Research progress in tumor angiogenesis and drug resistance in breast cancer

Angiogenesis is considered a hallmark pathophysiological process in tumor development. Aberrant vasculature resulting from tumor angiogenesis plays a critical role in the development of resistance to breast cancer treatments, via exacerbation of tumor hypoxia, decreased effective drug concentrations within tumors, and immune-related mechanisms. Antiangiogenic therapy can counteract these breast cancer resistance factors by promoting tumor vascular normalization. The combination of antiangiogenic therapy with chemotherapy, targeted therapy, or immunotherapy has emerged as a promising approach for overcoming drug resistance in breast cancer. This review examines the mechanisms associated with angiogenesis and the interactions among tumor angiogenesis, the hypoxic tumor microenvironment, drug distribution, and immune mechanisms in breast cancer. Furthermore, this review provides a comprehensive summary of specific antiangiogenic drugs, and relevant studies assessing the reversal of drug resistance in breast cancer. The potential mechanisms underlying these interventions are discussed, and prospects for the clinical application of antiangiogenic therapy to overcome breast cancer treatment resistance are highlighted.

Experimental study on effect of recombinant human growth hormone combined with chemotherapy on stomach neoplasms implanted in nude mice

Objective: To investigate the effect of different doses of recombined growth hormone (rhGH) on stomach neo- plasms implanted in nude mice, and its efficacy in combining with chemotherapy (flurouracil, 5-FU). Methods: Human stom- ach neoplasms model was established in nude mice. The nude mice were divided into control group, moderate-dose of rhGH group, low-dose rhGH group, 5-FU group, moderate-dose rhGH/5-FU group, and low-dose rhGH/5-FU group. The results of each group were observed after ten days. Results: After therapy, the body mass of rhGH groups was significantly increased compared with control group (P<0.05), the body mass of rhGH/5-FU groups was significantly increased compared with 5-FU group (P<0.05), but it was no significant difference between rhGH/5-FU groups and control group (P>0.05). The average tumor mass and volume of rhGH groups were not significantly increased compared with control group (P>0.05), but they were significantly reduced in 5-FU group and rhGH/5-FU groups (P<0.05). They were no significant difference between rhGH/5- FU groups and 5-FU group (P>0.05). After treatment, the percentages of S, G0/G1 and G2/M phases and proliferation index (PI) were not significantly changed in rhGH groups compared with control group (P>0.05), and the same with rhGH/5-FU groups compared with 5-FU group (P>0.05). The difference caused by dose of rhGH was not significant. Conclusion: rhGH enhances body mass, does not stimulate tumor growth, and has no adverse effects on tumor bearing nude mice. Combined with flurouracil, rhGH does not influence the efficacy of chemotherapy, and has no effect on tumor cell cycle kinetics.

Early prediction of pathological outcomes to neoadjuvant chemotherapy in breast cancer patients using automated breast ultrasound

Objective： Early assessment of response to neoadjuvant chemotherapy （NAC） for breast cancer allows therapy to be individualized. The optimal assessment method has not been established. We investigated the accuracy of automated breast ultrasound （ABUS） to predict pathological outcomes after NAC. Methods： A total of 290 breast cancer patients were eligible for this study. Tumor response after 2 cycles of chemotherapy was assessed using the product change of two largest perpendicular diameters （PC） or the longest diameter change （LDC）. PC and LDC were analyzed on the axial and the coronal planes respectively. Receiver operating characteristic （ROC） curves were used to evaluate overall performance of the prediction methods. Youden＇s indexes were calculated to select the optimal cut-off value for each method. Sensitivity, specificity, positive and negative predictive values （PPV and NPV） and the area under the ROC curve （AUC） were calculated accordingly.Results： ypT0/is was achieved in 42 patients （14.5%） while ypT0 was achieved in 30 patients （10.3%） after NAC. All four prediction methods （PC on axial planes, LDC on axial planes, PC on coronal planes and LDC on coronal planes） displayed high AUCs （all〉0.82）, with the highest of 0.89 [95% confidence interval （95% CI）, 0.83-0.95] when mid-treatment ＆BUS was used to predict final pathological complete remission （pCR）. High sensitivities （85.7%-88.1%） were observed across all four prediction methods while high specificities （81.5%-85.1%） were observed in two methods used PC. The optimal cut-off values defined by our data replicate the WHO and the RECIST criteria. Lower AUCs were observed when mid-treatment ABUS was used to predict poor pathological outcomes. Conclusions：ABUS is a useful tool in early evaluation of pCR after NAC while less reliable when predicting poor pathological outcomes.

