Publications by authors named "Yanxia Shi"

61 Publications

Impact of diabetes on promoting the growth of breast cancer.

Cancer Commun (Lond) 2021 Feb 20. Epub 2021 Feb 20.

Department of Molecular and Cellular Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.

Background: Type II diabetes mellitus (DM2) is a significant risk factor for cancers, including breast cancer. However, a proper diabetic breast cancer mouse model is not well-established for treatment strategy design. Additionally, the precise diabetic signaling pathways that regulate cancer growth remain unresolved. In the present study, we established a suitable mouse model and demonstrated the pathogenic role of diabetes on breast cancer progression.

Methods: We successfully generated a transgenic mouse model of human epidermal growth factor receptor 2 positive (Her2 or ERBB2) breast cancer with DM2 by crossing leptin receptor mutant (Lepr ) mice with MMTV-ErbB2/neu) mice. The mouse models were administrated with antidiabetic drugs to assess the impacts of controlling DM2 in affecting tumor growth. Magnetic resonance spectroscopic imaging was employed to analyze the tumor metabolism.

Results: Treatment with metformin/rosiglitazone in MMTV-ErbB2/Lepr mouse model reduced serum insulin levels, prolonged overall survival, decreased cumulative tumor incidence, and inhibited tumor progression. Anti-insulin resistance medications also inhibited glycolytic metabolism in tumors in vivo as indicated by the reduced metabolic flux of hyperpolarized C pyruvate-to-lactate reaction. The tumor cells from MMTV-ErbB2/Lepr transgenic mice treated with metformin had reprogrammed metabolism by reducing levels of both oxygen consumption and lactate production. Metformin decreased the expression of Myc and pyruvate kinase isozyme 2 (PKM2), leading to metabolism reprogramming. Moreover, metformin attenuated the mTOR/AKT signaling pathway and altered adipokine profiles.

Conclusions: MMTV-ErbB2/Lepr mouse model was able to recapitulate diabetic HER2 human breast cancer. Additionally, our results defined the signaling pathways deregulated in HER2 breast cancer under diabetic condition, which can be intervened by anti-insulin resistance therapy.
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http://dx.doi.org/10.1002/cac2.12147DOI Listing
February 2021

Postponing tumor onset and tumor progression can be achieved by alteration of local tumor immunity.

Cancer Cell Int 2021 Feb 10;21(1):97. Epub 2021 Feb 10.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, Guangdong, China.

Background: It has been known for years that the same genetic defects drive breast cancer formation, yet, the onset of breast cancer in different individuals among the same population differs greatly in their life spans with unknown mechanisms.

Methods: We used a MMTV-PyMT mouse model with different genetic backgrounds (FVB/NJ vs. C57BL/6J) to generate different cancer onset phenotypes, then profiled and analyzed the gene expression of three tumor stages in both Fvb.B6 and Fvb mice to explore the underlying mechanisms.

Results: We found that in contrast with the FVB/N-Tg (MMTV-PyMT) 634Mul mice (Fvb mice), mammary tumor initiation was significantly delayed and tumor progression was significantly suppressed in the Fvb.B6 mice (generated by crossing FVB/NJ with C57BL/6J mice). Transcriptome sequencing and analysis revealed that the differentially expressed genes were enriched in immune-related pathways. Flow cytometry analysis showed a higher proportion of matured dendritic cells in the Fvb.B6 mice. The plasma levels of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) were significantly reduced in the Fvb.B6 mice. IL-6 also impaired the maturation of bone marrow dendritic cells (BMDCs) of the Fvb mice in vitro.

Conclusion: All these findings suggest that immunity levels (characterized by a reduced IL-6 level and intact DC maturation in Fvb.B6 mice) are the key factors affecting tumor onset in a murine mammary cancer model.
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http://dx.doi.org/10.1186/s12935-021-01765-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874464PMC
February 2021

First Report of Cercospora Leaf Spot Caused by Cercospora cf. flagellaris on Okra in China.

Plant Dis 2021 Feb 10. Epub 2021 Feb 10.

Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing, No. 12, Zhongguancun Nandajie, Beijing, 100081, China, Beijing, China, 100081;

Okra [Abelmoschus esculentus (L.) Moench], which belongs to the family Malvaceae, is widely grown in the tropics, sub-tropics and warmer areas of the temperate zones for its immature seed pods which are consumed as a vegetable. In China, okra pods are consumed as not only vegetables but also as a traditional medicine to cure dental diseases and gastric ulcers. During September 2018 to June 2019, extensive spots on okra leaves were observed in several commercial fields (approximately 2.0 hectares), with disease incidence of approximately 25%~50% in the Yanqing District (115°98'E, 40°46'N) of Beijing, China. Symptoms of the disease initially appeared as small pale brown spots with yellow haloes. As the disease progressed, some spots gradually coalesced, forming larger irregular dark brown lesions. The centers of the lesions became grayish white. A total of 13 small fragments (3 to 5 mm) excised from the lesion margins were sterilized in 1% sodium hypochlorite (NaClO) for 1 min, followed by three washes with sterile distilled water, and then placed on potato dextrose agar (PDA) and incubated at 25°C in the dark for 5 days. In total, 21 cultures were obtained and purified by single-spore subcultures on PDA for morphological identification. The colonies on PDA were whitish to gray, with cottony aerial mycelium. Conidiophores were fasciculate, olivaceous brown, straight or geniculate, uniform in width, multiseptate, and ranged from 286/span> to 711 μm (avg. = 578 μm, n = 50). Conidia were hyaline, slightly curved or straight, needle shaped, truncate at the base, and terminal at the tip, 3-17-septate, and measuring 52 to 231 μm (avg. = 182 μm, n = 50). The morphological features were consistent with Cercospora cf. flagellaris Ellis & G. Martin (Groenewald et al. 2013). Pathogenicity tests were conducted on potted okra plants cv. 'Jiayuan'. Twenty four healthy okra plants at the true leaf stage were sprayed with conidial suspensions (1 × 106 conidia/mL), incubated at a glass cabinet maintained at 25°C and 90% relative humidity (RH). To each leaf approximately 10 mL of conidial suspension was applied. Plants sprayed with water were used as controls. Seven days later, dark brown spot, which were identical to those observed in the fields, were observed on inoculated leaves, whereas the control plants remained healthy. C. cf. flagellaris was reisolated from symptomatic leaves, confirming Koch's Postulates. Genomic DNA was extracted from fungal mycelium using the Plant Genomic DNA Kit (Tiangen Biotech Co. Ltd., Beijing, China). The nuclear ribosomal internal transcribed spacer region (ITS), and portions of the actin (ACT), histone H3 (HIS3), and translation elongation factor 1-α (TEF1) genes were amplified using primers ITS1/ITS4 (Groenewald et al. 2013), ACT-512F/ACT-783R (Carbone & Kohn 1999), CYLH3F/CYLH3R (Crous et al. 2006), and EF1-728F/EF1-986R (Carbone & Kohn 1999). The resulting 542 bp ITS, 226 bp ACT, 410 bp HIS3 and 306 bp TEF1 sequences of isolate QK14091813 were deposited in GeneBank (Accession nos. MT949700, MT949701, MT949702 and MT949703, respectively). The ITS, ACT, HIS3 and TEF1 sequences shared 99.42% to 100% identities to previously published sequences of C. cf. flagellaris (Accession nos. MN633275 for ITS, MF680960 for ACT, MK991295 for HIS3, and MK991292.1 for TEF1, respectively). Multi-locus phylogenetic analyses (ITS, ACT, HIS3, and TEF1) were performed by neighbor-joining method using MEGA 7.0. The resulting trees showed that C. cf. flagellaris isolate QK14091813 (this study) nested within the clade that includes other isolates of C. cf. flagellaris with a 99% confidence level. To our knowledge, this is the first report of C. cf. flagellaris causing leaf spot on okra (Farr and Rossman 2020). The pathogen has a worldwide distribution and an unusually broad host range, which can be of great significance, and the plant protection policy of priority to prevention and synthetical prevention should be followed.
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http://dx.doi.org/10.1094/PDIS-10-20-2155-PDNDOI Listing
February 2021

Safety, tolerability, and pharmacokinetics of BAT8001 in patients with HER2-positive breast cancer: An open-label, dose-escalation, phase I study.

