Efficacy and clinical outcome of chemotherapy and endocrine therapy as first-line treatment in patients with hormone receptor-positive HER2-negative metastatic breast cancer / 中华医学杂志(英文版)

BACKGROUND@#Endocrine therapy (ET) and ET-based regimens are the preferred first-line treatment options for hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (HR+/HER2- MBC), while chemotherapy (CT) is commonly used in clinical practice. The aim of this study was to investigate the efficacy and clinical outcome of ET and CT as first-line treatment in Chinese patients with HR+/HER2- MBC.@*METHODS@#Patients diagnosed with HR+/HER2-MBC between January 1st, 1996 and September 30th, 2018 were screened from the Chinese Society of Clinical Oncology Breast Cancer database. The initial and maintenance first-line treatment, progression-free survival (PFS), and overall survival (OS) were analyzed.@*RESULTS@#Among the 1877 included patients, 1215 (64.7%) received CT and 662 (35.3%) received ET as initial first-line treatment. There were no statistically significant differences in PFS and OS between patients receiving ET and CT as initial first-line treatment in the total population (PFS: 12.0 vs. 11.0 months, P = 0.22; OS: 54.0 vs . 49.0 months, P =0.09) and propensity score matched population. For patients without disease progression after at least 3 months of initial therapy, maintenance ET following initial CT (CT-ET cohort, n = 449) and continuous schedule of ET (ET cohort, n = 527) had longer PFS than continuous schedule of CT (CT cohort, n = 406) in the total population (CT-ET cohort vs. CT cohort: 17.0 vs . 8.5 months; P <0.01; ET cohort vs . CT cohort: 14.0 vs . 8.5 months; P <0.01) and propensity score matched population. OS in the three cohorts yielded the same results as PFS.@*CONCLUSIONS@#ET was associated with similar clinical outcome to CT as initial first-line treatment. For patients without disease progression after initial CT, switching to maintenance ET showed superiority in clinical outcome over continuous schedule of CT.

Metabolic regulation of macrophage function / 白血病·淋巴瘤

Macrophages have plastic and diverse phenotypes and functions, and they play different roles in host defense, tissue homeostasis and repair, development, and various pathologic processes. Although the classically activated macrophage (M1) and alternatively activated macrophage (M2) phenotypes are widely accepted, most macrophages under physiologic and pathologic conditions are polarized to a continuum of states between the M1 and M2 extreme phenotype poles. In recent years, research on the regulatory mechanisms of M1 and M2 macrophages has made great progress, preliminarily elucidating the role of cellular metabolic reprogramming in macrophage polarization and the role of glycolytic enzymes in controlling inflammatory macrophages. The knowledge lays the foundation for elucidating the mechanisms in the regulation of macrophage functional phenotypes. Tumor-associated macrophages play important roles in the development of tumors. The macrophages in the microenvironment of hematologic malignancies have unique features, and a deep study on them will provide new thoughts and clues for clinical diagnosis and therapeutics.

The mechanism of tumors as aging-related diseases / 白血病·淋巴瘤

The tumors originate from transformation cells caused by gene mutations. These cells are frequently kept at dormant state or detected and cleared by the immune surveillance. The research data show that the hallmarks of tumors and aging share many similarities, which is the biological basis for tumors as aging-related diseases. With the increase of tumor initiation cells and the decline of immune function in the elderly, the morbidity and mortality of tumors steadily increase. The core mechanisms are inflammaging and immunosenescence in the elderly. This article reviews recent advances in the field of tumorigenesis, inflammaging and immunosenescence, which elucidates the hypothesis and possible mechanism that tumors are aging-related diseases.

Cellular composition and function of B-cell lymphoma / 白血病·淋巴瘤

B-cell lymphomas are a group of highly heterogeneous malignancies. The phenotypes of different subtypes depend on the differentiation stage and genetic changes of B-cell, which reflects in the immunophenotype, karyotype and tumor microenvironment changes, especially the differences in the cellular composition of microenvironment. This article reviews the characteristics of B-cell lymphoma cells and the cellular composition of microenvironment, discusses the role of tumor microenvironment cells in the occurrence and development of B-cell lymphoma, which provides new ideas for clinical diagnosis and treatment.