Evaluation of menopausal status among breast cancer patients with chemotherapy-induced amenorrhea

Objective： In patients with chemotherapy-induced amenorrhea （CIA）, the menopausal status is ambiguous anddifficult to evaluate. This study aimed to establish a discriminative model to predict and classify the menopausalstatus of breast cancer patients with CIA.Methods： This is a single center hospital-based study from 2013 to 2016. The menopausal age distribution andaccumulated incidence rate of CIA are described. Multivariate models were adjusted for established and potentialconfounding factors including age, serum concentration of estradiol （E2） and follicle-stimulating hormone （FSH）,feeding, pregnancy, parity, abortions, and body mass index （BMI）. The odds ratio （OR） and 95% confidenceinterval （95% CI） of different risk factors were estimated.Results： A total of 1,796 breast cancer patients were included in this study, among whom, 1,175 （65.42%） werepremenopausal patients and 621 （34.58%） were post-menopause patients. Five hundred and fifty patients wereincluded in CIA analysis, and a cumulative CIA rate of 81.64% was found in them. Age （OR： 1.856, 95% CI：1.732-1.990）, serum concentration of E2 （OR： 0.976, 95% CI： 0.972-0.980） and FSH （OR： 1.060, 95% CI：1.053-i.066）, and menarche age （OR： 1.074, 95% CI： 1.009-1.144） were found to be associated with the patients＇menopausal status. According to multivariate analysis, the discriminative model to predict the menopausal status isLogit （P）=-28.396＋0.536Age-0.014E2＋0.031FSH. The sensitivities for this model were higher than 85%, and itsspecificities were higher than 89%.Conclusions： The discriminative model obtained from this study for predicting menstrual state is important forpremenopausal patients with CIA. This model has high specificity and sensitivity and should be prudently used.

Identification of the Interaction between P-Glycoprotein and Anxa2 in Multidrug-resistant Human Breast Cancer Cells

Objective To explore the interaction of Anxa2 with P-Glycoprotein （P-gp） in the migration and invasion of the multidrug-resistant （MDR） human breast cancer cell line MCF-7/ADR. Methods A pair of short hairpin RNA （shRNA） targeting P-gp was transfected into MCF-7/ADR cells, and monoclonal cell strains were screened. The expression of P-gp was detected by Western blot. Transwell chambers were used to observe the cell migration capacity and invasion ability. The interaction between P-gp and Anxa2 was examined by immunoprecipitation and immunofluorescence confocal microscopy analyses. Results P-gp expression was significantly knocked down, and there were notable decreasing trends in the migration and invasion capability of MDR breast cancer cells （P〈0.05）. There was a close interaction between Anxa2 and P-gp. Conclusions MCF-7/ADR is an MDR human breast cancer cell line with high migration and invasion abilities. The knockdown of P-gp notably impaired the migration and invasion abilities of the tumor cells. The interaction of Anxa2 with P-pg may play an important role in time enhanced invasiveness of MDR human breast cancer cells.

Photodynamic Therapy for Gynecological Diseases and Breast Cancer

Photodynamic therapy （PDT） is a minimally invasive and promising new method in cancer treatment. Cytotoxic reactive oxygen species （ROS） are generated by the tissueqocalized non-toxic sensitizer upon illumination and in the presence of oxygen. Thus, selective destruction of a targeted tumor may be achieved. Compared with traditional cancer treatment, PDI has advantages including higher selectivity and lower rate of toxicity. The high degree of selectivity of the proposed method was applied to cancer diagnosis using fluorescence. This article reviews previous studies done on PDT treatment and photodetection of cervical intraepithelial neoplasia, vulvar intraepithelial neoplasia, ovarian and breast cancer, and PDT application in treating non-cancer lesions. The article also highlights the clinical responses to PDT, and discusses the possibility of enhancing treatment efficacy by combination with immunotherapy and targeted therapy.