Cancer Commun (Lond) 2021 Feb 2;41(2):171-182. Epub 2021 Feb 2.

Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, P. R. China.

Background: The introductions of anti- human epidermal growth factor receptor-2 (HER2) agents have significantly improved the treatment outcome of patients with HER2-positive breast cancer. BAT8001 is a novel antibody-drug conjugate targeting human epidermal growth factor receptor-2 (HER2)-expressing cells composed of a trastuzumab biosimilar linked to the drug-linker Batansine. This dose-escalation, phase I study was designed to assess the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of BAT8001 in patients with HER2-positive locally advanced or metastatic breast cancer.

Methods: This trial was conducted in subjects with histologically confirmed HER2-positive breast cancer (having evaluable lesions and an Eastern Cooperative Oncology Group performance status of 0 or 1) using a 3 + 3 design of escalating BAT8001 doses. Patients received BAT8001 intravenously in a 21-day cycle, with dose escalation in 5 cohorts: 1.2, 2.4, 3.6, 4.8, and 6.0 mg/kg. The primary objective was to evaluate the safety and tolerability of BAT8001. Preliminary activity of BAT8001 was also assessed as a secondary objective.

Results: Between March 2017 to May 2018, 29 HER2-positive breast cancer patients were enrolled. The observed dose-limiting toxicities were grade 4 thrombocytopenia and grade 3 elevated transaminase. The maximum tolerated dose was determined to be 3.6 mg/kg. Grade 3 or greater adverse events (AEs) occurred in 14 (48.3%) of 29 patients, including thrombocytopenia in 12 (41.4%) patients, aspartate aminotransferase increased in 4 (13.8%) patients, γ-glutamyl transferase increased in 2 (6.9%) patients, alanine aminotransferase increased in 2 (6.9%) patients, diarrhea in 2 (6.9%) patients. Objective response was observed in 12 (41.4%; 95% confidence interval [CI] = 23.5%-61.1%) and disease control (including patients achieving objective response and stable disease) was observed in 24 (82.8%; 95% CI = 64.2%-94.2%) patients.

Conclusions: BAT8001 demonstrated favorable safety profiles, with promising anti-tumor activity in patients with HER2-positive locally advanced or metastatic breast cancer. BAT8001 has the potential to provide a new therapeutic option in patients with metastatic HER2-positive breast cancer.
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http://dx.doi.org/10.1002/cac2.12135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896747PMC
February 2021

Floro-pyrazolo[3,4-d]pyrimidine derivative as a novel plant activator induces two-pathway immune system.

Phytochemistry 2021 Jan 15;184:112657. Epub 2021 Jan 15.

Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.

Plants are known to develop a multi-faceted innate immune system for pathogenic defense. Systemic acquired resistance (SAR) and induced systemic resistance (ISR) are the two main pathways. Many chemical inducers known as plant activators that activate innate immunity to defend against pathogens have been discovered. Currently, the exploitation of new plant activators is mainly done to develop analogs of salicylic acid as SAR-signaling molecules; however, the ISR pathway is hardly investigated for new plant activators. Based on recent studies on 1-methyl pyrazolo [3,4-d]pyrimidine bioactivity and ATP-induced resistance to biotrophic and necrotrophic pathogens, a new lead compound, 1-methyl-4-amino-pyrazolo [3,4-d]pyrimidine, was obtained as a new scaffold of plant activators for possible inducing ISR immunity system. Additionally, fluorine atom plays an important role in the design and development of new pesticides due to the unique physical chemistry effect, a series of pyrazolo [3,4-d]pyrimidine derivatives were designed and synthesized. Several compounds showed good broad-spectrum induced resistance in vivo, but there was no direct antibacterial activity in vitro. Notably, the introduction of fluorine atom at the para-position of the benzene ring greatly enhanced the induction activity of P1d both involved in SAR and ISR pathways, which implied the inducing resistance both in defending pathogens and insects.
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http://dx.doi.org/10.1016/j.phytochem.2021.112657DOI Listing
January 2021

First Report of Bacterial Leaf Spot of Cucurbita pepo Caused by Erwinia persicina in China.

Plant Dis 2020 Dec 21. Epub 2020 Dec 21.

Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing, No. 12, Zhongguancun Nandajie, Beijing, 100081, China, Beijing, China, 100081;

In February 2020, the common symptoms of water-soaked spots on Cucurbita pepo L. cotyledon were observed in Guangrao county in Shandong province, China. Field investigation showed that 40% of the Cucurbita pepo cotyledons in an area of approximately 0.8 ha were infected. The disease resulted in a severe loss in seedling production. Samples of C. pepo with water-soaked leaf spots were collected and prepared for pathogen analysis. Symptomatic cotyledon tissue was surface disinfested in 75% ethanol for 30 sec, then rinsed three times in sterilized water. Bacteria were released in sterile water in Petri dish for 2 min by cutting symptomatic tissue into small sections and stirring the plant tissue mixture fully. The diffusate was streaked onto plates containing nutrient agar (NA) and plates were incubated at 28℃ for 2 days. Three representative isolates were purified eventually from each of the plates. Colonies on NA were small, round and with smooth margins. All bacterial isolates characterized as gram-negative, white to cream color, and pink pigment was formed on the plates over long-term culture. The isolates were positive for catalase, Voges-Proskauer, potato rot, methyl red, acetoin production, nitrate utilization and citrate utilization, and acid production from maltose, glucose, melezitose, sucrose, D-arabinose, D-trehalose, cellobiose, lactose, raffinose, mannitol, D-sorbitol, melibiose and xylitol. KOH production was demonstrated according to strand formation within the potassium hydroxide test (Suslow et al. 1982). Isolates were negative for oxidase, arginine dihydrolase, phenylalanine deaminase, gelatinase, esculine, indole production and H2S production. Total genomic DNA was extracted from isolate XHL2002230201 with TIANamp Bacteria DNA Kit (TIANGEN). Universal primers 27F and 1492R (Monciardini et al. 2002) were used in PCR to amplify a 1,307-bp DNA fragment of the 16S rRNA region for molecular identification. Furthermore, four additional housekeeping genes (gyrB, atpD, rho, and rpoS) were selected and amplified using specially designed primers. The amplification products of 16S rRNA were sequenced and submitted to GenBank under accession number (MT568607.1). Sequence analysis showed 99% similarity to Erwinia persicina strains B57 (LM651373.1) and B64 (CI789_17875) by BLAST search in GenBank database (Gálvez et al. 2015; Cho et al. 2019). A phylogenetic tree was constructed, and the taxonomic position of strain XHL2002230201 was determined from the multilocus sequence analysis (MLSA) on 16S rRNA and other four housekeeping genes with E. persicina and not with other closely related Erwinia species. Pathogenicity tests and re-isolation and re-identification of the bacteria were performed to confirm the isolate and fulfill the Koch' postulates. The strain XHL2002230201 suspensions (108 CFU ml-1) were spray inoculated onto fifteen Cucurbita pepo seedlings with two true leaves, and the same number of control plants were inoculated with water. Experiments were repeated three times. All inoculated plants were kept in a moist chamber placed in a greenhouse at 28℃. Initial symptoms were observed on leaves of inoculated plants at 5 days post-inoculation, whereas no symptoms appeared on the plants inoculated with sterile distilled water. Based on morphological and biochemical characteristics, phylogenetic analysis, and Koch's postulates, the bacterial isolates were identified as E. persicina. To our knowledge, this is the first report of E. persicina causing leaf spot disease on Cucurbita pepo in China.
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http://dx.doi.org/10.1094/PDIS-06-20-1241-PDNDOI Listing
December 2020

