Serum HER2 Level Predicts Therapeutic Efficacy and Prognosis in Advanced Breast Cancer Patients.

Background: The purpose of this study was to investigate the therapeutic efficacy and prognosis of serum HER2 (sHER2) in patients with advanced breast cancer. Methods: We analyzed the sHER2 levels of 200 patients with advanced breast cancer receiving first or second line treatment, the tissue HER2 (tHER2) level was also analyzed. Indicators of therapeutic efficacy and prognosis were objective response rate (ORR), disease control rate (DCR), and time to progression (TTP). Results: The baseline sHER2 level was high in 132 patients and low in 68 patients. The high level of sHER2 is correlated with molecular subtype (p=0.016), visceral metastasis (p<0.001), liver metastasis (p<0.001), tissue HER-2 (tHER2) (p=0.001), and, among tHER2-low tumors (59 patients), the baseline sHER2 high level was associated with a higher proportion of brain metastasis. The ORR of patients with baseline sHER2 high level is higher than those with baseline sHER2 low level (p=0.026). The TTP of patients with baseline sHER2 low level is longer than the patients with baseline sHER2 high level (p=0.024). For patients with baseline sHER2 high level, a significant decrease in sHER2 after two cycles of treatment indicates higher ORR, DCR, and an extension of TTP. After multiple cycles of treatment, for patients with tHER-2 positive and baseline sHER2 high level, the DCR in the sHER2 decrease in the negative group was higher than that in the continuous positive group (p=0.037). Patients with a rapid decline type of sHER2 dynamic change curve had higher ORR and prolonged TTP compared with patients with other types of sHER2 dynamic change curve. There is no correlation between OS and sHER2 levels. Conclusion: Our study showed that patients with advanced breast cancer had a high level of sHER2 at recurrence, regardless of whether they are tHER2 positive or negative. Dynamic detection of sHER2 can help predict therapeutic efficacy and prognosis, regardless of whether tHER-2 is positive or negative.

HDAC inhibitors target IRS4 to enhance anti­AR therapy in AR­positive triple­negative breast cancer.

Triple­negative breast cancer (TNBC) is the most malignant subtype of breast cancer. Androgen receptor (AR) has been identified as a potential therapeutic target for AR­positive TNBC; however, clinical trials have not yet produced an effective treatment. The present study aimed to identify a novel treatment regimen to improve the prognosis of AR­positive TNBC. First, a combination of an AR inhibitor (enzalutamide, Enz) and a selective histone deacetylase inhibitor (chidamide, Chid) was used to treat AR­positive TNBC cell lines, and a synergistic effect of these drugs was observed. The combination treatment inhibited cell proliferation and migration by arresting the cell cycle at the G2/M phase. Subsequently, next­generation sequencing was performed to detect changes in gene regulation. The results showed that the PI3K/Akt signalling pathway was significantly inhibited by the combination treatment of Enz and Chid. Gene Set Enrichment Analysis revealed that the combination group was significantly enriched in KRAS signalling. Analysis of the associated genes revealed that insulin receptor substrate 4 (IRS4) may have a critical role in blocking the activation of KRAS signalling. In a mouse xenograft model, combination treatment also inhibited the PI3K/Akt signalling pathway by upregulating the expression of IRS4 and thereby suppressing tumour growth. In conclusion, the results of the present study revealed that combination treatment with Enz and Chid can upregulate IRS4, which results in the blocking of KRAS signalling and suppression of tumour growth. It may be hypothesised that the expression levels of IRS4 could be used as a biomarker for screening patients with AR­positive TNBC using Enz and Chid combination therapy.

Three-dimensional echocardiography reveals early mitral valve alterations in hypertrophic cardiomyopathy genetic mutation carriers.