Paclitaxel-induced stress granules increase LINE-1 mRNA stability to promote drug resistance in breast cancer cells

Abnormal expression of long interspersed element-1(LINE-1)has been implicated in drug resistance,while our previous study showed that chemotherapy drug paclitaxel(PTX)increased LINE-1 level with unknown mechanism.Bioinformatics analysis suggested the regulation of LINE-1 mRNA by drug-induced stress granules(SGs).This study aimed to explore whether and how SGs are involved in drug-induced LINE-1 increase and thereby promotes drug resistance of triple negative breast cancer(TNBC)cells.We demonstrated that SGs increased LINE-1 expression by recruiting and stabilizing LINE-1 mRNA under drug stress,thereby adapting TNBC cells to chemotherapy drugs.Moreover,LINE-1 inhibitor efavirenz(EFV)could inhibit drug-induced SG to destabilize LINE-1.Our study provides the first evidence of the regulation of LINE-1 by SGs that could be an important survival mechanism for cancer cells exposed to chemotherapy drugs.The findings provide a useful clue for developing new chemotherapeutic strategies against TNBCs.

Excellent effects and possible mechanisms of action of a new antibody–drug conjugate against EGFR-positive triple-negative breast cancer

Background:Triple-negative breast cancer(TNBC)is the most aggressive subtype and occurs in approximately 15%–20%of diagnosed breast cancers.TNBC is characterized by its highly metastatic and recurrent features,as well as a lack of specific targets and targeted therapeutics.Epidermal growth factor receptor(EGFR)is highly expressed in a variety of tumors,especially in TNBC.LR004-VC-MMAE is a new EGFR-targeting antibody–drug conjugate produced by our laboratory.This study aimed to evaluate its antitumor activities against EGFR-positive TNBC and further studied its possible mechanism of antitumor action.Methods:LR004-VC-MMAE was prepared by coupling a cytotoxic payload(MMAE)to an anti-EGFR antibody(LR004)via a linker,and the drug-to-antibody ratio(DAR)was analyzed by HIC-HPLC.The gene expression of EGFR in a series of breast cancer cell lines was assessed using a publicly available microarray dataset(GSE41313)and Western blotting.MDA-MB-468 and MDA-MB-231 cells were treated with LR004-VC-MMAE(0,0.0066,0.066,0.66,6.6 nmol/L),and the inhibitory effects of LR004-VC-MMAE on cell proliferation were examined by CCK-8 and colony formation.The migration and invasion capacity of MDA-MB-468 and MDA-MB-231 cells were tested at different LR004-VCMMAE concentrations(2.5 and 5 nmol/L)with wound healing and Transwell invasion assays.Flow cytometric analysis and tumorsphere-forming assays were used to detect the killing effects of LR004-VC-MMAE on cancer stem cells(MDA-MB-468 and MDA-MB-231 cells).The mouse xenograft models were also used to evaluate the antitumor efficacy of LR004-VC-MMAE in vivo.Briefly,BALB/c nude mice were subcutaneously inoculated with MDA-MB-468 or MDAMB-231 cells.Then they were randomly divided into 4 groups(n=6 per group)and treated with PBS,naked LR004(10 mg/kg),LR004-VC-MMAE(10 mg/kg),or doxorubicin,respectively.Tumor sizes and the body weights of mice were measured every 4 d.The effects of LR004-VC-MMAE on apoptosis and cell cycle distribution were analyzed by flow cytometry.Western blotting was used to detect the effects of LR004-VC-MMAE on EGFR,ERK,MEK phosphorylation and tumor stemness marker gene expression.Results:LR004-VC-MMAE with a DAR of 4.02 were obtained.The expression of EGFR was found to be significantly higher in TNBC cells compared with non-TNBC cells(P<0.01).LR004-VC-MMAE inhibited the proliferation of EGFRpositive TNBC cells,and the ICvalues of MDA-MB-468 and MDA-MB-231 cells treated with LR004-VC-MMAE for 72 h were(0.13±0.02)nmol/L and(0.66±0.06)nmol/L,respectively,which were significantly lower than that of cells treated with MMAE[(3.20±0.60)nmol/L,P<0.01,and(6.60±0.50)nmol/L,P<0.001].LR004-VC-MMAE effectively inhibited migration and invasion of MDA-MB-468 and MDA-MB-231 cells.Moreover,LR004-VC-MMAE also killed tumor stem cells in EGFR-positive TNBC cells and impaired their tumorsphere-forming ability.In TNBC xenograft models,LR004-VC-MMAE at 10 mg/kg significantly suppressed tumor growth and achieved complete tumor regression on day 36.Surprisingly,tumor recurrence was not observed until the end of the experiment on day 52.In a mechanistic study,we found that LR004-VC-MMAE significantly induced cell apoptosis and cell cycle arrest at G/M phase in MDAMB-468[(34±5)%vs.(12±2)%,P<0.001]and MDA-MB-231[(27±4)%vs.(18±3)%,P<0.01]cells.LR004-VC-MMAE also inhibited the activation of EGFR signaling and the expression of cancer stemness marker genes such as Oct4,Sox2,KLF4 and EpCAM.Conclusions:LR004-VC-MMAE showed effective antitumor activity by inhibiting the activation of EGFR signaling and the expression of cancer stemness marker genes.It might be a promising therapeutic candidate and provides a potential therapeutic avenue for the treatment of EGFR-positive TNBC.