Current management of chemotherapy-induced neutropenia in adults: key points and new challenges: Committee of Neoplastic Supportive-Care (CONS), China Anti-Cancer Association Committee of Clinical Chemotherapy, China Anti-Cancer Association.

Cancer Biol Med 2020 Nov 15;17(4):896-909. Epub 2020 Dec 15.

Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

Chemotherapy-induced neutropenia (CIN) is a potentially fatal and common complication in myelosuppressive chemotherapy. The timing and grade of CIN may play prognostic and predictive roles in cancer therapy. CIN is associated with older age, poor functional and nutritional status, the presence of significant comorbidities, the type of cancer, previous chemotherapy cycles, the stage of the disease, specific chemotherapy regimens, and combined therapies. There are many key points and new challenges in the management of CIN in adults including: (1) Genetic risk factors to evaluate the patient's risk for CIN remain unclear. However, these risk factors urgently need to be identified. (2) Febrile neutropenia (FN) remains one of the most common reasons for oncological emergency. No consensus nomogram for FN risk assessment has been established. (3) Different assessment tools [e.g., Multinational Association for Supportive Care in Cancer (MASCC), the Clinical Index of Stable Febrile Neutropenia (CISNE) score model, and other tools] have been suggested to help stratify the risk of complications in patients with FN. However, current tools have limitations. The CISNE score model is useful to support decision-making, especially for patients with stable FN. (4) There are still some challenges, including the benefits of granulocyte colony stimulating factor treatment and the optimal antibiotic regimen in emergency management of FN. In view of the current reports, our group discusses the key points, new challenges, and management of CIN.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721096PMC
November 2020

A Phase II Study of Fulvestrant 500 mg as Maintenance Therapy in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Patients with Advanced Breast Cancer After First-Line Chemotherapy.

Oncologist 2020 Nov 27. Epub 2020 Nov 27.

Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.

Lessons Learned: Fulvestrant 500 mg maintenance therapy showed a clinical benefit rate of 76% and median progression-free survival of 16.1 months in patients who achieved objective responses or disease control after first-line chemotherapy. Adverse events with fulvestrant maintenance therapy were consistent with the known safety profile of the drug.

Background: Evidence for maintenance hormonal therapy after chemotherapy for estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer is scarce. This study aimed to evaluate the efficacy of fulvestrant 500 mg maintenance therapy in patients after first-line chemotherapy.

Methods: We enrolled postmenopausal women with ER-positive/HER2-negative advanced breast cancer who attained tumor responses or disease control with four to eight cycles of chemotherapy as first-line treatment. Fulvestrant 500 mg was injected on days 1, 15, and 29 and every 28 (±3) days thereafter. The primary endpoint was the clinical benefit rate (CBR); the secondary endpoints included the objective response rate (ORR), progression-free survival (PFS), and safety.

Results: We included 58 patients; the median follow-up duration was 32.6 months. The CBR since commencing fulvestrant maintenance therapy was 76% (95% confidence interval [CI], 63%-86%), and ORR was 14% (95% CI, 6%-25%); eight patients achieved partial response. The median PFS for fulvestrant maintenance therapy was 16.1 months (95% CI, 10.3-21.0 months). Thirty-nine patients (67%) reported at least one adverse event, of which most were grade 1/2, whereas three patients (5%) reported grade 3 adverse events.

Conclusion: Fulvestrant 500 mg is a feasible and promising hormonal maintenance strategy in patients with ER-positive/HER2-negative advanced breast cancer who have no disease progression after first-line chemotherapy.
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http://dx.doi.org/10.1002/onco.13614DOI Listing
November 2020

First Report of Cercospora apiicola Causing Leaf Spots and Stem Lesions on Celery in China.

Plant Dis 2020 Nov 23. Epub 2020 Nov 23.

Institute of Vegetables and Flowers, Chinese Academy of Agricultural Science, Beijing, Beijing, China;

Celery (Apium graveolens L.) is a vegetable crop cultivated widely in the Mediterranean, Europe and parts of Asia. From March to May in 2014, leaf spots and stem lesions were observed on celery plants in Yanqing (116°03'E, 40°32'N), Beijing and Chengdu (104°06'E, 30°67'N), Sichuan Province. Plants developed 0.3-1.8 cm diameter subcircular leaf spots with brown centers surrounded by pale yellow halos. Spots on leaves were amphigenous. Necrotic areas on stems were subcircular to elongated, pale brown to brown. Plants in five greenhouses were surveyed with 30 to 60% disease incidence. Necrotic tissue from 8 stems and 12 leaves were cut from the margins of lesions and divided into two parts. One part was treated with lactophenol and used for microscopic examination. The other part was surface sterilized with 4% sodium hypochlorite for 2 min, rinsed three times in sterile water, placed onto 2% malt extract agar (MEA), and incubated at 26°C for seven days with natural daylight. Stromata on leaves and stems were not well developed. Four-to-ten conidiophores (15.3-56.5 × 2.8-5.5 μm) formed in fascicles, emerged through stomata or erupted through the cuticle. Conidia (n=50) were 60-135 × 2.5-4.5 μm, solitary, septate, cylindrical to obclavate-cylindrical, hila thickened and darkened. Colonies were white to smoke-gray, and aerial mycelia were sparse to moderate. Morphological characteristics of the pathogen were similar to Cercospora apiicola (Groenewald et al. 2006; Groenewald et al. 2013). The gDNA of 20 isolates was extracted from mycelium using the Plant Genomic DNA Kit (Tiangen, China). The internal transcribed spacers (ITS), actin (ACT), translation elongation factor 1-α (TEF1) and histone H3 (HIS3) regions were amplified with primer pairs ITS1/ITS4 (Groenewald et al. 2013), ACT-512F/ACT-783R (Carbone and Kohn 1999), EF1-728F/EF1-986R (Carbone and Kohn 1999), CYLH3F/CYLH3R (Crous et al. 2006). Phylogenetic analysis of multiple genes (Bakhshi et al. 2018) was conducted with the neighbor-joining method using MEGA7. The sequences of our isolate (QC14030702) and five published sequences of C. apiicola were clustered into one clade with a 99% confidence level. The sequences of QC14030702 have been deposited in GenBank with accessions KU870468 for ITS, KU870469 for ACT, KU870470 for TEF1, and KU870471 for HIS3. Pathogenicity of the isolates was tested on plants (cv. Jia Yuan Xi Yang Qin). Because the pathogen sporulated poorly on various media, mycelial fragments were sprayed on leaves in a suspension of 1×106 mL-1 in a greenhouse (temperature 26±0.5°C; RH 98%; photoperiod 12 h). Healthy plants were sprayed with sterilized water as controls. Three replicates of every isolate were conducted, and each replicate included 5 celery plants. After 7 days, leaf spots appeared on all inoculated plants, which were similar to those on celery in the field. All control plants remained asymptomatic. Re-isolation of the fungus from infected tissues showed same morphological and cultural characteristics of C. apiicola as the original isolates. C. apiicola has been reported in Greece, Korea, South Korea and Venezuela on celery, but never been reported in China (Farr and Rossman 2020). C. apiicola potential threatens celery production, and this the first report of the disease in China.
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http://dx.doi.org/10.1094/PDIS-09-20-1879-PDNDOI Listing
November 2020

