多
The association between tinnitus and psychological resilience is an underdeveloped area of research.This cross-sectional study investigated such associations and factors potentially affecting resilience in 61 patients...The association between tinnitus and psychological resilience is an underdeveloped area of research.This cross-sectional study investigated such associations and factors potentially affecting resilience in 61 patients.Demographic and psychometric data were collected by questionnaires.The ConnoreDavidson Resilience Scale(CD-RISC),Medical Coping Modes Questionnaire(MCMQ),Satisfaction with Life Scale(SWLS),General Self-Efficacy Scale(GSES),Big Five Inventory(BFI)and Perceived Social Support Scale(PSSS)were completed by participants.Data were analyzed using independent t-test and Pearson's correlation analysis and multiple linear regression modeling.The CD-RISC score was relatively low(66.97±15.71),negatively correlated with tinnitus(r=0.276,p<0.001)and associated with age(r=0.270,P<0.001).As protective factors,SWLS(r=0.486,p<0.001),GSES(r=0.555,p<0.001),PSSS(r=0.538,p<0.001)and extraversion were positively correlated with CD-RISC and BFI scores(r=0.287,p<0.001).We also detected a negative correlation with neuroticism(r=0.395,p<0.001),which is a known risk factor for worse CD-RISC scores.Identifying protective and risk factors for psychological resilience can be used to predict treatment outcomes in tinnitus patients,which will help devise personalized solutions and improve patients'quality of life.展开更多
Healthy homeostasis is a principal driving force of the dynamic equilibrium of living organisms. The dynamical basis of homeostasis is the complex and interconnected feedback mechanisms, which are fundamentally govern...Healthy homeostasis is a principal driving force of the dynamic equilibrium of living organisms. The dynamical basis of homeostasis is the complex and interconnected feedback mechanisms, which are fundamentally governed by the nervous system, mainly the balance of the sympathetic and parasympathetic controlling actions. The balancing regulation is well presented in the heart’s sinus node and can be measured by the time-domain heart-rate variation (HRV) of its frequency domain to analyze the constitutional frequencies of the variation. This last is a fluctuation that shows 1/f time fractal arrangement (f is the composing frequency). The time-fractal arrangement could depend on the structural fractal of the His-Purkinje system of the heart and personally modify the HRV. The cancers gradually destroy the homeostatic harmony, starting locally and finishing systemically. The controlling activity of vagus-nerve changes the HRV or the power density spectrum of the signal fluctuations in malignant development, presenting an appropriate control of the cancerous processes. The modified spectrum by a non-invasive radiofrequency treatment could arrest the tumor growth. An appropriate modulation could support the homeostatic control and force reconstructing of the broken complexity.展开更多
In this editorial we comment on the interesting article by Liu et al.The topic of discussion is the need for a cost-effective and easy-to-use scoring system for predicting the prognosis of colorectal cancer patients.I...In this editorial we comment on the interesting article by Liu et al.The topic of discussion is the need for a cost-effective and easy-to-use scoring system for predicting the prognosis of colorectal cancer patients.In this context,nutritional assessment plays a crucial role in the multimodal evaluation of patients.In particular,the controlling nutritional status score was found to be an effective tool in the clinical decision-making process,in order to customize treatment strategies and to improve patient outcomes.展开更多
Drug-induced pancreatitis is a gastrointestinal adverse effect concerning about 2%of drugs.The majority of cases are mild to moderate but severe episodes can also occur,leading to hospitalization or even death.Unfortu...Drug-induced pancreatitis is a gastrointestinal adverse effect concerning about 2%of drugs.The majority of cases are mild to moderate but severe episodes can also occur,leading to hospitalization or even death.Unfortunately,the mechanisms of this adverse reaction are still not clear,hindering its prevention,and the majority of data available of this potentially life-threatening adverse effect are limited to case reports leading to a probable underestimation of this event.In particular,in this editorial,special attention is given to thiopurine-induced pancreatitis(TIP),an idiosyncratic adverse reaction affecting around 5%of inflammatory bowel disease(IBD)patients taking thiopurines as immunosuppressants,with a higher incidence in the pediatric population.Validated biomarkers are not available to assist clinicians in the prevention of TIP,also because of the inaccessibility of the pancreatic tissue,which limits the possibility to perform dedicated cellular and molecular studies.In this regard,induced pluripotent stem cells(iPSCs)and the exocrine pancreatic differentiated counterpart could be a great tool to investigate the cellular and molecular