Evolution of breast cancer therapeutics: Breast tumour kinase's role in breast cancer and hope for breast tumour kinase targeted therapy

There have been significant improvements in the detection and treatment of breast cancer in recent decades. However, there is still a need to develop more effective therapeutic techniques that are patient specific with reduced toxicity leading to further increases in patients' overall survival; the ongoing progress in understanding recurrence, resistant and spread also needs to be maintained. Better understanding of breast cancer pathology, molecular biology and progression as well as identification of some of the underlying factors involved in breast cancer tumourgenesis and metastasis has led to the identification of novel therapeutic targets. Over a number of years interest has risen in breast tumour kinase(Brk) also known as protein tyrosine kinase 6; the research field has grown and Brk has been described as a desirable therapeutic target in relation to tyrosine kinase inhibition as well as disruption of its kinase independent activity. This review will outline the current "state of play" with respect to targeted therapy for breast cancer, as well as discussing Brk's role in the processes underlying tumour development and metas-tasis and its potential as a therapeutic target in breast cancer.

Clinical observation of capecitabine monotherapy in elderly patients with advanced breast cancer

Objective The aim of the study was to evaluate the safety and efficacy of capecitabine mono-chemotherapy in elderly patients with advanced breast cancer. Methods The data from 36 cases of capecitabine monotherapy in elderly patients with advanced breast cancer were retrospectively analyzed. Oral administration of capecitabine 2000 mg/m^2 twice daily （D1-14） for 21 days constituted a cycle. The effect of the disease and main adverse reactions were evaluated every 2 cycles. Results The data from 36 elderly patients were studied. The median number of chemotherapy cycles was 4. The total effective rate was 30.6% （11/36） and the disease control rate was 72.2% （26/36）. The number of patients with clinical comptete remission was 2, clinical partial response was 9, stable disease was 15, and progressive disease was 10. Where treatment was effective, the median time to progression was 6 months and the median overall survival was 9.5 months. The main adverse events were gastrointestinal reactions, bone marrow suppression, and oral mucositis; most of the reactions were grade 1 to 2. Grade 3 to 4 adverse reactions included granulocytopenia in 2 patients （12.5%） and hand-foot syndrome in 1 patient （6.7%）. Conclusion Capecitabine monotherapy was effective in controlling disease progression, and adverse reactions were tolerated by elderly patients with advanced breast cancer.