Current opinions on the viral etiology of leukemia / 中国肿瘤临床

Half a century ago,it was confirmed that leukemia could be induced by retroviruses in some animals.There are numerous en-dogenous retroviruses in the human genome.However,retrovirus-related human adult T-cell leukemia is only endemic in some local areas. Recently,an extensive study on apolipoprotein B mRNA editing enzyme catalytic polypeptide 3(APOBEC3)family members has revealed the resistance mechanism in human to retrovirus-induced leukemia.The Epstein-Barr virus is widely spread in the human population and exists as a latent infection in the human body for a long time.It is closely associated with the occurrence and development of some lymphomas and solid tumors,indicating its tumorigenicity.The relationship between other viral infections and leukemia/lymphoma remains unclear. The interaction may be mediated by complex,multistep,and indirect networks,which need to be further illuminated.

Mechanism of herpes virus latent infection and its significance / 白血病·淋巴瘤

Human herpes virus (HHV) spreads widely in a latent-infected way. HHV is divided into 3 kinds and 8 types. Herpes simplex caused by HHV-1 and HHV-2, varicella-zoster caused by HHV-3 and Epstein-Barr virus (EBV) known as HHV-4 and recognized firstly as human tumor virus, are well known in the field of virology. With the application of hematopoietic stem cell transplantation , cytomegalovirus (HHV-5) and HHV-6 have gained an increasing attention. The biological characteristic of HHV is latent infection in a long time and HHV can be reactivated in some immunocompromised individuals. Clarification of latent infection mechanism will help provide targets for therapy and lay a foundation for clinical treatment. This paper summarizes the clinical significance of HHV infection. Taking the mechanism of EBV latent infection as an example, the pathway and significance as well as strategy of co-evolution of organism and virus will be discussed in order to provide clues for prevention and therapy.

Reactivation of human herpesvirus 6 and its clinical significance / 白血病·淋巴瘤

Human herpesvirus 6 (HHV-6) is recognized as a ubiquitous dsDNA virus in human with widespread cell tropism in vivo, which could induce lifelong latent infection and be reactivated in some immunocompromised individuals leading to serious diseases. With the increasing application of hematopoietic stem cell transplantation (HSCT), it is obvious that HHV-6 reactivation has a close relationship with several complications including encephalitis after transplantation. On the other hand, among about 1 % infected people, HHV-6 and subtelomeric region of cell chromosomes in the state of endogenous persistent infection play a part in activated virus infection. As the detection methods make a great progress in HHV-6 detection, clinical data reveals the relationship between HHV-6 reactivation and lots of chronic diseases, especially lymphoma, leukemia as well as some chronic hematopoietic and immunological diseases.

Allee effect in leukemia / 白血病·淋巴瘤

Allee effect is a phenomenon in ecology characterized by a correlation between population size or density and the mean individual fitness of population or species.It is consistent with density dependent phenomenon in biomedical field.Recently,Allee effect has been studied by theoretical biologist in detail for oncology biological research.Leukemia cells,which reside in organic microenvironment,show an obvious Allee effect.The authors compared Allee effect with density dependent growth of leukemia cells based on their work experience and literature data.No principle distinction was found between these two terms.In this paper,Allee effect in leukemia cell culture and leukemia,especially in minimal residual disease,will be discussed in the view of ecology.The association between Allee effect and leukemogenesis and relapse dynamics will also be explored in the future research.

Mechanisms and significance of tumor dormancy / 白血病·淋巴瘤

Dormant follicular lymphoma, prostate carcinoma and breast carcinoma are frequently detected by autopsy of non-tumor patients. Dormancy of malignant cells in hematopoietic malignancies is associated with genesis, development and treatment of these diseases. Dormancy is the universally applied strategy by living organism during survival competition. As the in vivo neoplasm, tumor cells keep this property. Recently, much attention has been paid to the mechanisms of tumor dormancy. These studies not only have theoretical significance, provide new ways for the prevention and treatment of tumors, but also help the understanding of over-diagnosis, over-treatment and provide clues for precise medicine. This paper reviewed cellular mechanism of tumor cell dormancy,immunological and vascular regulation of dormant tumors. The clinical significance,application of these mechanisms and direction of further study, which will provide new clues for the treatment of hematopoietic malignancies, were also discussed.