mechanisms underlying the development of this undesirable event.This particular type of stem cells is obtained by reprogramming adult cells,including fibroblasts and leukocytes,with a set of transcription factors known as the Yamanaka’s factors.Maintaining unaltered the donors’genetic heritage,iPSCs represent an innovative model to study the mechanisms of adverse drug reactions in individual patients’tissues not easily obtainable from human probands.Indeed,iPSCs can differentiate under adequate stimuli into almost any somatic lineage,opening a new world of opportunities for researchers.Several works are already available in the literature studying liver,central nervous system and cardiac cells derived from iPSCs and adverse drug effects.However,to our knowledge no studies have been performed on exocrine pancreas differentiated from iPSCs and drug-induced pancreatitis,so far.Hence,in this editorial we focus specifically on the description of the study of the mechanisms of TIP by using IBD patient-specific iPSCs and exocrine pancreatic differentiated cells as innovative in vitro models.展开更多
Tumor models in vitro are conventional methods for developing anti-cancer drugs,evaluating drug delivery,or calculating drug efficacy.However,traditional cell line-derived tumor models are unable to capture the tumor ...Tumor models in vitro are conventional methods for developing anti-cancer drugs,evaluating drug delivery,or calculating drug efficacy.However,traditional cell line-derived tumor models are unable to capture the tumor heterogeneity in patients or mimic the interaction between tumors and their surroundings.Recently emerging patient-derived preclinical cancer models,including of patient-derived xenograft(PDX)model,circulating tumor cell(CTC)-derived model,and tumor organoids-on-chips,are promising in personalized drug therapy by reca-pitulating the complexities and personalities of tumors and surroundings.These patient-derived models have demonstrated potential advantages in satisfying the rigorous demands of specificity,accuracy,and efficiency necessary for personalized drug therapy.However,the selection of suitable models is depending on the specific therapeutic requirements dictated by cancer types,progressions,or the assay scale.As an example,PDX models show remarkable advantages to reconstruct solid tumors in vitro to understand drug delivery and metabolism.Similarly,CTC-derived models provide a sensitive platform for drug testing in advanced-stage patients,while also facilitating the development of drugs aimed at suppressing tumor metastasis.Meanwhile,the demand for large-scale testing has promoted the development of tumor organoids-on-chips,which serves as an optimal tool for high-throughput drug screening.This review summarizes the establishment and development of PDX,CTC-derived models,and tumor organoids-on-chips and addresses their distinctive advantages in drug discovery,sensitive testing,and screening,which demonstrate the potential to aid in the selection of suitable models for fundamental cancer research and clinical trials,and further developing the personalized drug therapy.展开更多
We start with a description of the statistical inferential framework and the duality between observed data and the true state of nature that underlies it. We demonstrate here that the usual testing of dueling hypothes...We start with a description of the statistical inferential framework and the duality between observed data and the true state of nature that underlies it. We demonstrate here that the usual testing of dueling hypotheses and the acceptance of one and the rejection of the other is a framework which can often be faulty when such inferences are applied to individual subjects. This follows from noting that the statistical inferential framework is predominantly based on conclusions drawn for aggregates and noting that what is true in the aggregate frequently does not hold for individuals, an ecological fallacy. Such a fallacy is usually seen as problematic when each data record represents aggregate statistics for counties or districts and not data for individuals. Here we demonstrate strong ecological fallacies even when using subject data. Inverted simulations, of trials rightly sized to detect meaningful differences, yielding a statistically significant p-value of 0.000001 （1 in a million） and associated with clinically meaningful differences between a hypothetical new therapy and a standard therapy, had a proportion of instances of subjects with standard therapy effect better than new therapy effects close to 30%. A ―winner take all‖ choice between two hypotheses may not be supported by statistically significant differences based on stochastic data. We also argue the incorrectness across many individuals of other summaries such as correlations, density estimates, standard deviations and predictions based on machine learning models. Despite artifacts we support the use of prospective clinical trials and careful unbiased model building as necessary first steps. In health care, high touch personalized care based on patient level data will remain relevant even as we adopt more high tech data-intensive personalized therapeutic strategies based on aggregates.展开更多