Immunotherapy for recurrent hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is presented frequently in late stages that are not amenable for curative treatment.Even for patients who can undergo resection for curative treatment of HCC,up to 50%recur.For patients who were not exposed to systemic therapy prior to recurrence,recurrence frequently cannot be subjected to curative therapy or local treatments.Such patients have several options of immunotherapy(IO).This includes programmed cell death protein 1(PD-1)and cytotoxic T-lymphocyte associated protein 4 treatment,combination of PD-1 and vascular endothelial growth factor inhibitor or single agent PD-1 therapy when all other options are deemed inappropriate.There are also investigational therapies in this area that explore either PD-1 and tyrosine kinase inhibitors or a novel agent in addition to PD-1 with vascular endothelial growth factor inhibitors.This minireview explored IO options for patients with recurrent HCC who were not exposed to systemic therapy at the initial diagnosis.We also discussed potential IO options for patients with recurrent HCC who were exposed to first-line therapy with curative intent at diagnosis.

Fatigue and Quality of Life of Women Undergoing Chemotherapy or Radiotherapy for Breast Cancer

OBJECTIVE To examine fatigue and quality of life (QOL) inbreast cancer patients undergoing chemotherapy or radiotherapy.METHODS A self-report survey derived from the Chineseversion of Brief Fatigue Inventory, the Functional Assessmentof Chronic Illness Therapy for Breast Cancer, and the MedicalOutcomes Study Social Support Survey. Descriptive statisticswas used to examine the intensity of fatigue and the prevalenceof severe fatigue. Multivariate analysis of variance was used todetermine factors that affect the five domains of QOL among theparticipants.RESULTS The majority of the participants (n = 261) perceiveda mild level of fatigue, but 35.6% of them suffered severe fatigue.Fatigue had a significantly negative association with all domainsof QOL except social/family wellbeing. The participants whowere receiving chemotherapy, undergoing curative treatment andhaving inadequate social support were more likely to have poorerQOL in all five domains (after adjustment for age).CONCLUSION Although the majority of the participantsexperienced a mild level of fatigue, there was a substantial groupof breast cancer patients who perceived their fatigue as severe. Thefindings of this study showed that fatigue had a detrimental effecton the various aspects of the participants' QOL. Demographic andclinical characteristics of breast cancer patients who were at riskof getting poorer QOL were identified. The results of the studydemonstrate that we should enhance healthcare professionals'awareness of the importance of symptom assessment, andprovide them with information for planning effective symptom-management strategies among this study population.

Breast cancer:Muscarinic receptors as new targets for tumor therapy

The development of breast cancer is a complex process that involves the participation of different factors.Several authors have demonstrated the overexpression of muscarinic acetylcholine receptors(mAChRs)in different tumor tissues and their role in the modulation of tumor biology,positioning them as therapeutic targets in cancer.The conventional treatment for breast cancer involves surgery,radiotherapy,and/or chemotherapy.The latter presents disadvantages such as limited specificity,the appearance of resistance to treatment and other side effects.To prevent these side effects,several schedules of drug administration,like metronomic therapy,have been developed.Metronomic therapy is a type of chemotherapy in which one or more drugs are administered at low concentrations repetitively.Recently,two chemotherapeutic agents usually used to treat breast cancer have been considered able to activate mAChRs.The combination of low concentrations of these chemotherapeutic agents with muscarinic agonists could be a useful option to be applied in breast cancer treatment,since this combination not only reduces tumor cell survival without affecting normal cells,but also decreases pathological neo-angiogenesis,the expression of drug extrusion proteins and the cancer stem cell fraction.In this review,we focus on the previous evidences that have positioned mAChRs as relevant therapeutic targets in breast cancer and analyze the effects of administering muscarinic agonists in combination with conventional chemotherapeutic agents in a metronomic schedule.

Neoadjuvant targeted therapy for apocrine carcinoma of the breast:A case report

BACKGROUND Apocrine carcinoma of the breast is a special type of invasive ductal carcinoma of the breast that is rare in clinical practice.Neoadjuvant therapy,especially neoadjuvant targeted therapy,has rarely been reported for apocrine carcinoma of the breast.CASE SUMMARY A 63-year-old woman presented with apocrine carcinoma of the left breast underwent core needle biopsy.The patient was diagnosed with apocrine carcinoma by immunohistochemical staining and negative hormone status(estrogen receptor and progesterone receptor)but showed overexpression of human epidermal factor receptor 2(HER-2).Moreover,positive expression of androgen receptor(approximately 60%)and gross cystic disease fluid protein 15 was observed.The patient was treated with neoadjuvant targeted therapy consisting of the TCH regimen(docetaxel,carboplatin area under curve 6 and trastuzumab)every 21 d.The mass in the left breast was significantly reduced,and pain in the breast and left upper arm also improved.CONCLUSION HER-2 positive apocrine carcinoma of the breast can be improved by neoadjuvant chemotherapy combined with targeted therapy.

