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Breast Cancer Herceptin

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https://www.readbyqxmd.com/read/27858859/risk-factors-of-trastuzumab-induced-cardiotoxicity-in-breast-cancer-a-meta-analysis
#1
Zeeshan Jawa, Ruth M Perez, Lydia Garlie, Maharaj Singh, Rubina Qamar, Bijoy K Khandheria, Arshad Jahangir, Yang Shi
BACKGROUND: Trastuzumab targets the human epidermal growth factor receptor 2 oncogene and in combination with first-line therapy results in significantly improved survival outcomes and has thus become standard of care in both adjuvant and metastatic settings. While it is estimated that 1% to 4% of patients treated with trastuzumab will develop heart failure and ∼10% will experience a reduction in left ventricular ejection fraction (LVEF), the patient risk factors associated with trastuzumab-induced cardiotoxicity (TIC) are unclear...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27815036/crispr-mediated-targeting-of-her2-inhibits-cell-proliferation-through-a-dominant-negative-mutation
#2
Huajing Wang, William Sun
With the discovery of the CRISPR/Cas9 technology, genome editing could be performed in a rapid, precise and effective manner. Its potential applications in functional interrogation of cancer-causing genes and cancer therapy have been extensively explored. In this study, we demonstrated the use of the CRISPR/Cas9 system to directly target the oncogene HER2. Directing Cas9 to exons of the HER2 gene inhibited cell growth in breast cancer cell lines that harbor amplification of the HER2 locus. The inhibitory effect was potentiated with the addition of PARP inhibitors...
November 1, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27813707/development-and-preclinical-studies-of-64-cu-nota-pertuzumab-f-ab-2-for-imaging-changes-in-tumor-her2-expression-associated-with-response-to-trastuzumab-by-pet-ct
#3
Karen Lam, Conrad Chan, Raymond M Reilly
We previously reported that microSPECT/CT imaging with (111)In-labeled pertuzumab detected decreased HER2 expression in human breast cancer (BC) xenografts in athymic mice associated with response to treatment with trastuzumab (Herceptin). Our aim was to extend these results to PET/CT by constructing F(ab')2 of pertuzumab modified with NOTA chelators for complexing (64)Cu. The effect of the administered mass (5-200 µg) of (64)Cu-NOTA-pertuzumab F(ab')2 was studied in NOD/SCID mice engrafted with HER2-positive SK-OV-3 human ovarian cancer xenografts...
November 4, 2016: MAbs
https://www.readbyqxmd.com/read/27770268/sensitizing-effect-of-juglone-is-mediated-by-down-regulation-of-notch1-signaling-pathway-in-trastuzumab-resistant-skbr3-cells
#4
Soraya Sajadimajd, Razieh Yazdanparast
Trastuzumab (Herceptin) monoclonal antibody directed against HER2 receptor has been administered as a treatment for metastatic HER2 positive breast cancer. The problematic issue in treatment of HER2 positive breast cancer cells is commonly the induction of resistance to trastuzumab which might be due to modulation of some vital signaling elements such as Notch1 and Pin1. In this study, we were aimed to investigate whether the cross talk between pin1 and Notch1 has a role in this event. Our results indicated that the expression level of Pin1 in resistant SKBR3 cells increased by about twofold relative to sensitive SKBR3 cells...
October 21, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27749791/possible-efficacy-of-topical-dorzolamide-in-the-treatment-of-paclitaxel-related-cystoid-macular-edema
#5
Rahul Dwivedi, Sambath Tiroumal
PURPOSE: Paclitaxel (Taxol) is a microtubule-stabilizing agent and belongs to the taxane group of chemotherapeutic drugs. It is used to treat numerous malignancies, such as breast and lung cancers. A rare side effect of this drug includes cystoid macular edema (CME), which is presumed to resolve after cessation of Paclitaxel. We present a case of topical Dorzolamide 2% (Trusopt) having a possible successful effect in the treatment of Paclitaxel-related nonresolving CME. By highlighting this rare ocular side effect of a common chemotherapeutic agent, which fails to resolve upon cessation of the drug alone, we suggest a possible treatment that may help other ophthalmologists in their management of similar cases...