Background:Treatment guidelines for a variety of cancers have been increasingly used in clinical practice,and have resulted in major improvement in patient outcomes.However,recommended regimens(even first-line treat-m...Background:Treatment guidelines for a variety of cancers have been increasingly used in clinical practice,and have resulted in major improvement in patient outcomes.However,recommended regimens(even first-line treat-ments)are clearly not ideal for every patients.In the present study,we used mini patient-derived xenograft(mini-PDX)and next-generation sequencing to develop personalized treatment in a patient with metastatic duodenal adenocarcinoma.Methods:Resected metachronous metastatic tumor tissues were implanted into SCID mice to determine the sensitivity to a variety of drug regimens.Mutation profiles were assessed using both DNA whole-exome sequencing(DNA-WES)and RNA sequencing.The results of the analyses were used to select optimal treatment for the patient with metastatic duodenal adenocarcinoma.Results:Assessment with mini-PDX models took only 7 days.The results showed high sensitivity to S-1 plus cis-platin,gemcitabine plus cisplatin and everolimus alone.The patient received gemcitabine plus cisplatin initially,but the treatment was terminated due to toxicity.The patient was then switched to treatment with S-1 alone.The overall disease-free survival was 34 months.DNA-WES and RNA sequencing identified KRAS mutation(A146T),TP53(C229Yfs*10)and RICTOR amplification in the metastatic duodenal adenocarcinoma.These findings provided further support to the results of the mini-PDX,and suggest mTOR inhibitors should be used if and when relapse eventually occurs in this patient.Conclusions:Mini-PDX model combined with WES/RNA sequencing can rapidly assess drug sensitivity in cancer patients and reveal key genetic alterations.Further research on this technology for personalized therapy in patients with refractory malignant tumors is warranted.展开更多
文摘Diabetes mellitus(DM)comprises distinct subtypes-including type 1 DM,type 2 DM,and gestational DM-all characterized by chronic hyperglycemia and sub-stantial morbidity.Conventional diagnostic and therapeutic strategies often fall short in addressing the complex,multifactorial nature of DM.This review ex-plores how multi-omics integration enhances our mechanistic understanding of DM and informs emerging personalized therapeutic approaches.We consolidated genomic,transcriptomic,proteomic,metabolomic,and microbiomic data from major databases and peer-reviewed publications(2015-2025),with an emphasis on clinical relevance.Multi-omics investigations have identified convergent mole-cular networks underlyingβ-cell dysfunction,insulin resistance,and diabetic complications.The combination of metabolomics and microbiomics highlights critical interactions between metabolic intermediates and gut dysbiosis.Novel biomarkers facilitate early detection of DM and its complications,while single-cell multi-omics and machine learning further refine risk stratification.By dissecting DM heterogeneity more precisely,multi-omics integration enables targeted in-terventions and preventive strategies.Future efforts should focus on data har-monization,ethical considerations,and real-world validation to fully leverage multi-omics in addressing the global DM burden.
基金supported by National Natural Science Foundation of China[No.U1608281]National Natural Science Foundation of China[81903658]+2 种基金Liaoning Province Scientific Research Foundation[JC2019032]Liaoning Revitalization Talents Program[No.XLYC1807201]Shenyang S&T Projects[19-109-4-09].
文摘Colorectal cancer(CRC)is one of the most commonly diagnosed cancers worldwide and 30%of patients with CRC experience metastasis.Patients with metastatic colorectal cancer(mCRC)have a 5-year overall survival rate of<10%.V-raf murine sarcoma viral oncogene homolog B1(BRAF)and V-Ki-ras2 Kirsten ratsarcoma viral oncogene homolog(KRAS)mutations are mostly studied in mCRC,as clinical trials found that first-line chemotherapy with anti-epidermal growth factor receptor agent confers limited efficacy for mCRC.Treatment decisions for early-stage mCRC do not consider BRAF or KRAS mutations,given the dramatically poor prognosis conferred by these mutations in clinical trials.Thus,it is necessary to identify patients with mCRC harboring BRAF or KRAS mutations to formulate rational therapeutic strategies to improve prognosis and survival.BRAF and KRAS mutations occur in10%and44%of patients with mCRC,respectively.Although the survival rate of patients with mCRC has improved in recent years,the response and prognosis of patients with the aforementioned mutations are still poor.There is a substantial unmet need for prospective personalized therapies for patients with BRAF-or KRAS-mutant mCRC.In this review,we focus on BRAF and KRAS mutations to understand the mechanisms underlying resistance and improving the response rate,outcomes,and prognosis of patients with mCRC bearing these mutations and to discuss prospective personalized therapies for BRAF-and KRAS-mutant mCRC.