BACKGROUND: The mitral valve undergoes structural modifications in response to cardiac functional changes, often predating cardiac decompensation and overt clinical signs. Our study assessed the potential of mitral valve morphological changes as early indicators for detecting carriers of hypertrophic cardiomyopathy (HCM)-associated gene mutations. METHODS: We studied 505 participants: 189 without the pathogenic gene mutations and left ventricular hypertrophy (G-/LVH-), 149 carriers without LV hypertrophy (G+/LVH-), and 167 manifest HCM patients (G+/LVH+). We juxtaposed the mitral valve morphology and associated metrics across these groups, emphasizing those carrying MYH7 and MYBPC3 mutations. RESULTS: We discerned pronounced disparities in the mitral annulus and leaflet structures across the groups. The mitral valve apparatus in mutation carriers exhibited a tendency towards a flattened profile. Detailed analysis spotlighted MYBPC3 mutation carriers, whose mitral valves were notably flatter (with notably lower AHCWR values than non-carriers); this contrast was not evident in MYH7 mutation carriers. This mitral valve flattening, manifest in the mutation carriers, suggests it might be an adaptive response to incipient cardiac dysfunction in HCM's nascent stages. CONCLUSIONS: Three-dimensional echocardiography illuminates the initial mitral valve structural changes in HCM patients bearing pathogenic gene mutations. These morphological signatures hold promise as sensitive imaging markers, especially for asymptomatic carriers of the MYBPC3 mutation.

Gene-echocardiography: refining genotype-phenotype correlations in hypertrophic cardiomyopathy.

AIMS: This study aims to clarify the association between hypertrophic patterns and genetic variants in hypertrophic cardiomyopathy (HCM) patients, contributing to the advancement of personalized management strategies for HCM. METHODS AND RESULTS: A comprehensive evaluation of genetic mutations was conducted in 392 HCM-affected families using Whole Exome Sequencing. Concurrently, relevant echocardiographic data from these individuals were collected. Our study revealed an increased susceptibility to enhanced septal and interventricular septal thickness in HCM patients harbouring gene mutations compared with those without. Mid-septal hypertrophy was found to be associated predominantly with myosin binding protein C3 (MYBPC3) variants, while a higher septum-to-posterior wall ratio correlated with myosin heavy chain 7 (MYH7) variants. Mutations in MYH7, MYBPC3, and other sarcomeric or myofilament genes (troponin I3 [TNNI3], tropomyosin 1 [TPM1], and troponin T2 [TNNT2]) showed a relationship with increased hypertrophy in the anterior wall, interventricular septum, and lateral wall of the left ventricle. In contrast, alpha kinase 3 (ALPK3)-associated hypertrophy chiefly presented in the apical region, while hypertrophy related to titin (TTN) and obscurin (OBSCN) mutations exhibited a uniform distribution across the myocardium. Hypertrophic patterns varied with the type and category of gene mutations, offering valuable diagnostic insights. CONCLUSION: Our findings underscore a strong link between hypertrophic patterns and genetic variants in HCM, providing a foundation for more accurate genetic testing and personalized management of HCM patients. The novel concept of 'gene-echocardiography' may enhance the precision and efficiency of genetic counselling and testing in HCM.

The mixed subtype has a worse prognosis than other histological subtypes: a retrospective analysis of 217 patients with metaplastic breast cancer.

OBJECTIVE: Metaplastic breast cancer (MpBC) is an aggressive subtype of all breast cancer. We aimed to investigate the clinicopathological features, treatments and prognoses of MpBC patients. METHODS: We collected the data from MpBC patients diagnosed at Tianjin Medical University Cancer Hospital from 2010 to 2017. Kaplan Meier curves and Cox regression model were used to evaluating clinical outcomes and prognostic factors. After removing baseline differences by propensity score matching (PSM), we analyzed the prognosis between MpBC patients and invasive ductal carcinomas of no special type (IDC-NST) patients. RESULTS: A total of 217 MpBC patients were subsumed. Of all histological subtypes, 45.1% were mixed subtypes, followed by with mesenchymal differentiation (27.2%), pure squamous (15.2%) and pure spindle (12.4%) subtypes. 69.6% of MpBC were triple-negative, 25.3% and 6.5% were HR-positive and HER2-positive. MpBC patients had worse survival compared to IDC-NST patients, with 5-year RFS of 73.8 and 83.6% (HR = 1.177 95%CI (1.171-2.676) P = 0.0068), and 5-year BCSS of 79.0% and 89.7% (HR = 2.187 95%CI (1.357-3.523) P = 0.0013). In the multivariate COX model, AJCC stage, mixed subtype and chemotherapy were independent prognostic factors. Mixed MpBC is more aggressive than pure and with heterologous mesenchymal differentiation subtypes. And whether squamous or spindle MpBC, mixed forms have shorter outcomes than pure forms. CONCLUSIONS: MpBCs are associated with poorer prognoses than IDC-NSTs. They are heterogeneous with different clinicopathological features and clinical outcomes between histological subtypes. Pure and with heterologous mesenchymal differentiation subtypes have more survival benefits than the mixed subtype.