October 4, 2016: Retinal Cases & Brief Reports
https://www.readbyqxmd.com/read/27730538/budget-impact-analysis-of-biosimilar-trastuzumab-for-the-treatment-of-breast-cancer-in-croatia
#6
August Cesarec, Robert Likić
BACKGROUND AND OBJECTIVE: Breast cancer is the most common cancer in women and has considerable impact on healthcare budgets and patients' quality of life. Trastuzumab (Herceptin(®)) is a monoclonal antibody directed against the human epidermal growth factor receptor (HER2) for the treatment of breast cancer. Several trastuzumab biosimilars are currently in development. In 2015, trastuzumab was the drug with the highest financial consumption among all drugs in Croatia. This model estimates the 1-year budget impact of the introduction of biosimilar trastuzumab in Croatia...
October 11, 2016: Applied Health Economics and Health Policy
https://www.readbyqxmd.com/read/27726101/lapatinib-resistance-in-her2-cancers-latest-findings-and-new-concepts-on-molecular-mechanisms
#7
Huiping Shi, Weili Zhang, Qiaoming Zhi, Min Jiang
In the era of new and mostly effective molecular targeted therapies, human epidermal growth factor receptor 2 positive (HER2+) cancers are still intractable diseases. Lapatinib, a dual epidermal growth factor receptor (EGFR) and HER2 tyrosine kinase inhibitor, has greatly improved breast cancer prognosis in recent years after the initial introduction of trastuzumab (Herceptin). However, clinical evidence indicates the existence of both primary unresponsiveness and secondary lapatinib resistance, which leads to the failure of this agent in HER2+ cancer patients...
October 10, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27721408/cytoplasmic-gper-translocation-in-cancer-associated-fibroblasts-mediates-camp-pka-creb-glycolytic-axis-to-confer-tumor-cells-with-multidrug-resistance
#8
T Yu, G Yang, Y Hou, X Tang, C Wu, X-A Wu, L Guo, Q Zhu, H Luo, Y-E Du, S Wen, L Xu, J Yin, G Tu, M Liu
Multiple drug resistance is a challenging issue in the clinic. There is growing evidence that the G-protein-coupled estrogen receptor (GPER) is a novel mediator in the development of multidrug resistance in both estrogen receptor (ER)-positive and -negative breast cancers, and that cancer-associated fibroblasts (CAFs) in the tumor microenvironment may be a new agent that promotes drug resistance in tumor cells. However, the role of cytoplasmic GPER of CAFs on tumor therapy remains unclear. Here we first show that the breast tumor cell-activated PI3K/AKT (phosphoinositide 3-kinase/AKT) signaling pathway induces the cytoplasmic GPER translocation of CAFs in a CRM1-dependent pattern, and leads to the activation of a novel estrogen/GPER/cAMP/PKA/CREB signaling axis that triggers the aerobic glycolysis switch in CAFs...
October 10, 2016: Oncogene
https://www.readbyqxmd.com/read/27714776/trastuzumab-cardiotoxicity-from-clinical-trials-to-experimental-studies
#9
REVIEW
Balazs T Nemeth, Zoltan V Varga, Wen Jin Wu, Pal Pacher
Epidermal growth factor receptor-2 (HER-2) is overexpressed in 20 to 25% of human breast cancers, which is associated with aggressive tumour growth and poor prognosis. Trastuzumab (Herceptin®) is a humanized monoclonal antibody directed against HER-2, the first highly selective form of therapy targeting HER-2 overexpressing tumours. Although initial trials indicated high efficacy and a favourable safety profile of the drug, the first large, randomized trial prompted a retrospective analysis of cardiac dysfunction in earlier trials utilizing trastuzumab...
October 7, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27686050/herceptin-functionalized-pure-paclitaxel-nanocrystals-for-enhanced-delivery-to-her2-postive-breast-cancer-cells
#10
Jin-Ki Noh, Muhammad Naeem, Jiafu Cao, Eun Hee Lee, Min-Soo Kim, Yunjin Jung, Jin-Wook Yoo
The objective of this study was to prepare Herceptin (HCT)-functionalized paclitaxel nanocrystals and evaluated their cell-specific interactions, cellular accumulation, and growth inhibition in HER2-positve breast cancer cells as a tumor-targeted delivery module. Paclitaxel (PTX) was fabricated in the form of nanocrystals (PNCs) by a sono-precipitation method, and HCT were coated using a facile non-covalent method (PNCs-HCT). Our results showed that the PNCs-HCT were stable for at least 1month at 4°C with no noticeable desorption of HCT...