Origin of tumor stem cells / 白血病·淋巴瘤

Cancer stem cells (CSCs) are units in cancer evolution.The elucidation the origin of CSCs has great significance on prevention and treatment of cancers.This paper discusses possible origins,genetic pathways and mechanisms of CSC on the basis of the literature and authors' research.Normal stem cells could be malignantly transformed to CSC through long term accumulation of gene mutations.Induction to pluripotent stem cells by reprogramming is a possible pathway for somatic cells to become CSCs.Dedifferentiation of cancer cells to CSCs is another pathway.Epithelial-mesenchymal transition (EMT),which is an important mechanism for cellular plasticity,plays important roles in cancer metastasis and stemness of cancer cells.Cell-fusion inducing EMT could be a mechanism for the genesis of CSCs.Infection of some virus is also related to the genesis of CSCs.The complexity of cancer biology was also discussed.

Tumor microevolution and its clinical significance / 白血病·淋巴瘤

As novel organisms,tumors undergo microevolution in limited time and space in vivo.Due to genetic mutations and epigenetic mechanisms,tumor cell clones undergo linear or branching evolution.In most clinic patients,tumors develop through branching evolution pathways,causing tumor heterogeneity and affecting tumor progression.Microevolution is the biological basis for the refractoriness and recurrence of tumors and has been paid attention in research and clinic recently.In this paper,acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are used as examples to demonstrate tumor microevolution and the concept of linear and branching evolution.Questions and perspective in the field of tumor microevolution research are also discussed.

Human endogenous retroviruses and tumors / 白血病·淋巴瘤

Viral etiology of tumor has been studied for a century.Seven human tumor viruses were identified over the past half century.The complexity and regularity of the pathogenic mechanisms of human tumor viruses have been elucidated preliminarily.Human genome sequencing indicated that 8 ％ of human genes were composed of human endogenous retroviruses (HERVs).Owing to the findings that adult T-cell leukemia virus (HTLV) can cause human adult T-cell leukemia and animal exogenous and HERVs can induce tumors and malignant diseases,the relationship between HERVs and human tumors has attracted much attention receutly.Here this article discusses the association of the expression of HERVs with leukemia and solid tumors progression,which may be an important aspect of tumor virology.

Circadian rhythms and hematopoietic tumors / 白血病·淋巴瘤

The disturbance of life rhythm exerts negative influence on modem life.The relationship between the disruption of circadian rhythms and tumor growth has attracted much attention.It has been studied in breast cancer and prostate cancer,and chronotherapeutics has been used for treatment of some cancers in clinic.Researchers have begun to investigate the association of circadian rhythms with leukemia/lymphoma outside China.The literatures were reviewed and the launch of research on this field was appealed.

Viral oncogenesis and tumor virotherapy / 白血病·淋巴瘤

After near a century of research,the diverse and complicated relationship between viruses and tumors has been elucidated gradually.Last century it was demonstrated that some retroviruses and some herpes viruses could induce lymphoma and leukemia in some animals.However,it is more complicated in human.During the last two decades it has been confirmed that several types of hepatitis viruses could cause hepatocellular carcinoma and the relationship between human papillomaviruses and cervix carcinoma has been established.These viral vaccines became useful tools to prevent prevalence of these carcinomas.Because of the successful inoculation of live attenuated viral vaccines all around the world in recent 15 years,oncolytic virotherapy is revived,and provides a novel strategy for treatment of refractory tumors.

Clinical study on depression of aged patients with cerebral stroke hemiplegia convalescence / 中国医师进修杂志