Development of a nomogram based on serum cytokine-related riskscore in breast cancer.

Background: Cytokines are involved in many inflammatory diseases and thus play an important role in tumor immune regulation. In recent years, researchers have found that breast cancer is not only related to genetic and environmental factors, but also to the chronic inflammation and immunity. However, the correlation between serum cytokines and blood tests indicators remain unclear. Methods: A total of 84 serum samples and clinicopathological data of breast cancer patients from Tianjin Cancer Institute & Hospital, Tianjin Medical University, Tianjin, P. R. China were collected. The expression levels of the 12 cytokines were detected by immunofluorescence method. Blood tests results were obtained from medical records. By stepwise Cox regression analysis, a cytokine-related gene signature was generated. Univariate and multivariate Cox regression were used to analyze the influence on the prognosis of patients. A nomogram was constructed to illustrate the cytokine-related riskscore predicting 5-year OS, which was further evaluated and validated by C-index and ROC curve. The correlation between the expression of cytokines in serum and other blood indicators was studied by using Spearman's test. Results: The riskscore was calculated as IL-4×0.99069 + TNF-α×0.03683. Patients were divided into high and low risk groups according to the median riskscore, with the high-risk group has a shorter survival time by log-rank test (training set, P=0.017; validation set, P=0.013). Combined with the clinical characteristics, the riskscore was found to be an independent factor for predicting the OS of breast cancer patients in both training cohort (HR=1.2, P<0.01) and validation cohort (HR=1.6, P=0.023). The 5-year C-index and AUC of the nomogram were 0.78 and 0.68, respectively. IL-4 was further found to be negatively correlated with ALB. Conclusion: In summary, we have developed a nomogram based on two cytokines including IL-4 and TNF-α to predict OS of breast cancer and investigated their correlation with blood test indicators.

Clinicopathological Features and Prognosis of Gastrointestinal Metastases From Breast Carcinoma: A Clinicopathological Study of 22 Patients.

Background. Breast carcinoma is the most common malignancy in women. Gastrointestinal metastasis is rarely found or diagnosed in patients with breast cancer. Methods. Clinicopathological features, treatment options, and prognosis were evaluated retrospectively for 22 patients with gastrointestinal metastases of breast carcinoma in Chinese women. Results. Presenting symptoms were non-specific: anorexia (21/22), epigastric pain (10/22), and vomiting (8/22), and 2 patients (2/22) presented with nonfatal hemorrhage. The first sites of metastases were skeleton (9/22), stomach (7/22), colorectal (7/22), lung (3/22), peritoneal (3/22), and liver (1/22). ER, PR, GATA binding protein 3 (GATA3), gross cystic disease fluid protein-15 (GCDFP-15), and keratin 7 can effectively confirm the diagnosis, especially in the case of keratin 20 negativity. Histology showed mainly ductal breast carcinoma (n = 11) was the predominant source of gastrointestinal metastases in this study, and lobular breast cancer (n = 9) accounted for a considerable proportion. The disease control rate to systemic therapy was 81% (17 of 21 treated patients), and the objective response rate was 10% (2 of 21 treated patients). Median overall survival was 71.5 months (range, 22-226 months), median survival for distant metastases was 23.5 months (range, 2-119 months) and the median survival for the time of gastrointestinal metastases diagnosis was 6 months (range, 2-73 months). Conclusions. Performing the endoscopy with biopsy was crucial for patients with any subtle gastrointestinal symptoms and a history of breast cancer. It is important to distinguish primary gastrointestinal carcinoma from breast metastatic carcinoma in order to select the optimal initial treatment and avoid unnecessary surgery.