September 26, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27669438/cxcr4-inhibitors-could-benefit-to-her2-but-not-to-triple-negative-breast-cancer-patients
#11
S Lefort, A Thuleau, Y Kieffer, P Sirven, I Bieche, E Marangoni, A Vincent-Salomon, F Mechta-Grigoriou
The CXCR4 receptor and its ligand CXCL12 (also named stromal cell-derived factor 1, SDF1) have a critical role in chemotaxis and homing, key steps in cancer metastasis. Although myofibroblasts expressing CXCL12 are associated with the presence of axillary metastases in HER2 breast cancers (BC), the therapeutic interest of targeting CXCR4/CXCL12 axis in the different BC subtypes remains unclear. Here, we investigate this question by testing antitumor activity of CXCR4 inhibitors in patient-derived xenografts (PDX), which faithfully reproduce human tumor properties...
September 26, 2016: Oncogene
https://www.readbyqxmd.com/read/27635041/commentary-on-recombinant-humanized-anti-her2-antibody-herceptin-enhances-the-antitumor-activity-of-paclitaxel-and-doxorubicin-against-her2-neu-overexpressing-human-breast-cancer-xenografts-a-follow-up
#12
https://www.readbyqxmd.com/read/27632934/gene-therapy-using-plasmid-dna-encoded-anti-her2-antibody-for-cancers-that-overexpress-her2
#13
H Kim, S N Danishmalik, H Hwang, J-I Sin, J Oh, Y Cho, H Lee, M Jeong, S-H Kim, H J Hong
Plasmid DNA-encoded antibodies, or DNA-based monoclonal antibodies (dMAbs), are delivered by intramuscular injection and in vivo electroporation (EP) and are effective in virus neutralization, although they have not been evaluated for tumor gene therapy. Here we investigated whether a dMAb was appropriate for tumor gene therapy. We constructed the expression plasmids coding for the heavy or light chain of a parental murine antibody of Herceptin with the antibody genes codon- and RNA-optimized and fused to the Kozak-IgE leader sequence in pVax1...
October 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27628098/global-longitudinal-strain-a-useful-everyday-measurement
#14
A King, J Thambyrajah, E Leng, M J Stewart
Herceptin (Trastuzumab) is a widely used and effective drug for the treatment of Her2+ breast cancer but its cardiotoxic side effects require regular monitoring by echocardiography. A 10% reduction in left ventricular ejection fraction can lead to suspension of treatment and therefore has significant implications for patient prognosis in terms of cardiac and cancer outcomes. Assessment of LV function by conventional 2D biplane method of discs (2DEF) has limitations in accuracy and reproducibility. Global longitudinal strain (GLS) is becoming more widely available and user friendly...
September 2016: Echo Research and Practice
https://www.readbyqxmd.com/read/27617041/subgroup-based-adaptive-suba-designs-for-multi-arm-biomarker-trials
#15
Yanxun Xu, Lorenzo Trippa, Peter Müller, Yuan Ji
Targeted therapies based on biomarker profiling are becoming a mainstream direction of cancer research and treatment. Depending on the expression of specific prognostic biomarkers, targeted therapies assign different cancer drugs to subgroups of patients even if they are diagnosed with the same type of cancer by traditional means, such as tumor location. For example, Herceptin is only indicated for the subgroup of patients with HER2+ breast cancer, but not other types of breast cancer. However, subgroups like HER2+ breast cancer with effective targeted therapies are rare and most cancer drugs are still being applied to large patient populations that include many patients who might not respond or benefit...
June 2016: Statistics in Biosciences
https://www.readbyqxmd.com/read/27539136/challenges-of-treating-incidental-synchronous-bilateral-breast-cancer-with-differing-tumour-biology
#16
Jonathan Walter Esclovon, Melissa Ponder, Nail Aydin, Subhasis Misra
A 59-year-old woman with right breast mass was diagnosed with invasive ductal carcinoma (IDC). Workup consisted of bilateral diagnostic mammogram and ultrasound (US); both showed a right breast mass with normal left breast. Core biopsy showed IDC with estrogen receptor negative (ER-)/progesterone receptor negative (PR-) and HER2/neu positive receptor status. The patient underwent carboplatin-based chemotherapy with Herceptin. The mass completely resolved. The patient desired to proceed with bilateral total mastectomy with right sentinel lymph node biopsy (SLNB)...