Open-label, Multicenter, Phase II Study of RC48-ADC, a HER2-Targeting Antibody-Drug Conjugate, in Patients with Locally Advanced or Metastatic Urothelial Carcinoma.

Clin Cancer Res 2021 Jan 27;27(1):43-51. Epub 2020 Oct 27.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing, China.

Purpose: To evaluate the efficacy and safety of RC48-ADC, a novel humanized anti-HER2 antibody conjugated with monomethyl auristatin E, in patients with HER2 locally advanced or metastatic urothelial carcinoma (mUC) refractory to standard therapies.

Patients And Methods: This was a phase II, open-label, multicenter, single-arm study of patients with HER2 (IHC status 3+ or 2+) locally advanced or mUC who previously failed at least one line of systemic chemotherapy. The primary endpoint was the objective response rate (ORR) assessed by a blinded independent review committee (BIRC). The secondary endpoint included progression-free survival (PFS), disease control rate, duration of response, overall survival (OS), and safety.

Results: Forty-three patients were enrolled. The median follow-up was 20.3 months. The overall confirmed ORR as assessed by the BIRC was 51.2% [95% confidence interval (CI), 35.5%-66.7%]. Similar responses were observed in prespecified subgroups, such as those with liver metastasis and those previously treated with anti-programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) therapies. The median PFS and OS were 6.9 months (95% CI, 5.6-8.9) and 13.9 months (95% CI, 9.1-NE), respectively. The most common treatment-related adverse events (TRAE) were hypoesthesia (60.5%), alopecia (55.8%), and leukopenia (55.8%). Twenty-five (58%) patients experienced grade 3 TRAEs, including hypoesthesia (23.3%) and neutropenia (14.0%). No grade 4 or grade 5 TRAEs occurred.

Conclusions: RC48-ADC demonstrated a promising efficacy with a manageable safety profile in patients with HER2 locally advanced or mUC who had failed at least one line of systemic chemotherapy.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-2488DOI Listing
January 2021

Cavin3 Suppresses Breast Cancer Metastasis Inhibiting AKT Pathway.

Front Pharmacol 2020 30;11:01228. Epub 2020 Sep 30.

Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, United States.

Objective: Cavin3 is a putative tumor suppressor protein. However, its molecular action on tumor regulation is largely unknown. The aim of the current study is to explore the implication of cavin3 alteration, its clinical significance, and any potential molecular mechanisms in the regulation of breast cancer (BC).

Methods: TCGA (The Cancer Genome Atlas) and GTEx (Genotype-Tissue Expression) data bases, and 17 freshly paired BC and adjacent normal tissues were analyzed for mRNA levels of . Furthermore, cavin3 protein expression from 407 primary BC samples were assessed by immunohistochemistry (IHC) and measured by H-score. The clinical significance of cavin3 expression was explored by Kaplan-Meier analysis and the Cox regression method. biological assays were performed to elucidate the function and underlying mechanisms of cavin 3 in BC cell lines.

Results: mRNA was dramatically down-regulated in BC compared with the negative control. The median H-score of cavin3 protein by IHC was 50 (range 0-270). There were 232 (57%) and 175 (43%) cases scored as low (H-score≤50) and high (H-score >50) levels of cavin3, respectively. Low cavin3 was correlated with a higher T and N stage, and worse distant metastasis-free survival (DMFS) and overall survival (OS). Multivariate survival analysis revealed low cavin3 was an independent fact for worse DMFS. In BC cells, an overexpression of cavin3 could inhibit cell migration and invasion, and significantly decreased the level of p-Akt. Knockout of cavin3, meanwhile, promoted cell invasion ability and increased the level of p-AKT.

Conclusion: Cavin3 expression is significantly lower in BC and is correlated with distant metastasis and worse survival. Cavin3 functions as a metastasis suppressor inhibiting the AKT pathway, suggesting cavin3 as a potential prognostic biomarker and a target for BC treatment.
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http://dx.doi.org/10.3389/fphar.2020.01228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556234PMC
September 2020

Aerosol transmission of Pseudomonas amygdali pv. lachrymans in greenhouses.

Sci Total Environ 2020 Dec 1;748:141433. Epub 2020 Aug 1.

Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing 100081, China. Electronic address:

Most previous studies on aerosols have focused on the role of aerosols in the transmission of human and animal pathogens; however, little is known about the role of aerosols in the transmission of plant bacterial disease. In this study, experimental evidence for the emission and transmission of Pseunomonas. amygdali pv. lachrymans (Pal) aerosol was provided, and the results supported that diseased cucumber plants served as the main source of Pal aerosol. Bacterial aerosols released by infected plants played a significant role in the epidemiology of cucumber angular leaf spot (ALS) disease. Aerosol chambers were constructed to study the characteristics of Pal aerosols released by artificially infested cucumber plants. The particle size of Pal aerosol was predominately distributed from 1.1 to 4.7 μm, accounting for 72.16% of the total amount of Pal aerosol. The infection threshold of aerosolized Pal to cause ALS disease was 84-179 CFU/m. In addition, the transmission dynamics of Pal aerosols from donor cucumber plants to recipient cucumber plants were also confirmed in exposure chambers and greenhouses. The results from the present study verified the hypothesis that aerosol dissemination is a potential route for the epidemiology of plant bacterial disease, and these data will contribute to the development of new strategies for the effective alleviation and control of plant bacterial diseases.
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http://dx.doi.org/10.1016/j.scitotenv.2020.141433DOI Listing
December 2020

Adjuvant chemotherapy for small, lymph node-negative, triple-negative breast cancer: A single-center study and a meta-analysis of the published literature.