文摘Diabetes mellitus （DM） is one of the most common ＇metabolic disorders in the world~ in which more than90% are grouped to type 2 DM （T2DM）.1 T2DM is characterized by decreased insulin sensitivity and impaired insulin secretion2 leading to hyperglycemia, and the serum glucose has been used as a golden standard for diabetes diagnosis. However, T2DM is a kind of disease involving defects of multiple organs, which cannot be distinguished through the measurement of the serum-glucose level. In addition, T2DM is a multiple-stage disease, which usually covers several decades from impaired plasma glucose to various complications. The serum-glucose level only reflects the consequence of multiole physiological disorders in the Riven stare.
基金the Russian Science Foundation(No.16-15-00010to RRI)the Russian Government Program of Competitive Growth of Kazan Federal University。
文摘We previously demonstrated that gene-modified umbilical cord blood mononuclear cells overexpressing a combination of recombinant neurotrophic factors are a promising therapeutic approach for cell-mediated gene therapy for neurodegenerative diseases,neurotrauma,and stroke.In this study,using a mini pig model of spinal cord injury,we proposed for the first time the use of gene-modified leucoconcentrate prepared from peripheral blood in the plastic blood bag for personalized ex vivo gene therapy.Leucoconcentrate obtained from mini pig peripheral blood was transduced with a chimeric adenoviral vector(Ad5/35 F)that carried an enhanced green fluorescent protein(EGFP)reporter gene in the plastic blood bag.The day after blood donation,the mini pigs were subjected to moderate SCI and four hours post-surgery they were intravenously autoinfused with gene-modified leucoconcentrate.A week after gene-modified leucoconcentrate therapy,fluorescent microscopy revealed EGFP-expressing leucocytes in spinal cord at the site of contusion injury.In the spleen the groups of EGFP-positive cells located in the lymphoid follicles were observed.In vitro flow cytometry and fluorescent microscopy studies of the gene-modified leucoconcentrate samples also confirmed the production of EGFP by leucocytes.Thus,the efficacy of leucocytes transduction in the plastic blood bag and their migratory potential suggest their use for temporary production of recombinant biologically active molecules to correct certain pathological conditions.This paper presents a proof-of-concept of simple,safe and effective approach for personalized ex vivo gene therapy based on gene-modified leucoconcentrate autoinfusion.The animal protocols were approved by the Kazan State Medical University Animal Care and Use Committee(approval No.5)on May 27,2014.
文摘Keloids,which are abnormal manifestations of wound healing,can result in significant functional impairment and aesthetic deformities.The pathogenesis of keloids is multifaceted and complex and influenced by various factors,such as genetics,the environment,and immune responses.The evolution of keloid treatment has progressed from traditional surgical excision to a contemporary combination of therapies including injection and radiation treatments,among others.This article provides a comprehensive review of keloid pathogenesis and treatment,emphasizing the latest advances in the field.Ultimately,this review underscores the necessity for continued research to enhance our understanding of keloid pathogenesis and to devise more effective treatments for this challenging condition.
基金J. Chad Brenner received funding from NIH (Grants No. U01DE025184 and P30: CA046592 S1)Andrew C. Birkeland and Rebecca Hoesli received support from University of Michigan Otolaryngology Resident Research (Grant No. T32DC005356)Megan L. Ludwig was supported by NIH (Grant No. T-32-GM007315)
文摘Laryngeal squamous cell carcinoma(LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for LSCC has stagnated over the past few decades. As the era of next-generation sequencing and personalized treatment for cancer approaches, LSCC may be an ideal disease for consideration of further treatment stratification and personalization. Here, we will discuss the important history of LSCC as a model system for organ preservation, unique and potentially targetable genetic signatures of LSCC, and methods for bringing stratified, personalized treatment strategies to the 21^(st) century.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82103614 and 32171363)Natural Science Foundation of Fujian Province of China(Grant No.2021J05007)+4 种基金funding from the start-up fund for Fujian Key Laboratory of Precision Diagnosis and Treatment in Breast CancerXiamen’s Key Laboratory of Precision Medicine for Endocrine-Related Cancersstart-up and supporting funds from the Third Affiliated Hospital of Kunming Medical University,Yunnan Cancer Hospital for Guo-Jun Zhang and Jing-Wen BaiKey Research and development program for social development of Yunnan Science and Technology Department(Grant No.202403AC100014-2)horizontal project funding from the Third Affiliated Hospital of Kunming Medical University(Grant Nos.20233160A0866 and 20243160A0511)。