Coupled Co-Doped MoS2 and CoS2 as the Dual-Active Site Catalyst for Chemoselective Hydrogenation.

Catalytic hydrogenation plays an important role in the industrial production of fine chemicals. Herein, we report a Co-doped MoS2 and CoS2 composite with a coupling interface and successfully apply it for the chemoselective hydrogenation of p-chloronitrobenzene to p-chloroaniline. The target catalyst 0.5CoMoS has ∼100% conversion and ∼100% selectivity. Experiments and theoretical calculations reveal that CoS2 is more favorable for adsorbing and activating H2 and provides active hydrogen (Ha) to Co-doped MoS2 by the coupling interface. By matching the production and consumption rates of Ha, the maximization of the reaction yield was achieved. This work may promote the study of MoS2-based catalysts for chemoselective hydrogenation.

Drug-induced liver injury in COVID-19 treatment: Incidence, mechanisms and clinical management.

The COVID-19 outbreak triggered a serious and potentially lethal pandemic, resulting in massive health and economic losses worldwide. The most common clinical manifestations of COVID-19 patients are pneumonia and acute respiratory distress syndrome, with a variety of complications. Multiple organ failure and damage, ultimately leading to patient death, are possible as a result of medication combinations, and this is exemplified by DILI. We hope to summarize DILI caused by the antiviral drugs favipiravir, remdesivir, lopinavir/ritonavir, and hydroxychloroquine in COVID-19 patients in this review. The incidence of liver injury in the treatment of COVID-19 patients was searched on PubMed to investigate DILI cases. The cumulative prevalence of acute liver injury was 23.7% (16.1%-33.1%). We discuss the frequency of these events, potential mechanisms, and new insights into surveillance strategies. Furthermore, we also describe medication recommendations aimed at preserving DILI caused by treatment in COVID-19 patients.

Case report: Camrelizumab associated with central retinal vein occlusion.

Immunotherapy has revolutionized cancer treatment and become one of the five pillars of cancer therapy. The clinical applications of immunotherapy have been adapted to range from the management of melanoma to most tumor types. As the clinical applications of cancer immunotherapies expand, understanding the treatment-related adverse events of these drugs becomes critical in clinical practice. We report a rare case of ocular immune-related side effects associated with camrelizumab that resulted in vision loss. A 56-year-old male patient was diagnosed with small cell lung cancer. The tumor involved the porta pulmonis and mediastinum upon initial diagnosis; therefore, surgery was not possible. Upon receiving the 10th immunotherapy session with camrelizumab 200 mg, the patient's visual acuity began to decrease in his right eye and a central retinal vein occlusion. Optical coherence tomography revealed significant cystoid exudation in the macular area and vitreous hemorrhage. The patient underwent vitrectomy, phacoemulsification and intraocular lens implantation after symptom onset. Following surgery, the patient's vision was limitedly restored. This is the first clinical report in China of central retinal vein occlusion and vitreous hemorrhage associated with anti-PD-1 therapy, ultimately leading to blindness. Although rare, clinical practitioners should be concerned about ocular adverse events associated with anti-PD-1 immunotherapy and develop a high index of suspicion for this possibility since ophthalmic manifestations that are rapidly detected, closely monitored, and appropriately managed are treatable.

Cardiac safety analysis of anti-HER2-targeted therapy in early breast cancer.