Cancer 2020 Aug;126 Suppl 16:3837-3846

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Background: Current guidelines recommend adjuvant chemotherapy for patients with small, lymph node-negative, triple-negative breast cancer (TNBC) measuring >5 mm (T1b disease), but clinical evidence to support this recommendation is lacking. Thus, the current study aimed to evaluate the survival benefit of adjuvant chemotherapy in patients with T1N0M0 (measuring ≤2 cm) TNBC with different tumor sizes.

Methods: The authors retrospectively evaluated consecutive patients with pT1N0M0 TNBC who were diagnosed between 2000 and 2016 at Sun Yat-Sen University Cancer Center. For the meta-analysis, electronic medical databases were searched for all relevant studies regarding the effect of adjuvant chemotherapy on the target population.

Results: Of the 351 enrolled patients, 309 (88%) received adjuvant chemotherapy and 42 patients (12%) did not. The distribution by T classification was T1a in 19 patients (5.4%), T1b in 67 patients (19.1%), and T1c in 265 patients (75.5%). Adjuvant chemotherapy significantly improved recurrence-free survival (RFS) in the patients with T1c disease, but not those with T1b and T1a disease. Meanwhile, there was no difference in RFS noted according to the chemotherapy regimen among patients with T1c disease. Seven eligible studies comprising 1525 patients with T1N0M0 (941 with T1a/bN0M0) were included in the meta-analysis. The meta-analysis demonstrated that adjuvant chemotherapy significantly reduced the rate of disease recurrence for patients with T1a/b disease as a group, but the population driving that was only patients with T1b disease, not those with T1a disease.

Conclusions: Although the retrospective analysis demonstrated a survival benefit of adjuvant chemotherapy only for patients with T1cN0 TNBC, the meta-analysis showed it also is beneficial for individuals with T1bN0 TNBC. For patients with T1cN0M0 TNBC, less intensive chemotherapy regimens achieve an excellent survival outcome similar to that of intensive anthracycline and taxane combination chemotherapy.
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http://dx.doi.org/10.1002/cncr.32878DOI Listing
August 2020

Metronomic chemotherapy of cyclophosphamide plus methotrexate for advanced breast cancer: Real-world data analyses and experience of one center.

Cancer Commun (Lond) 2020 05 11;40(5):222-233. Epub 2020 May 11.

Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China.

Background: Real-world data of the CM regimen [cyclophosphamide (CTX) plus methotrexate (MTX)] in metronomic pattern for advanced breast cancer is limited to small-sample or retrospective studies. This study was aimed to determine the effectiveness and safety of CM regimen in treating advanced breast cancer and to identify which patients are most likely to benefit from metronomic CM regimen.

Methods: Patients with advanced breast cancer who received the metronomic CM regimen at least once between January 2009 and February 2019 in Sun Yat-sen University Cancer Center were included. Clinicopathological characteristics were collected. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier estimates. Characteristics between patients with PFS < 6 months and ≥6 months were compared using the Chi-square test. Univariate and multivariate Cox regression model was used to estimate the prognostic factors for PFS and OS.

Results: A total of 186 patients were included. The median age and follow-up were 49 years and 13.3 months, respectively. Over 50% of the patients were estrogen receptor/progesterone receptor-positive, and 60.8% had been heavily treated (≥3 lines). The objective response rate was 3.8%, the disease control rate at 12 weeks was 41.4%, and the clinical benefit rate at 24 weeks was 31.2% (58/186). The median PFS was 4.0 months [95% confidence interval (CI): 3.6-4.7 months], the median duration of clinical benefit was 9.5 months (95% CI: 8.2-10.8 months), and the median OS was 26.8 months (95% CI: 20.9-37.7 months). Multivariate analysis for PFS revealed the CM regimen as maintenance therapy and no liver metastasis as favorable prognostic factors. Furthermore, patients without liver metastasis were more likely to have a PFS over 6 months than those with liver involvement (P = 0.022). Liver, lymph node, and brain metastases were unfavorable prognostic factors for OS. The CM regimen was well-tolerated without newly reported adverse events.

Conclusions: The CM regimen was effective in selected patients. In clinical practice, it would be better used as maintenance therapy and in patients without liver metastasis. Further follow-up investigation should be performed to examine its effect when used in combination with other treatments and determine predictive biomarkers.
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http://dx.doi.org/10.1002/cac2.12029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238669PMC
May 2020

Efficacy of Moxifloxacin plus Treatment of Physician's Choice in Patients with Metastatic Breast Cancer.

Oncologist 2020 10 1;25(10):e1439-e1445. Epub 2020 Jun 1.

Department of Medical Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.

Lessons Learned: Moxifloxacin plus continuation of the previous treatment of physician's choice shows promising efficacy in patients with metastatic breast cancer. The addition of moxifloxacin shows well-tolerated toxicities.

Background: Recent studies have confirmed bacterial infection as an important contributor in cancer. Elimination of tumor-associated microbes may lead to a reduction in tumors and improved survival. Moxifloxacin is an orally administrated fourth-generation quinolone with broad-spectrum coverage against tumor-associated bacteria.

Methods: In this study, we assessed the efficacy and safety of moxifloxacin in combination with treatment of physician's choice (TPC) in patients with metastatic breast cancer (MBC). In this single-arm, phase II study, we recruited 30 patients with MBC who had a trend toward disease progression (stable disease [SD] with increased tumor size) during TPC before enrollment at Sun Yat-sen University Cancer Center between January 1 and July 30, 2018. Eligible patients were given moxifloxacin once daily at a dose of 400 mg from days 1 to 7 of a 28-day cycle, in addition to continuing to receive the therapy previously selected by their physicians. Tumor response was determined according to RECIST (version 1.1). Progression-free survival (PFS) was calculated using the Kaplan-Meier method.

Results: The concomitant use of moxifloxacin and previous TPC yielded a median PFS of 6.6 months (95% confidence interval [CI]: 4.0-9.1) and a 1-year PFS of 25.9% (95% CI: 10.0%-41.9%). Objective responses were achieved in seven (23.3%, 95% CI: 7.3%-39.4%) patients. The clinical benefit rate was 46.7% (95% CI: 27.7%-65.6%). No grade 4 adverse events (AEs) and four grade 3 AEs were observed, none of which were considered to have definite relation to moxifloxacin.

Conclusion: The combination of moxifloxacin with previous TPC shows promising efficacy and well-tolerated toxicities in patients with MBC.
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http://dx.doi.org/10.1634/theoncologist.2020-0364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543292PMC
October 2020

Whole-genome analysis of ZF2, a biocontrol agent that protects against leaf spot diseases.

3 Biotech 2020 Apr 30;10(4):186. Epub 2020 Mar 30.

Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing, 100081 China.

spp. have been widely described for their potentials to protect plants against pathogens. Here, we reported the whole genome sequence of ZF2, which was isolated from the stem of a healthy cucumber plant. Strain ZF2 showed a broad spectrum of antagonistic activities against many plant bacterial and fungal pathogens, including the cucumber leaf spot fungus The complete genome of ZF2 contained a 3,931,418-bp circular chromosome, with an average G + C content of 46.50%. Genome comparison revealed closest similarity between ZF2 and other strains. Genes homologous to 14 gene clusters for biosynthesis of secondary metabolites were identified in the ZF2 genome. Also identified were a number of genes involved in bacterial colonization, including the genes for motility, biofilm formation, flagella biosynthesis, and capsular biosynthesis. Numerous genes associated with plant-bacteria interactions, including cellulase or protease biosynthesis, and plant growth promotion were also identified in the ZF2 genome. Overall, our data will aid future studies of the biocontrol mechanisms of ZF2 and promote its application in vegetable disease control.
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http://dx.doi.org/10.1007/s13205-020-2165-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105517PMC
April 2020

The complete genome sequence of Rahnella aquatilis ZF7 reveals potential beneficial properties and stress tolerance capabilities.