文摘The management of breast cancer,one of the most common and heterogeneous malignancies,has transformed with the advent of precision medicine.This review explores current developments in genetic profiling,molecular diagnostics,and targeted therapies that have revolutionized breast cancer treatment.Key innovations,such as cyclin-dependent kinases 4/6(CDK4/6)inhibitors,antibodydrug conjugates(ADCs),and immune checkpoint inhibitors(ICIs),have improved outcomes for hormone receptor-positive(HR+),HER2-positive(HER2+),and triple-negative breast cancer(TNBC)subtypes remarkably.Additionally,emerging treatments,such as PI3K inhibitors,poly(ADP-ribose)polymerase(PARP)inhibitors,and m RNA-based therapies,offer new avenues for targeting specific genetic mutations and improving treatment response,particularly in difficult-to-treat breast cancer subtypes.The integration of liquid biopsy technologies provides a non-invasive approach for real-time monitoring of tumor evolution and treatment response,thus enabling dynamic adjustments to therapy.Molecular imaging and artificial intelligence(AI)are increasingly crucial in enhancing diagnostic precision,personalizing treatment plans,and predicting therapeutic outcomes.As precision medicine continues to evolve,it has the potential to significantly improve survival rates,decrease recurrence,and enhance quality of life for patients with breast cancer.By combining cutting-edge diagnostics,personalized therapies,and emerging treatments,precision medicine can transform breast cancer care by offering more effective,individualized,and less invasive treatment options.
文摘In this editorial we comment on the article published in the recent issue of World Journal of Gastrointestinal Oncology.This study aims to explore the relationship be-tween preoperative inflammation markers and the recurrence of gastrointestinal stromal tumors(GIST)after surgery.It is well known that the best-documented prognostic parameters for GIST are mitotic activity,tumor size and anatomical site.Besides,mutation status represents a prognostic as well as predictive factor.This study provides a new tool for postoperative recurrence risk assessment of GIST patients by establishing a line chart prediction model,which is certificated by previous research that high platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio correlated with increased tumour sizes,more advanced tumour stages and mitotic index.However,as a retrospective study,inevitable bias exists in the results;furthermore,the sample size of this study is relatively small,in-fluencing the universality of the results.Moreover,when assessing risk rating and prognosis of GIST,some novel inflammatory makers could be taken into consi-deration,such as proenkephalin and SLITRK3.Overall,this study can offer an additional model for GIST prognosis and recurrence risk assessment,indepen-dent of the traditional prognostic factors of GIST.
文摘In the unrelenting race to strive to dominate type 2 diabetes mellitus(T2DM)care better,this review paper sets out on a significant discovery trip across recent advancements in treatment and the blooming era of artificial intelligence(AI)utilities.Given the considerable global burden of T2DM,innovative therapeutic approaches to improve patient outcomes remain a public health priority.This review first provides an in-depth analysis of the current state of therapy,from novel pharmacotherapy to lifestyle interventions and new treatment methods.At the same time,the rapidly increasing role of AI in diabetes care is woven into the story,mainly targeting how insulin therapy can be modified and personalized through algorithms and predictive modelling.It leaves a deep review of their pre-existing synergies,which helps understand how collaborative opportunities will unlock the future of T2DM care.This critical role is shown by integrating recent therapeutic advances and AI with overall showcasing better screening,diagnosis,and therapeutics decision-making to outcome prediction in T2DM.The review emphasizes how AI applications in insulin therapy have transformative potential in diabetes care.These person-centred approaches to T2DM management,which are more effective and personalized than some traditional strategies,only work because of the often-hidden synergies between AI algorithms in areas such as diagnostic criteria,predictive methods,and familiar classification tools for subgroups with relevant aspects/predictors on prognosis or treatment responsiveness.
文摘Nocardiosis remains a rare and often underdiagnosed bacterial infection,particularly in immunocompromised individuals.The case report by Zhang et al highlights the diagnostic and therapeutic challenges in managing Nocardia brasiliensis skin infection in a 93-year-old patient with chronic renal insufficiency.This editorial explores the importance of timely diagnosis,microbiological confirmation,and tailored antibiotic therapy.Emphasis is placed on the role of immune status evaluation,drug concentration monitoring,and the necessity of long-term antimicrobial therapy.Improved clinician awareness and adherence to evidencebased management protocols are essential to achieving better outcomes in nocardiosis cases.