To evaluate the cardiac safety of anti-HER2-targeted therapy for early breast cancer; to investigate whether trastuzumab combined with pertuzumab increases cardiac toxicity compared with trastuzumab; to evaluate the predictive value of high-sensitivity Troponin (hs-TnI) and QTc for the cardiotoxicity associated with anti-HER2 targeted therapy in early breast cancer. A total of 420 patients with early-stage HER2-positive breast cancer who received trastuzumab or trastuzumab combined with pertuzumab for more than half a year in Tianjin Medical University Cancer Hospital from January 2018 to February 2021 were included. Left ventricle ejection fraction (LVEF), hs-TnI values, and QTc were measured at baseline and 3, 6, 9, 12 months. Cardiotoxicity was defined as a decrease in LVEF of at least 10 percentage points from baseline on follow-up echocardiography. Cardiotoxicity developed in 67 of the 420 patients (15.9%) and all patients had LVEF above 50% before and after treatment. The incidence of cardiotoxicity in trastuzumab and trastuzumab combined with pertuzumab was 14.3% and 17.9%, respectively (P > 0.05). Logistic regression analysis showed that age, coronary heart disease, left chest wall radiotherapy, and anthracyclines sequential therapy were independent risk factors for cardiotoxicity (P < 0.05). The value of hs-TnI and QTc at the end of treatment (12th month) were selected for ROC curve prediction analysis and the area under the ROC curve was 0.724 and 0.713, respectively, which was significantly different from the area of 0.5 (P < 0.05). The decrease of LVEF in the study was mostly asymptomatic, from the heart safety point of view, the anti-HER2 targeted therapy for early breast cancer was well tolerated. Trastuzumab combined with pertuzumab did not significantly increase cardiotoxicity. However, subgroup analysis suggests that in the presence of coronary artery disease (CAD) and sequential treatment with anthracene, trastuzumab and pertuzumab may increase the cardiac burden compared with trastuzumab. Hs-TnI and QTc may be useful in monitoring and predicting cardiotoxicity associated with anti-HER2 targeted therapy for early breast cancer.

Whole-genome bisulfite sequencing analysis of circulating tumour DNA for the detection and molecular classification of cancer.

BACKGROUND: Cancer cell-specific variation and circulating tumour DNA (ctDNA) methylation are promising biomarkers for non-invasive cancer detection and molecular classification. Nevertheless, the applications of ctDNA to the early detection and screening of cancer remain highly challenging due to the scarcity of cancer cell-specific ctDNA, the low signal-to-noise ratio of DNA variation, and the lack of non-locus-specific DNA methylation technologies. METHODS: We enrolled three cohorts of breast cancer (BC) patients from two hospitals in China (BC: n = 123; healthy controls: n = 40). We developed a ctDNA whole-genome bisulfite sequencing technology employing robust trace ctDNA capture from up to 200 µL plasma, mini-input (1 ng) library preparation, unbiased genome-wide coverage and comprehensive computational methods. RESULTS: A diagnostic signature comprising 15 ctDNA methylation markers exhibited high accuracy in the early (area under the curve [AUC] of 0.967) and advanced (AUC of 0.971) BC stages in multicentre patient cohorts. Furthermore, we revealed a ctDNA methylation signature that discriminates estrogen receptor status (Training set: AUC of 0.984 and Test set: AUC of 0.780). Different cancer types, including hepatocellular carcinoma and lung cancer, could also be well distinguished. CONCLUSIONS: Our study provides a toolset to generate unbiased whole-genome ctDNA methylomes with a minimal amount of plasma to develop highly specific and sensitive biomarkers for the early diagnosis and molecular subtyping of cancer.

Ado-trastuzumab emtansine in the treatment of lung adenocarcinoma with ERBB2 mutation: a case report and literature review.