Nicotinic receptors modulate antitumor therapy response in triple negative breast cancer cells

BACKGROUND Triple negative breast cancer is more aggressive than other breast cancer subtypes and constitutes a public health problem worldwide since it has high morbidity and mortality due to the lack of defined therapeutic targets.Resistance to chemotherapy complicates the course of patients’treatment.Several authors have highlighted the participation of nicotinic acetylcholine receptors(nAChR)in the modulation of conventional chemotherapy treatment in cancers of the airways.However,in breast cancer,less is known about the effect of nAChR activation by nicotine on chemotherapy treatment in smoking patients.AIM To investigate the effect of nicotine on paclitaxel treatment and the signaling pathways involved in human breast MDA-MB-231 tumor cells.METHODS Cells were treated with paclitaxel alone or in combination with nicotine,administered for one or three 48-h cycles.The effect of the addition of nicotine(at a concentration similar to that found in passive smokers’blood)on the treatment with paclitaxel(at a therapeutic concentration)was determined using the 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.The signaling mediators involved in this effect were determined using selective inhibitors.We also investigated nAChR expression,and ATP“binding cassette”G2 drug transporter(ABCG2)expression and its modulation by the different treatments with Western blot.The effect of the treatments on apoptosis induction was determined by flow cytometry using annexin-V and 7AAD markers.RESULTS Our results confirmed that treatment with paclitaxel reduced MDA-MB-231 cell viability in a concentration-dependent manner and that the presence of nicotine reversed the cytotoxic effect induced by paclitaxel by involving the expression of functionalα7 andα9 nAChRs in these cells.The action of nicotine on paclitaxel treatment was linked to modulation of the protein kinase C,mitogen-activated protein kinase,extracellular signal-regulated kinase,and NF-κB signaling pathways,and to an up-regulation of ABCG2 protein expression.We also detected that nicotine significantly reduced the increase in cell apoptosis induced by paclitaxel treatment.Moreover,the presence of nicotine reduced the efficacy of paclitaxel treatment administered in three cycles to MDA-MB-231 tumor cells.CONCLUSION Our findings point to nAChRs as responsible for the decrease in the chemotherapeutic effect of paclitaxel in triple negative tumors.Thus,nAChRs should be considered as targets in smoking patients.

Application of phage display technology in targeted therapy of breast cancer

Phage display is a technology of gene expression and screening, it is widely used in the fields of defining antigen epitopes, signal transduction, genetic treatment, parasites research and tumor targeted therapy. Breast cancer is the most common cancer in women, we can obtain peptides specially associated with breast cancer by using phage display technology, and this method has great potential in early diagnosis of breast cancer and development new targeted drugs.

A Predictive Model for Pathologic Complete Response in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy Using Machine Learning

Background: In patients with breast cancer after Neoadjuvant Chemotherapy (NAC), pathological Complete Response (pCR) was associated with better long-term outcomes. We here attempted to predict pCR using machine learning. Patients and Methods: From 2008 to 2017, 1308 breast cancer patients underwent NAC before surgery, of whom 377 patients underwent Cancer SCANTM for gene data. Of 377, 238 were analyzed here, with 139 excluded due to incomplete medical data. Results: The pCR (-) vs. (+) group had 200 vs. 38 patients. In our predictive model with gene data, the Area Under the Curve (AUC) of the Receiver Operating Characteristic (ROC) curve was 0.909 and accuracy was 0.875. In another model without gene data, the AUC of ROC curve was 0.743 and accuracy was 0.800. We also conducted internal validation with 72 patients undergoing NAC and Cancer SCANTM during July 2017 and April 2018. When we applied a 0.4 threshold value, accuracy was 0.806 and 0.778 in the predictive model with vs. without gene profiles, respectively. Conclusion: The present predictive model may be a useful and easy-to-access tool for pCR-prediction in breast cancer patients treated with NAC.