基金Supported by Grant from the William E McElroy Foundation,Springfield,IL 62794-9264,United States to Gondi CSthe Carrie M.Craig Medical Student Summer Research Fellowship Program sponsored by the University of Illinois College of Medicine at Peoria,Box 1649,Peoria,IL 61656-1649,United States to Rossi ML
文摘Since its initial characterization, pancreatic ductal adenocarcinoma has remained one of the most devastating and difficult cancers to treat. Pancreatic cancer is the fourth leading cause of death in the United States, resulting in an estimated 38460 deaths annually. With few screening tools available to detect this disease at an early stage, 94% of patients will die within five years of diagnosis. Despite decades of research that have led to a better understanding of the molecular and cellular signaling pathways in pancreatic cancer cells, few effective therapies have been developed to target these pathways. Other treatment options have included more sophisticated pancreatic cancer surgeries and combination therapies. While outcomes have improved modestly for these patients, more effective treatments are desperately needed. One of the greatest challenges in the future of treating this malignancy will be to develop therapies that target the tumor microenvironment and surrounding pancreatic cancer stem cells in addition to pancreatic cancer cells. Recent advances in targeting pancreatic stellate cells and the stroma have encouraged researchers to shift their focus to the role of desmoplasia in pancreatic cancer pathobiology in the hopes of developing newer-generation therapies. By combining novel agents with current cytotoxic chemotherapies and radiation therapy and personalizing them to each patient based on specific biomarkers, the goal of prolonging a patient’s life could be achieved. Here we review the most effective therapies that have been used for the treatment of pancreatic cancer and discuss the future potential of therapeutic options.
基金supported by the National Natural Science Foundation of China(No.81502523)
文摘Gastric cancer(GC) is a highly aggressive and life-threatening malignancy.Even with radical surgical removal and front-line chemotherapy,more than half of GCs locally relapse and metastasize at a distant site.The dismal outcomes reflect the ineffectiveness of a one-size fits-all approach for a highly heterogeneous disease with diverse etiological causes and complex molecular underpinnings.The recent comprehensive genomic and molecular profiling has led to our deepened understanding of GC.The emerging molecular classification schemes based on the genetic,epigenetic,and molecular signatures are providing great promise for the development of more effective therapeutic strategies in a more personalized and precise manner.To this end,the Cancer Genome Atlas(TCGA) research network conducted a comprehensive molecular evaluation of primary GCs and proposed a new molecular classification dividing GCs into four subtypes:Epstein-Barr virus-associated tumors,microsatellite unstable tumors,genomically stable tumors,and tumors with chromosomal instability.This review primarily focuses on the TCGA molecular classification of GCs and discusses the implications on novel targeted therapy strategies.We believe that these fundamental findings will support the future application of targeted therapies and will guide our efforts to develop more efficacious drugs to treat human GCs.
文摘The progressive loss of efficacy of standard eradication therapies has made the treatment of Helicobacter pylori (H. pylori) more challenging than ever. Endoscopic-guided antibiotic susceptibility testing had previously been suggested to guide treatment after failure of second-line therapies. However, its role has expanded over the years, in accordance with the current Maastricht Guidelines. Several authors have dealt with this topic, developing both efficacy trials and cost-effectiveness trials against resistant H. pylori infections as well as infections in naïve patients. However, results are not homogeneous enough to provide definite advice, because antibiotic resistance is not the only reason for treatment failure. Moreover, the culture-guided approach is surrounded by many practical issues, such as the availability of both endoscopy units and microbiology laboratories, and the need for a standard of quality that cannot be satisfied everywhere. Finally, pre-treatment susceptibility testing should be part - and not the only weapon - of a targeted, personalized strategy to overcome H. pylori infection.
基金supported by grants from the Chinese National Nature Science Foundation Research Grant(81670914,81870707)the Postdoctoral Start-Up Fund(zc572016003)Shanxi Key Research and Development Plan(201803D31128).