Arch Microbiol 2020 Apr 9;202(3):483-499. Epub 2019 Nov 9.

Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing, 100081, China.

Rahnella aquatilis ZF7 is a plant beneficial strain isolated from Sakura tree soil with potential for biocontrol. Here, we present the complete genome sequence of R. aquatilis ZF7, which consists of one 4.49 Mb circular chromosome and a 54-kb plasmid named pRAZF7. Phylogenetic analyses revealed that R. aquatilis ZF7 is much similar to the strains Rahnella sp. Y9602 and R. aquatilis HX2 than others evaluated. In this study, multiple genes encoding functions that likely contribute to plant growth promotion, biocontrol and stress tolerance were identified by comparative genome analyses, including IAA production, phosphate solubilization, antibiotic resistance and formation of Se nanoparticles (SeNPs). In addition, these functions were also confirmed by in vitro experiments. Considering its ability to form SeNPs, strain R. aquatilis ZF7 will contribute to nano-agriculture. Overall, the features of R. aquatilis ZF7 make it a high potential and competitive strain in biocontrol, and the genome data will help further studies on the mechanisms of plant growth promotion and biocontrol.
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http://dx.doi.org/10.1007/s00203-019-01758-1DOI Listing
April 2020

Author's Reply to Puértolas-Tena and Pérez-Surio: "Efficacy and Safety of Supportive Care Biosimilars Among Cancer Patients: A Systematic Review and Meta-Analysis".

BioDrugs 2019 10;33(5):585-588

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.

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http://dx.doi.org/10.1007/s40259-019-00379-wDOI Listing
October 2019

Correction to: Efficacy and Safety of Supportive Care Biosimilars Among Cancer Patients: A Systematic Review and Meta‑Analysis.

BioDrugs 2019 10;33(5):589-594

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.

The authors unintentionally included in the meta-analysis both the initial abstract and the final paper of the study by Puertolas et al. [45, 48]. In order to remove this duplication, the following corrections are required.
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http://dx.doi.org/10.1007/s40259-019-00378-xDOI Listing
October 2019

Bicalutamide plus Aromatase Inhibitor in Patients with Estrogen Receptor-Positive/Androgen Receptor-Positive Advanced Breast Cancer.

Oncologist 2020 01 21;25(1):21-e15. Epub 2019 Aug 21.

Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.

Lessons Learned: Studies targeting the androgen receptor (AR) signaling pathway in aromatase inhibitor (AI)-resistant breast cancer are limited. Bicalutamide, one of the commonly used AR inhibitors in prostate cancer, in combination with AI, did not show synergistic activity in patients with estrogen receptor-positive and AI-resistant disease in this phase II, single-arm study. The clinical benefit rate and objective response rate at 6 months were 16.7% and 0%, respectively, and the study was terminated after the first stage.

Background: Endocrine resistance is a major problem in clinical practice. Studies have shown that androgen receptor (AR) signaling activation may be one of the mechanisms, and targeting AR showed some promising results in AR-positive triple-negative breast cancer. The aim of this study was to assess the efficacy and safety of bicalutamide plus another aromatase inhibitor in patients with nonsteroidal aromatase inhibitor (AI) or steroidal AI resistance and estrogen receptor (ER)-positive and AR-positive advanced breast cancer.

Methods: A Simon's two-stage, phase II, single-arm study was conducted. We assumed the clinical benefit rate (CBR) of 40% would be significant in clinical practice. In this case, if ≥4 patients of the 19 patients in the first stage benefited from treatment, the CBR would achieve the assumed endpoint. If fewer than four patients benefited from treatment in the first stage, the trial would be terminated. All patients received bicalutamide 50 mg per day orally plus another aromatase inhibitor. The primary outcome was CBR; secondary outcomes included objective response rate (ORR), progression-free survival (PFS), and tolerability.

Results: A total of 19 patients enrolled in the first stage, and 18 patients met all criteria for analysis. The trial terminated according to protocol after the first stage. After a median follow-up of 14 months, the CBR at 6 months was 16.7% (3/18); no patients with partial or complete response were observed. The median PFS was 2.7 months. Bicalutamide in combination with AI was well tolerated.

Conclusion: Bicalutamide in combination with another AI did not show synergistic activity in patients with ER-positive breast cancer and AI resistance. Results suggest that no more large-sample clinical trials should be conducted in this population for overcoming endocrine resistance.
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http://dx.doi.org/10.1634/theoncologist.2019-0564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964139PMC
January 2020

Comparative genomic analysis of Pectobacterium carotovorum subsp. brasiliense SX309 provides novel insights into its genetic and phenotypic features.

BMC Genomics 2019 Jun 13;20(1):486. Epub 2019 Jun 13.

Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing, 100081, China.

Background: Pectobacterium carotovorum subsp. brasiliense is a broad host range bacterial pathogen, which causes blackleg of potatoes and bacterial soft rot of vegetables worldwide. Production of plant cell wall degrading enzymes is usually critical for Pectobacterium infection. However, other virulence factors and the mechanisms of genetic adaptation still need to be studied in detail.

Results: In this study, the complete genome of P. carotovorum subsp. brasiliense strain SX309 isolated from cucumber was compared with eight other pathogenic bacteria belonging to the Pectobacterium genus, which were isolated from various host plants. Genome comparison revealed that most virulence genes are highly conserved in the Pectobacterium strains, especially for the key virulence determinants involved in the biosynthesis of extracellular enzymes and others including the type II and III secretion systems, quorum sensing system, flagellar and chemotactic genes. Nevertheless, some variable regions of the T6SS and the CRISP-Cas immune system are unique for P. carotovorum subsp. brasiliense.

Conclusions: The extensive comparative genomics analysis revealed highly conserved virulence genes in the Pectobacterium strains. However, several variable regions of type VI secretion system and two subtype Cas mechanism-Cas immune systems possibly contribute to the process of Pectobacterium infection and adaptive immunity.
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http://dx.doi.org/10.1186/s12864-019-5831-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567464PMC
June 2019

Efficacy and Safety of Anti-cancer Biosimilars Compared to Reference Biologics in Oncology: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BioDrugs 2019 Aug;33(4):357-371

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.

Background: Many biosimilars of monoclonal antibodies (mAbs) are becoming increasingly available as anticancer therapies, such as the rituximab, bevacizumab, and trastuzumab biosimilars. However, no comprehensive summary of their efficacy and safety is available.

Objective: This study synthesized current evidence on the efficacy and safety of mAb biosimilars relative to their reference biologics among cancer patients.