肝癌靶向联合免疫治疗耐药后的二线治疗方案研究进展

近年来,靶向和免疫单药及联合治疗晚期肝癌的临床研究为一线用药方案选择提供了丰富的疗效与安全性证据。然而,对于肝癌二线治疗方案的选择,目前各项临床指南尚无统一意见,原因在于现有循证医学证据局限于索拉非尼失败后的选择,而对于新的一线方案,如靶向免疫联合治疗肝癌耐药后的二线治疗方案,依然缺乏高证据等级的临床试验结论。本文回顾了目前临床试验研究结果,根据药物作用的不同机制,对靶向免疫一线治疗耐药后肝癌二线治疗方案的研究进行了归纳,并系统总结近年研究进展。对于一线靶免联合治疗耐药的肝癌患者,靶向联合治疗、免疫双抗治疗均有望提高疗效、改善生存,未来还需更多前瞻性临床研究数据,为靶免联合治疗耐药的肝癌患者提供有效、安全的治疗方案。

垂体催乳素瘤的临床特点及诊治要点更新--基于《2022版ICCE/AME垂体催乳素瘤临床实践共识》解读

垂体催乳素瘤是一种由垂体催乳素细胞瘤过量合成和分泌催乳素引起的神经内分泌疾病,垂体催乳素瘤的规范化诊疗对于恢复并维持患者的正常垂体功能并提高其生活质量具有重要意义。2022年1月,《欧洲内分泌杂志》发布了国际临床内分泌学分会(ICCE)与意大利临床内分泌学家协会(AME)关于垂体催乳素瘤的临床实践最新共识申明——《2022版ICCE/AME垂体催乳素瘤临床实践共识》(简称2022版ICCE/AME新共识)。2022版ICCE/AME新共识立足最新循证医学证据,对于垂体催乳素瘤的临床诊治问题进行系统性阐述、分析和建议。本文围绕2022版ICCE/AME新共识关于垂体催乳素瘤的诊断、治疗、特殊人群、多巴胺激动剂抵抗及侵袭性疾病等诊治要点更新进行解读,希望有助于全科医生及内分泌专科医生对于垂体催乳素瘤的认识,为其临床实践的规范化诊疗提供参考。

免疫细胞及炎症因子对晚期肺癌一线化疗效果的预测价值

【目的】探讨T淋巴细胞亚群、肿瘤浸润T淋巴细胞(Tils)及炎症因子对晚期肺癌一线化疗效果的预测价值。【方法】检测98例首诊TNM分期为Ⅲ/Ⅳ期的非小细胞肺腺癌患者的血清白细胞介素1α(IL-1α)、IL-6、IL-17、γ-干扰素(INF-γ)水平及T淋巴细胞亚群CD4^(+)T、CD8^(+)T、调节性T细胞、CD57^(+)细胞、Granzyme B^(+)细胞、CD45RO^(+)细胞比例;所有患者均接受紫杉醇注射液+顺铂化疗,治疗4个周期后评定疗效,并据此分为有效组和无效组,分析化疗无效的影响因素及预测疗效的有效标志物。【结果】化疗后,98例患者中69例化疗有效,29例无效。无效组患者淋巴结转移占比及调节性T细胞、IL-1α表达水平均高于有效组(P<0.05),CD57^(+)细胞、CD45RO^(+)细胞比例均低于有效组(P<0.05)。多因素逐步Logistic回归分析结果显示,调节性T细胞、IL-1α水平高是肺癌患者化疗无效的危险因素(P<0.05),CD57^(+)细胞、CD45RO^(+)细胞比例高是保护因素(P<0.05)。受试者工作特征(ROC)曲线分析显示,调节性T细胞、CD57^(+)细胞、CD45RO^(+)细胞、IL-1α水平预测化疗效果的灵敏度分别为82.76%、86.21%、89.66%、93.10%,四者联合的灵敏度、特异度和曲线下面积(AUC)分别为82.76%、97.10%、0.957。【结论】T淋巴细胞亚群、Tils及炎症因子水平与晚期肺癌治疗效果密切相关,其可作为预测疗效的敏感指标。