文摘The association between tinnitus and psychological resilience is an underdeveloped area of research.This cross-sectional study investigated such associations and factors potentially affecting resilience in 61 patients.Demographic and psychometric data were collected by questionnaires.The ConnoreDavidson Resilience Scale(CD-RISC),Medical Coping Modes Questionnaire(MCMQ),Satisfaction with Life Scale(SWLS),General Self-Efficacy Scale(GSES),Big Five Inventory(BFI)and Perceived Social Support Scale(PSSS)were completed by participants.Data were analyzed using independent t-test and Pearson's correlation analysis and multiple linear regression modeling.The CD-RISC score was relatively low(66.97±15.71),negatively correlated with tinnitus(r=0.276,p<0.001)and associated with age(r=0.270,P<0.001).As protective factors,SWLS(r=0.486,p<0.001),GSES(r=0.555,p<0.001),PSSS(r=0.538,p<0.001)and extraversion were positively correlated with CD-RISC and BFI scores(r=0.287,p<0.001).We also detected a negative correlation with neuroticism(r=0.395,p<0.001),which is a known risk factor for worse CD-RISC scores.Identifying protective and risk factors for psychological resilience can be used to predict treatment outcomes in tinnitus patients,which will help devise personalized solutions and improve patients'quality of life.
文摘Healthy homeostasis is a principal driving force of the dynamic equilibrium of living organisms. The dynamical basis of homeostasis is the complex and interconnected feedback mechanisms, which are fundamentally governed by the nervous system, mainly the balance of the sympathetic and parasympathetic controlling actions. The balancing regulation is well presented in the heart’s sinus node and can be measured by the time-domain heart-rate variation (HRV) of its frequency domain to analyze the constitutional frequencies of the variation. This last is a fluctuation that shows 1/f time fractal arrangement (f is the composing frequency). The time-fractal arrangement could depend on the structural fractal of the His-Purkinje system of the heart and personally modify the HRV. The cancers gradually destroy the homeostatic harmony, starting locally and finishing systemically. The controlling activity of vagus-nerve changes the HRV or the power density spectrum of the signal fluctuations in malignant development, presenting an appropriate control of the cancerous processes. The modified spectrum by a non-invasive radiofrequency treatment could arrest the tumor growth. An appropriate modulation could support the homeostatic control and force reconstructing of the broken complexity.
文摘In this editorial we comment on the interesting article by Liu et al.The topic of discussion is the need for a cost-effective and easy-to-use scoring system for predicting the prognosis of colorectal cancer patients.In this context,nutritional assessment plays a crucial role in the multimodal evaluation of patients.In particular,the controlling nutritional status score was found to be an effective tool in the clinical decision-making process,in order to customize treatment strategies and to improve patient outcomes.
基金Supported by Italian Ministry of Health(IRCCS Burlo Garofolo),No.RC 7_2014.
文摘Drug-induced pancreatitis is a gastrointestinal adverse effect concerning about 2%of drugs.The majority of cases are mild to moderate but severe episodes can also occur,leading to hospitalization or even death.Unfortunately,the mechanisms of this adverse reaction are still not clear,hindering its prevention,and the majority of data available of this potentially life-threatening adverse effect are limited to case reports leading to a probable underestimation of this event.In particular,in this editorial,special attention is given to thiopurine-induced pancreatitis(TIP),an idiosyncratic adverse reaction affecting around 5%of inflammatory bowel disease(IBD)patients taking thiopurines as immunosuppressants,with a higher incidence in the pediatric population.Validated biomarkers are not available to assist clinicians in the prevention of TIP,also because of the inaccessibility of the pancreatic tissue,which limits the possibility to perform dedicated cellular and molecular studies.In this regard,induced pluripotent stem cells(iPSCs)and the exocrine pancreatic differentiated counterpart could be a great tool to investigate the cellular and molecular mechanisms underlying the development of this undesirable event.This particular type of stem cells is obtained by reprogramming adult cells,including fibroblasts and leukocytes,with a set of transcription factors known as the Yamanaka’s factors.Maintaining unaltered the donors’genetic heritage,iPSCs represent an innovative model to study the mechanisms of adverse drug reactions in individual patients’tissues not easily obtainable from human probands.Indeed,iPSCs can differentiate under adequate stimuli into almost any somatic lineage,opening a new world of opportunities for researchers.Several works are already available in the literature studying liver,central nervous system and cardiac cells derived from iPSCs and adverse drug effects.However,to our knowledge no studies have been performed on exocrine pancreas differentiated from iPSCs and drug-induced pancreatitis,so far.Hence,in this editorial we focus specifically on the description of the study of the mechanisms of TIP by using IBD patient-specific iPSCs and exocrine pancreatic differentiated cells as innovative in vitro models.
基金supported by the National Natural Science Foundation of China(31971239,11932014)Sichuan Science and Technology Program(2022NSFSC0765,2022ZYD0079).