The erb-b2 receptor tyrosine kinase 2 (ERBB2), also known as HER2, has long been recognized as an oncogenic driver in some breast and gastroesophageal cancers, and ERBB2-targeted therapies are standard for ERBB2-positive breast and gastric cancer. However, there are currently no standard therapies targeting the ERBB2 pathway in non-small cell lung cancer. Recently, somatic mutations in ERBB2 have been reported in 2-3% of patients with advanced lung adenocarcinoma, these mutations are trans-forming in lung cancer models and result in kinase activation, conferring some in-vitro sensitivity to trastuzumab. The ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate composed of trastuzumab joined via a stable linker to DM1. In this report, a 67-year-old male patient was diagnosed with advanced lung adenocarcinoma with multiple lymph node metastases, and multi-chemotherapy and immunotherapy were not effective. The results of genetic testing indicated a non-frameshift insertion mutation in exon 20 of the ERBB2 gene. The patients received T-DM1 at a dose of 3.6 mg/kg by intravenous infusion every 21 days until for 12 cycles. Partial response appeared in the tumor lesions after treatment for four cycles, and PET-computer tomography showed the tumor lesions were effectively controlled, and the efficacy evaluation was complete response after treatment for six cycles. Although the patient experienced second degree of thrombocytopenia during the treatment, the corresponding symptomatic treatment was taken, and the platelets could return to normal before the next cycle of T-DM1. Follow-up review showed the patient is in good health and the tumor has not recurred.

Gene Mutations Associated With Clinical Characteristics in the Tumors of Patients With Breast Cancer.

Background: Clinical characteristics including estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) are important biomarkers in the treatment of breast cancer, but how genomic mutations affect their status is rarely studied. This study aimed at finding genomic mutations associated with these clinical characteristics. Methods: There were 160 patients with breast cancer enrolled in this study. Samples from those patients were used for next-generation sequencing, targeting a panel of 624 pan-cancer genes. Short nucleotide mutations, copy number variations, and gene fusions were identified for each sample. Fisher's exact test compared each pair of genes. A similarity score was constructed with the resulting P-values. Genes were clustered with the similarity scores. The identified gene clusters were compared to the status of clinical characteristics including ER, PR, HER2, and a family history of cancer (FH) in terms of the mutations in patients. Results: Gene-by-gene analysis found that CCND1 mutations were positively correlated with ER status while ERBB2 and CDK12 mutations were positively correlated with HER2 status. Mutation-based clustering identified four gene clusters. Gene cluster 1 (ADGRA2, ZNF703, FGFR1, KAT6A, and POLB) was significantly associated with PR status; gene cluster 2 (COL1A1, AXIN2, ZNF217, GNAS, and BRIP1) and gene cluster 3 (FGF3, FGF4, FGF19, and CCND1) were significantly associated with ER status; gene cluster 2 was also negatively associated with a family history of cancer; and gene cluster 4 was significantly negatively associated with age. Patients were classified into four corresponding groups. Patient groups 1, 2, 3, and 4 had 24.1%, 36.5%, 38.7%, and 41.3% of patients with an FDA-recognized biomarker predictive of response to an FDA-approved drug, respectively. Conclusion: This study identified genomic mutations positively associated with ER and PR status. These findings not only revealed candidate genes in ER and PR status maintenance but also provided potential treatment targets for patients with endocrine therapy resistance.

Analysis of Clinical Characteristics, Treatment, and Prognostic Factors of 106 Breast Cancer Patients With Solitary Pulmonary Nodules.