Objective To evaluate the effects of Taoist cognitive psychotherapy on depression of aged patients with cerebral stroke hemiplegia convalescence. Methods Seventy-seven hemiplegia convalescence patients with depression were divided into general treatment group (38 patients, received general back-up psychology therapy) and combined treatment group (39 patients, received general back-up psychology therapy and Taoist cognitive psychotherapy) by random digits table. All patients were treated for 8 weeks and followed up for 6 months. Two groups were evaluated with HAMD and SS-QOL before treatment and at the end of the 2 weeks,4 weeks, 8 weeks and 6 months after treatment. The results were analyzed with statistics. Results In general treatment group, the HAMD scores were gradually decreased, and the HAMD scores of patients after 8 weeks' treatment were significantly lower than those before treatment[(22.35 ± 4.69)scores vs. (29.62 ± 5.95 ) scores,t = 6.425 ,P ＜ 0.01]. At the end of 6 months after treatment, the scores increased [(24.48 ± 4.12 ) scores vs. (22.35 ± 4.69 ) scores, t = 2.014, P ＜ 0.05], but they were lower than those before treatment(t = 4.836, P ＜ 0.01 ). At the end of 6 months after treatment, the SS-QOL scores were lower than those after 8 weeks' treatment (t =2.543,P ＜0.05),but they were higher than those before treatment (t = 2.790,P ＜ 0.05 ). In combined treatment group, the HAMD scores decreased continuously,and the scores after 8 weeks' treatment [(20.08 ± 4.60) scores] and 6 months' treatment [( 15.21 ± 3.42)scores] were significantly lower than those before treatment [( 30.14 ± 4.92 ) scores] (t = 8.341,15.443, P ＜0.01). Meanwhile,the HAMD scores after 6 months'treatment were significantly Iower than those after 8 weeks' treatment (t =4.724,P ＜ 0.01 ). The SS-QOL scores after 8 weeks' treatment [( 117.56 ± 26.22)scores] and 6 months' treatment [(126.57 ±21.82) scores] were significantly higher than those before treatment[(86.54 ± 23.90) scores] (t = 6.716,8.916,P ＜ 0.01 ) ,and there was significantly difference(t=2.378,P ＜ 0.05). The HAMD scores of combined treatment group after 8 weeks' and 6 months' treatment were significantly lower than those of general treatment group at the same time(t = 2.118, P ＜ 0.05 ;t = 8.405,P＜ 0.01 ) ,and SS-QOL scores were significantly higher than those of general treatment group at the same time (t = 3.123,P ＜ 0.05 ;t = 6.580,P ＜ 0.01 ). Conclusions General back-up psychology therapy combined with Taoist cognitive psychotherapy can improve depression and life quality of cerebral stroke hemiplegia convalescence in aged patients. The effects of Taoist cognitive psychotherapy is slower, but it is more beneficial in the long time.

Human herpesviruses and tumor / 白血病·淋巴瘤

Human herpesviruses (HHV) are widespread all over the world,and persist in human in latent infection.When reactivated,HHV plays an important role in the pathogenesis and development of tumor and other diseases.Much attention has been paid on EB virus which can cause different tumors and other diseases.Studies within this half century have elucidated the mechanism of oncogenesis of γ-HHV.Recently it was reported that other HHV may have oncomodulation functions.

Effects of mosapride and domperidone on the pulmonary infection of acute stroke patients lying in bed and with nasal feeding / 中国医师进修杂志

Objective To study the effects of mosapride and domperidone on the pulmonary infection of acute stroke patients lying in bed and with nasal feeding. Methods Eighty-nine acute stroke patients lying in bed and with nasal feeding were divided randomly into the treatment group (47 cases) and the control group (42 cases). The control group was treated routinely,and the treatment group was treated with mosapride 5 mg and domporidone 20 mg thrice a day for 4 weeks, besides routine therapy. The incidence rate of pulmonary infection, gastric residual volume (GRV) and the number of cases with gastric contents remaining after 3 hours of nasal feeding were studied. All data were analyzed statistically. Results In the treatment group, 13 cases had pulmonary infection,and the incidence rate was 27.66%(13/47). In the control group,25 cases had pulmonary infection,and the incidence rate was 59.52% (25/42). There was significant difference between the two groups (P < 0.01 ). Three hours after nasal feeding,24 cases with gastric contents remaining were discovered in the treatment group,and GRV was (50.80±15.38) ml. Two hundred and thirty-seven cases with gastric contents remaining were discovered in the control group, and GRV was (112.17±32.54) ml. Significance differences were also detected between the two groups (P<0.01). Conclusion As for the acute stroke patients lying in bed and with nasal feeding,mosapride and domperidone can remarkably cut down the pulmonary infection upon common treatment.

Classification of cell death and its significance / 白血病·淋巴瘤

Cell death as the partner of cell proliferation is one of the basic mechanism in cell biology. Recently, it became obscure since more and more patterns of cell death were reported. However, the classification of cell death, which was recommended by the Nomenclature Committee on Cell Death (NCCD) in 2009, clarified the criteria. The theme of the recommendation and recent data from the literature were discussed in this review. The significance of studies on cell death was discussed.

Cellular tunneling nanotubes and its significance / 白血病·淋巴瘤

Tunneling nanotubes(TNT) are cellular communication and transport mechanism discovered recently. TNTs play important role in immunological response and viral spread, also may involve embryonic development, regulation of gene expression and carcinogenesis. However, it was not easy to study TNT for clinical samples since intricate assay method for TNT. We suggested using histochemical assay PAS staining in cell drip to show TNT in leukemia and lymphoma samples.