文摘Tumor models in vitro are conventional methods for developing anti-cancer drugs,evaluating drug delivery,or calculating drug efficacy.However,traditional cell line-derived tumor models are unable to capture the tumor heterogeneity in patients or mimic the interaction between tumors and their surroundings.Recently emerging patient-derived preclinical cancer models,including of patient-derived xenograft(PDX)model,circulating tumor cell(CTC)-derived model,and tumor organoids-on-chips,are promising in personalized drug therapy by reca-pitulating the complexities and personalities of tumors and surroundings.These patient-derived models have demonstrated potential advantages in satisfying the rigorous demands of specificity,accuracy,and efficiency necessary for personalized drug therapy.However,the selection of suitable models is depending on the specific therapeutic requirements dictated by cancer types,progressions,or the assay scale.As an example,PDX models show remarkable advantages to reconstruct solid tumors in vitro to understand drug delivery and metabolism.Similarly,CTC-derived models provide a sensitive platform for drug testing in advanced-stage patients,while also facilitating the development of drugs aimed at suppressing tumor metastasis.Meanwhile,the demand for large-scale testing has promoted the development of tumor organoids-on-chips,which serves as an optimal tool for high-throughput drug screening.This review summarizes the establishment and development of PDX,CTC-derived models,and tumor organoids-on-chips and addresses their distinctive advantages in drug discovery,sensitive testing,and screening,which demonstrate the potential to aid in the selection of suitable models for fundamental cancer research and clinical trials,and further developing the personalized drug therapy.
文摘We start with a description of the statistical inferential framework and the duality between observed data and the true state of nature that underlies it. We demonstrate here that the usual testing of dueling hypotheses and the acceptance of one and the rejection of the other is a framework which can often be faulty when such inferences are applied to individual subjects. This follows from noting that the statistical inferential framework is predominantly based on conclusions drawn for aggregates and noting that what is true in the aggregate frequently does not hold for individuals, an ecological fallacy. Such a fallacy is usually seen as problematic when each data record represents aggregate statistics for counties or districts and not data for individuals. Here we demonstrate strong ecological fallacies even when using subject data. Inverted simulations, of trials rightly sized to detect meaningful differences, yielding a statistically significant p-value of 0.000001 （1 in a million） and associated with clinically meaningful differences between a hypothetical new therapy and a standard therapy, had a proportion of instances of subjects with standard therapy effect better than new therapy effects close to 30%. A ―winner take all‖ choice between two hypotheses may not be supported by statistically significant differences based on stochastic data. We also argue the incorrectness across many individuals of other summaries such as correlations, density estimates, standard deviations and predictions based on machine learning models. Despite artifacts we support the use of prospective clinical trials and careful unbiased model building as necessary first steps. In health care, high touch personalized care based on patient level data will remain relevant even as we adopt more high tech data-intensive personalized therapeutic strategies based on aggregates.
基金the National Natural Science Foundation of China(No.81472346)the National Key Research and Development Program of China(No.2017ZX10203205).
文摘Background:Treatment guidelines for a variety of cancers have been increasingly used in clinical practice,and have resulted in major improvement in patient outcomes.However,recommended regimens(even first-line treat-ments)are clearly not ideal for every patients.In the present study,we used mini patient-derived xenograft(mini-PDX)and next-generation sequencing to develop personalized treatment in a patient with metastatic duodenal adenocarcinoma.Methods:Resected metachronous metastatic tumor tissues were implanted into SCID mice to determine the sensitivity to a variety of drug regimens.Mutation profiles were assessed using both DNA whole-exome sequencing(DNA-WES)and RNA sequencing.The results of the analyses were used to select optimal treatment for the patient with metastatic duodenal adenocarcinoma.Results:Assessment with mini-PDX models took only 7 days.The results showed high sensitivity to S-1 plus cis-platin,gemcitabine plus cisplatin and everolimus alone.The patient received gemcitabine plus cisplatin initially,but the treatment was terminated due to toxicity.The patient was then switched to treatment with S-1 alone.The overall disease-free survival was 34 months.DNA-WES and RNA sequencing identified KRAS mutation(A146T),TP53(C229Yfs*10)and RICTOR amplification in the metastatic duodenal adenocarcinoma.These findings provided further support to the results of the mini-PDX,and suggest mTOR inhibitors should be used if and when relapse eventually occurs in this patient.Conclusions:Mini-PDX model combined with WES/RNA sequencing can rapidly assess drug sensitivity in cancer patients and reveal key genetic alterations.Further research on this technology for personalized therapy in patients with refractory malignant tumors is warranted.