Methods: We searched PubMed, Embase, the Cochrane library, ClinicalTrials.gov, the ISI Web of Science, and several Chinese databases from their inception dates to December 31, 2018, for randomized controlled trials (RCTs) or comparative observational studies that compared the efficacy and safety of biosimilars with reference biologics used in oncology. The binary outcomes were pooled using risk ratio (RR) with 95% confidence intervals (CIs), continuous outcomes using weighted mean difference (WMD) with 95% CIs, and time-to-event outcomes using hazard ratios (HRs). Subgroup and sensitivity analyses were conducted following this. We used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach to rate the quality of the evidence.

Results: We did not find any comparative observational studies that fit the criteria. Twenty-three RCTs were identified for biosimilars of three mAbs, of which eight RCTs examined rituximab biosimilars (total N = 1534), six RCTs were for bevacizumab biosimilars (total N = 1897), and nine were for trastuzumab biosimilars (total N = 4953), respectively. The quality of the GRADE evidence for efficacy and safety outcomes was moderate or low. The findings were robust for all pre-specified subgroup and sensitivity analyses.

Conclusion: The existing evidence suggests highly comparable efficacy and safety profiles between mAb biosimilars and their reference biologics in oncological drugs.
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http://dx.doi.org/10.1007/s40259-019-00358-1DOI Listing
August 2019

Efficacy and Safety of Supportive Care Biosimilars Among Cancer Patients: A Systematic Review and Meta-Analysis.

BioDrugs 2019 08;33(4):373-389

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.

Background: Biologics are widely used to manage the side effects of cancer treatment (e.g., epoetin alfa is used to treat chemotherapy-induced anemia [CIA] and granulocyte colony-stimulating factors [G-CSFs] are used to treat chemotherapy-induced neutropenia [CIN]). As several patents for biologics used in cancer treatment have expired, a number of companies have developed supportive care biosimilars (e.g., epoetin alfa biosimilar, filgrastim biosimilar, pegfilgrastim biosimilar).

Objective: The objective of this study was to synthesize current evidence on the efficacy and safety of supportive care biosimilars compared with their reference biologics in oncology.

Methods: We searched PubMed, Embase, the Cochrane library, ClinicalTrials.gov, ISI Web of Science and several Chinese databases from their inception dates to December 31, 2018 for randomized controlled trials (RCTs) or comparative observational studies that compared the efficacy and safety of supportive care biosimilars and their reference biologics in oncology. We pooled results separately for RCTs and observational studies, as such studies involve different patient populations and are designed differently. We pooled binary outcomes using risk ratios (RR) with confidence intervals (CIs) and continuous outcomes using weighted mean differences (WMD) with 95% CIs, then conducted subgroup and sensitivity analyses. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the quality of evidence.

Results: We identified 28 studies that compared biosimilars of G-CSF or epoetin alfa: one RCT and five cohort studies (total N = 2816) of epoetin alfa biosimilars, and 13 RCTs and 9 cohort studies (total N = 23,043) of G-CSF biosimilars [corrected]. Despite involving different populations, RCTs and observational studies comparing biosimilars and reference biologics indicated similar efficacy and safety results. Overall, there was no statistically significant difference in any efficacy or safety outcomes between any biosimilars and their corresponding original biologics (all p > 0.05). The quality of GRADE evidence of efficacy and safety outcomes was moderate or low. Findings were robust for all prespecified subgroup and sensitivity analyses.

Conclusion: Existing evidence suggests highly comparable efficacy and safety profiles for supportive care biosimilars and their reference biologics in oncology.
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http://dx.doi.org/10.1007/s40259-019-00356-3DOI Listing
August 2019

The Effects of Ganglioside-Monosialic Acid in Taxane-Induced Peripheral Neurotoxicity in Patients with Breast Cancer: A Randomized Trial.

J Natl Cancer Inst 2020 01;112(1):55-62

Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.

Background: Taxane-induced peripheral neuropathy (TIPN) is a dose-limiting adverse effect. Ganglioside-monosialic acid (GM1) functions as a neuroprotective factor. We assessed the effects of GM1 on the prevention of TIPN in breast cancer patients.

Methods: We conducted a randomized, double-blind, placebo-controlled trial including 206 patients with early-stage breast cancer planning to receive taxane-based adjuvant chemotherapy with a follow-up of more than 1 year. Subjects were randomly assigned to receive GM1 (80 mg, day -1 to day 2) or placebo. The primary endpoint was the Functional Assessment of Cancer Treatment Neurotoxicity subscale score after four cycles of chemotherapy. Secondary endpoints included neurotoxicity evaluated by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 and the Eastern Cooperative Oncology Group neuropathy scale. All statistical tests were two-sided.

Results: In 183 evaluable patients, the GM1 group reported better mean Functional Assessment of Cancer Treatment Neurotoxicity subscale scores than patients in the placebo group after four cycles of chemotherapy (43.27, 95% confidence interval [CI] = 43.05 to 43.49 vs 34.34, 95% CI = 33.78 to 34.89; mean difference = 8.96, 95% CI = 8.38 to 9.54, P < .001). Grade 1 or higher peripheral neurotoxicity in Common Terminology Criteria for Adverse Events v4.0 scale was statistically significantly lower in the GM1 group (14.3% vs 100.0%, P < .001). Additionally, the GM1 group had a statistically significantly lower incidence of grade 1 or higher neurotoxicity assessed by Eastern Cooperative Oncology Group neuropathy scale sensory neuropathy (26.4% vs 97.8%, P < .001) and motor neuropathy subscales (20.9% vs 81.5%, P < .001).

Conclusions: The treatment with GM1 resulted in a reduction in the severity and incidence of TIPN after four cycles of taxane-containing chemotherapy in patients with breast cancer.
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http://dx.doi.org/10.1093/jnci/djz086DOI Listing
January 2020

CDK4/6 inhibitor palbociclib enhances the effect of pyrotinib in HER2-positive breast cancer.

Cancer Lett 2019 04 21;447:130-140. Epub 2019 Jan 21.

Sun Yat-Sen University Cancer Center, The State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, PR China. Electronic address:

Human epidermal growth factor receptor 2 (HER2) is amplified in about 20% breast cancers. Treat of HER2 positive breast cancers has been greatly promoted in last few years, but the accompany HER2 blockade has hindered the therapeutic effect. Pyrotinib is a pan-HER kinase inhibitor that suppresses signaling through the RAS/RAF/MEK/MAPK and PI3K/AKT pathways. Palbociclib is a CDK4/6 inhibitor that inhibits cell cycle progression and cancer cell proliferation in ER+ breast cancers. We hypothesized that the combination of pan-HER kinase inhibitors and CDK4/6 inhibitors would show synergistic antitumor activity in vivo in vitro. Our data show that a combination of palbociclib and pyrotinib was highly synergistic in inhibiting cancer proliferation and colony formation. The combined treatment also induced significant decreases in pAKT and pHER3 activation, induced G0-G1 cell cycle arrest, and increased rates of apoptosis. In the xenograft model, the combination treatment demonstrated greater antitumor activity than either agent alone, with no apparent increase in toxicity. Our results offer a preclinical rationale clinical investigation of the effectiveness of a combination treatment of palbociclib with pyrotinib for breast cancer treatment.
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http://dx.doi.org/10.1016/j.canlet.2019.01.005DOI Listing
April 2019

Occurrence, Distribution, and Characteristics of Boscalid-Resistant Corynespora cassiicola in China.