August 18, 2016: BMJ Case Reports
https://www.readbyqxmd.com/read/27533001/in-vitro-detection-of-human-breast-cancer-cells-sk-br3-using-herceptin-conjugated-liquid-crystal-microdroplets-as-a-sensing-platform
#17
Wang Ding, Kailash Chandra Gupta, Soo-Young Park, Young-Kyoo Kim, Inn-Kyu Kang
The present study utilizes antibody-protein interactions to develop an LC microdroplet based biosensor for naked eye detection of SK-BR3 human breast cancer cells. The herceptin antibody-conjugated LC microdroplets were fabricated using 4-cyano-4'-pentyl biphenyl (5CB) as the liquid crystalline phase and sodium dodecyl sulfate (SDS) as the surfactant. The poly (styrene-b-acrylic acid) amphiphilic block copolymer (PS-b-PA) played a role as a modifier for the liquid crystalline interfaces. The 5CB molecules in the herceptin antibody-conjugated LC microdroplets have shown an orientation transition from radial to bipolar on selective interactions with targeted SK-BR3 breast cancer cells, which are over expressed by the human epidermal growth factor receptor 2-positive (HER2)...
October 20, 2016: Biomaterials Science
https://www.readbyqxmd.com/read/27526618/her2-immunohistochemical-evaluation-by-traditional-microscopy-and-by-digital-analysis-and-the-consequences-for-fish-testing
#18
Thomas Marcuzzo, Fabiola Giudici, Elisa Ober, Clara Rizzardi, Cristina Bottin, Fabrizio Zanconati
AIM: Her2 protein is the key marker determining the choice of Herceptin therapy after a diagnosis of breast cancer. Its evaluation is made in most laboratories by immunohistochemistry, and interpreted by a pathologist using an optical microscope, a process subject to inter-observer variability, particularly for samples scored as equivocal (2+). Software analysis products have been introduced, seeking to reduce this variability. In this study, we compared the results of both traditional evaluation and a specific software package (VISIA Imaging) to those from fluorescent in situ hybridization (FISH)...
August 2, 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/27367271/comparison-of-three-different-conjugation-strategies-in-the-construction-of-herceptin-bearing-paclitaxel-loaded-nanoparticles
#19
Kongtong Yu, Yulin Zhou, Yuhuan Li, Xiangshi Sun, Fengying Sun, Xinmei Wang, Hongyan Mu, Jie Li, Xiaoyue Liu, Lesheng Teng, Youxin Li
Research on quantitatively controlling the ligand density on the surface of nanocarriers is in the frontier and becomes a technical difficulty for targeted delivery system designing. In this study, we developed an improved pre-conjugation (Imp) strategy, in which herceptin as a ligand was pre-conjugated with DSPE-PEG2000-Mal via chemical cross-linking, followed by conjugation onto the surface of pre-prepared paclitaxel-loaded PLGA/DODMA nanoparticles (PDNs) through hydrophobic interaction and electrostatic attraction for paclitaxel delivery...
August 19, 2016: Biomaterials Science
https://www.readbyqxmd.com/read/27357488/therapeutic-potential-and-critical-analysis-of-trastuzumab-and-bevacizumab-in-combination-with-different-chemotherapeutic-agents-against-metastatic-breast-colorectal-cancer-affecting-various-endpoints
#20
REVIEW
Mohd Wahid, Raju K Mandal, Sajad A Dar, Arshad Jawed, Mohtashim Lohani, Mohammad Y Areeshi, Naseem Akhter, Shafiul Haque
Researchers are working day and night across the globe to eradicate or at least lessen the menace of cancer faced by the mankind. The two very frequently occurring cancers faced by the human beings are metastatic breast cancer and metastatic colorectal cancer. The various chemotherapeutic agents like anthracycline, cyclophosphamide, paclitaxel, irinotecan, fluorouracil and leucovorin etc., have been used impressively for long. But the obstinate character of metastatic breast cancer and metastatic colorectal cancer needs more to tackle the threat...
August 2016: Critical Reviews in Oncology/hematology
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