OBJECTIVE: The clinical features of solitary pulmonary nodules (SPN) in breast cancer patients were retrospectively analyzed, and the clinical features of primary lung cancer (PLC) and metastatic pulmonary breast cancer (MBC) in breast cancer patients were compared, and the treatment plan, curative effect and influencing factors were analyzed. METHODS: The clinical data of 106 patients of SPN combined with breast cancer surgery in our hospital from January 2015 to June 2020 were analyzed. There were 65 patients of PLC and 41 patients of MBC. Record the characteristics of the primary breast cancer lesion in our patient, the interval between the initial diagnosis of breast cancer and the appearance of SPN, the previous treatment history of our patient, and the characteristics and surgical method of SPN. The survival status of all patients during the follow-up period was recorded. RESULTS: The onset age, interval, maximum nodule diameter, ER expression positive rate and radiotherapy history ratio of PLC patients were higher than those of MBC patients, and the lymph node positive rate and triple negative rate were lower than those of MBC patients (P < 0.05). Median survival was 51 months in patients with PLC and 37 months in patients with MBC. The 1, 3, and 5 year overall survival rates in patients with PLC were higher than those in patients with MBC (P < 0.05). Vascular tumor thrombus, SPN type and chemotherapy were all independent factors affecting the prognosis of patients with breast cancer combined with SPN (P < 0.05). CONCLUSION: PLC patients and MBC patients have significant differences in pathological characteristics, like the onset age, interval, maximum nodule diameter, ER expression positive rate, radiotherapy history ratio, the lymph node positive rate, and triple negative rate. Septum, vascular tumor thrombus, SPN type, and chemotherapy are all independent factors that affect the curative effect of breast cancer patients with SPN. Based on the nature of SPN, it can provide reference for clinicians to decide the treatment plan, improve patients' quality of life and prolong their survival time.

Chinese Medicinal Herb-Derived Carbon Dots for Common Diseases: Efficacies and Potential Mechanisms.

The management of hemorrhagic diseases and other commonly refractory diseases (including gout, inflammatory diseases, cancer, pain of various forms and causes) are very challenging in clinical practice. Charcoal medicine is a frequently used complementary and alternative drug therapy for hemorrhagic diseases. However, studies (other than those assessing effects on hemostasis) on charcoal-processed medicines are limited. Carbon dots (CDs) are quasi-spherical nanoparticles that are biocompatible and have high stability, low toxicity, unique optical properties. Currently, there are various studies carried out to evaluate their efficacy and safety. The exploration of using traditional Chinese medicine (TCM) -based CDs for the treatment of common diseases has received great attention. This review summarizes the literatures on medicinal herbs-derived CDs for the treatment of the difficult-to-treat diseases, and explored the possible mechanisms involved in the process of treatment.

Clinical significance and prognostic value of receptor conversion after neoadjuvant chemotherapy in breast cancer patients.

The hormone receptor (HR) status and human epidermal growth hormone receptor 2 (HER2) status of patients with breast cancer may change following neoadjuvant chemotherapy (NAC). We retrospectively analyzed the clinical data of 294 patients with stage II/III breast cancer to evaluate the clinical significance and prognostic value of receptor transformation after NAC in breast cancer patients. Pathological complete response after NAC was achieved in 10.7% of patients. HR, estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki-67 conversion rates were 9.2%, 6.5%, 13.0%, 4.4%, and 33.7%, respectively. Patients with stable HR (P = 0.01) and HER2 (P = 0.048) expression had more favorable overall survival (OS). Low or reduced Ki-67 expression was associated with better disease-free survival (DFS) (P < 0.001) and OS (P < 0.01). Multivariate analysis showed that the number of lymph nodes after NAC, HR conversion, and radiotherapy were independent prognostic factors for overall survival. HR conversion implied a higher risk of death [hazard ratio, 2.56 (95% confidence interval: 1.19-5.51); P = 0.016]. Patients with HR conversion after NAC who received endocrine therapy had better DFS (P = 0.674) and OS (P = 0.363) than those who did not receive endocrine therapy, even if the HR changed from positive to negative. In conclusion, pathological testing should be performed before and after NAC, and even patients with HR conversion after NAC might benefit from endocrine therapy.

Tolerance and Pharmacokinetics of Recombinant Human Endostatin Administered as Single-Dose or Multiple-Dose Infusions in Patients With Advanced Solid Tumors: A Phase I Clinical Trial.