Plant Dis 2019 Jan 19;103(1):69-76. Epub 2018 Nov 19.

Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing, 100081, China.

Corynespora blight, caused by Corynespora cassiicola (Berk. & M.A. Curtis) C.T. Wei, has become an important disease affecting cucumber in China. Its management mainly depends on fungicides; however, no research has been conducted to assess the sensitivity of C. cassiicola in China to boscalid, a succinate dehydrogenase inhibitor (SDHI). To facilitate boscalid resistance monitoring, baseline sensitivity was established. The EC value (i.e., the concentration that results in 50% mycelial growth inhibition) frequency distribution was unimodal with a right-hand tail; with the means 0.95 ± 0.51 μg/ml and the range 0.03 to 2.85 μg/ml. We then assessed the sensitivity of C. cassiicola to boscalid using discriminatory doses and EC values. In total, 27.8% of the 798 isolates were resistant, distributed in five provinces and two municipalities. Thirty-seven isolates with different resistance levels to boscalid were also evaluated for their sensitivity to carboxin, fluopyram, and penthiopyrad. Seven SDHI resistance patterns were observed (i.e., I: BosFluoPenCar; II: BosFluoPenCar; III: BosFluoPenCar; IV: BosFluoPenCar; V: BosFluoPenCar; VI: BosFluoPenCar; and VII: BosFluoPen Car, VHR: very highly resistant; HR: highly resistant; MR: moderately resistant; LR: low resistant; R: resistant; SS: supersensitive), corresponding to seven mutations in sdhB/C/D genes, respectively.
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http://dx.doi.org/10.1094/PDIS-11-17-1760-REDOI Listing
January 2019

An assessment of prognostic immunity markers in breast cancer.

NPJ Breast Cancer 2018 29;4:35. Epub 2018 Oct 29.

5Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC USA.

Tumor-infiltrating lymphocytes (TIL) and immunity gene signatures have been reported to be significantly prognostic in breast cancer but have not yet been applied for calculation of risk of recurrence in clinical assays. A compact set of 17 immunity genes was derived herein from an Affymetrix-derived gene expression dataset including 1951 patients (AFFY1951). The 17 immunity genes demonstrated significant prognostic stratification of estrogen receptor (ER)-negative breast cancer patients with high proliferation gene expression. Further analysis of blood and breast cancer single-cell RNA-seq datasets revealed that the 17 immunity genes were derived from TIL that were inactive in the blood and became active in tumor tissue. Expression of the 17 immunity genes was significantly ( < 2.2E-16,  = 91) correlated with TILs percentage on H&E in triple negative breast cancer. To demonstrate the impact of tumor immunity genes on prognosis, we built a Cox model to incorporate breast cancer subtypes, proliferation score and immunity score (72 gene panel) with significant prediction of outcomes ( < 0.0001,  = 1951). The 72 gene panel and its risk evaluation model were validated in two other published gene expression datasets including Illumina beads array data METABRIC ( < 0.0001,  = 1997) and whole transcriptomic mRNA-seq data TCGA ( = 0.00019,  = 996) and in our own targeted RNA-seq data TARGETSEQ ( < 0.0001,  = 303). Further examination of the 72 gene panel in single cell RNA-seq of tumors demonstrated tumor heterogeneity with more than two subtypes observed in each tumor. In conclusion, immunity gene expression was an important parameter for prognosis and should be incorporated into current multi-gene assays to improve assessment of risk of distant metastasis in breast cancer.
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http://dx.doi.org/10.1038/s41523-018-0088-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206135PMC
October 2018

Pretreatment anti-Mullerian hormone-based nomogram predicts menstruation status after chemotherapy for premenopausal women with hormone receptor-positive early breast cancer.

Breast Cancer Res Treat 2019 Feb 3;173(3):619-628. Epub 2018 Nov 3.

Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Dongfeng Road East 651#, Guangzhou, 510060, China.

Purpose: Ovarian function is important for optimizing endocrine treatment in patients with hormone receptor-positive (HR+) early breast cancer (eBC). The aim of the study was to determine whether patients' pretreatment levels of anti-Mullerian hormone (AMH) were associated with menses status after chemotherapy and to build a predictive nomogram model for amenorrhea in women with HR+ eBC.

Methods: Between August 2013 and December 2014, 120 premenopausal patients with HR+ eBC were included retrospectively. The associations among age, prechemotherapy levels of AMH, follicle-stimulating hormone (FSH),and estradiol (E2) and the 2-year postchemotherapy menses status were analyzed. We determined the cutoff values of hormone levels by using the biostatistical tool (Cutoff Finder). A novel nomogram was established to predict the 2-year amenorrhea status based on the logistic analysis. Concordance index (C-index) was used to validate the capacity.

Results: One hundred nine women (90.8%) experienced amenorrhea after chemotherapy. AMH < 0.965 ng/ml predicted amenorrhea at 2 years (AUC 0.84, sensitivity 74% and specificity 81.8%), independent of age. The predictive nomogram based on age and pretreatment AMH and FSH levels was developed to predict the probability of 2-year postchemotherapy amenorrhea with a C-index of 0.88 (95% CI 0.84-0.91).

Conclusions: In premenopausal patients with HR+ eBC, prechemotherapy AMH concentration was associated with the patient's 2-year amenorrhea status, independent of age. The nomogram model based on age and pretreatment AMH and FSH levels accurately predicted the 2-year amenorrhea status.
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http://dx.doi.org/10.1007/s10549-018-4997-2DOI Listing
February 2019

Comparative genomic analysis of Pseudomonas amygdali pv. lachrymans NM002: Insights into its potential virulence genes and putative invasion determinants.

Genomics 2019 12 15;111(6):1493-1503. Epub 2018 Oct 15.

Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing 100081, China. Electronic address:

Pseudomonas amygdali pv. lachrymans is currently of important plant pathogenic bacteria that causes cucumber angular leaf spot worldwide. The pathogen has been studied for its roles in pathogenicity and plant inheritance resistance. To further delineate traits critical to virulence, invasion and survival in the phyllosphere, we reported the first complete genome of P. amygdali pv. lachrymans NM002. Analysis of the whole genome in comparison with three closely-related representative pathovars of P. syringae identified the conservation of virulence genes, including flagella and chemotaxis, quorum-sensing systems, two-component systems, and lipopolysaccharide and antiphagocytosis. It also revealed differences of invasion determinants, such as type III effectors, phytotoxin (coronatine, syringomycin and phaseolotoxin) and cell wall-degrading enzyme, which may contribute to infectivity. The aim of this study was to derive genomic information that would reveal the probable molecular mechanisms underlying the virulence, infectivity and provide a better understanding of the pathogenesis of the P. syringae pathovars.
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http://dx.doi.org/10.1016/j.ygeno.2018.10.004DOI Listing
December 2019

Erratum to: Variation of cassiicolin genes among Chinese isolates of Corynespora cassiicola.

J Microbiol 2018 Sep;56(9):691

Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing, 10081, P. R. China.

In the online published article by Wu et al. since 30 July 2018, the figure 4 is unfortunately incorrect. The figure 4 should be corrected as below.
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http://dx.doi.org/10.1007/s12275-018-8580-7DOI Listing
September 2018