Objective: This study aimed to investigate the tolerance and pharmacokinetic characteristics of recombinant human endostatin (rh-endostatin) administered as single-dose or multiple-dose infusions in patients with advanced solid tumors. Methods: This phase I trial was designed as a single-center, single-arm, nonrandomized, open-label, dose-escalation study. The trial consisted of 2 parts: a single-dose part and a multiple-dose part, each with 3 dose comparison groups. Rh-endostatin was administered as an intravenous injection only once at a dose of 5 mg/m2, 7.5 mg/m2, or 10 mg/m2 in the single-dose part and as a daily intravenous injection for 14 days at the same doses in the multiple-dose part. The serum pharmacokinetics, toxicity and immunogenicity of rh-endostatin were evaluated. Results: Dose-limiting toxicity (DLT) was not observed in any group. A few patients developed cardiotoxicity, such as QT prolongation or narrow arrhythmia. Other adverse events were slight coagulation abnormalities and haematological abnormalities. For rh-endostatin doses of 5 mg/m2, 7.5 mg/m2, and 10 mg/m2, the mean Cmax values in the single-dose part were 344 ± 38.7 ng/mL, 524 ± 157 ng/mL, and 800 ± 201 ng/mL, respectively, and the average AUC0-t values were 3290 ± 3790 ng•h/mL, 4940 ± 4380 ng•h/mL, and 5050 ± 3980 ng•h/mL, respectively. The Cmax ss values of the 3 doses in the multiple-dose part were 575 ± 270 ng/mL, 531 ± 106 ng/mL, and 864 ± 166 ng/mL, respectively, and the AUC0-τ values were 3610 ± 1040 ng•h/mL, 3290 ± 1090 ng•h/mL, and 5180 ± 1210 ng•h/mL, respectively. The Cmax of a single-dose regimen showed linear kinetic characteristics. The patients in the single-dose group were negative for serum antibodies against rh-endostatin, while one patient in the multiple-dose group was positive. Conclusions: Rh-endostatin as a daily intravenous injection for 14 days in patients with advanced solid tumors is safe and well tolerated, without DLT, at doses of 5 mg/m2, 7.5 mg/m2, and 10 mg/m2. Serum antibodies against rh-endostatin were very low after multiple infusions. For phase II trials, the recommended rh-endostatin dose is 10 mg/m2 as a daily intravenous injection for 14 days.

dNLR and TILS can be used as indicators for prognosis and efficacy evaluation of neo-adjuvant chemotherapy in breast cancer.

BACKGROUND: To explore the clinical value of dNLR and TILS in the prognostic diagnosis of breast cancer (BC) and the efficacy evaluation of neo-adjuvant chemotherapy. METHODS: From January 2012 to January 2014, 72 patients with BC who received neo-adjuvant chemotherapy in our hospital were selected for this study and analyzed retrospectively. The clinical value of dNLR and TILS in the prognosis of BC was observed, and the clinical data of the patients were collected for Cox regression analysis to observe their independent prognostic indicators. According to the clinical efficacy of neo-adjuvant chemotherapy, patients were divided into effective group (EG) (CR+PR) and invalid group (IG) (SD+PD), and the value of dNLR and TILS in the therapeutic effect of patients was observed. RESULTS: After therapy, there were 10 cases of CR, 44 cases of PR, 13 cases of SD and 5 cases of PD in 72 patients. With the improvement of curative effect, the expression of dNLR was gradually declined (P < 0.05). The less effective the patients were, the less TILS positive rate was (P < 0.05). However, the expression of dNLR in the EG was obviously lower than that in the IG (P < 0.05). The area under dNLR curve was 0.844, while the area under TILS curve was 0.618. Multivariate Cox regression analysis revealed that TNM staging, dNLR and TILS were independent prognostic factors that affected the patients. CONCLUSION: Patients with high expression of dNLR and TILS-negative BC have poor efficacy of neoadjuvant chemotherapy, and dNLR and TILS can be used as prognostic observation indexes for BC.

Cardiac angiosarcoma: A case report and review of the literature.

Primary cardiac tumors are extremely rare, among which malignancies comprise about 15-25%. As the most common type of primary cardiac malignancies, angiosarcomas tend to arise in the right heart, especially right atrium. In this case report, we presented a 32-year-old female with primary cardiac angiosarcoma in the right atrial appendage detected by transesophageal echocardiography, as it is difficult to display on conventional transthoracic echocardiography.