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https://www.readbyqxmd.com/read/28732370/silibinin-an-old-drug-for-hematological-disorders
#1
REVIEW
Hai Zou, Xing-Xing Zhu, Guo-Bing Zhang, Yuan Ma, Yi Wu, Dong-Sheng Huang
Silibinin (silybin), a non-toxic natural polyphenolic flavonoid, is the principal and the most biologically active component of silymarin. It is efficient in the treatment of acute and chronic liver disorders caused by toxins, drug, alcohol, hepatitis, and gall bladder disorders. Further, in our previous studies, we explored the anti-cancer efficacy in common cancers, such as lung, prostatic, colon, breast, bladder, as well as, hepatocellular carcinoma. Interestingly, silibinin is still not solely limited to the treatment of these diseases...
July 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28725493/interferon-alpha-based-immunotherapies-in-the-treatment-of-b-cell-derived-hematologic-neoplasms-in-today-s-treat-to-target-era
#2
REVIEW
Li Zhang, Yu-Tzu Tai, Matthew Zhi Guang Ho, Lugui Qiu, Kenneth C Anderson
B cell lymphoma and multiple myeloma (MM) are the most common hematological malignancies which benefit from therapeutic monoclonal antibodies (mAbs)-based immunotherapies. Despite significant improvement on patient outcome following the use of novel therapies for the past decades, curative treatment is unavailable for the majority of patients. For example, the 5-year survival of MM is currently less than 50%. In the 1980s, interferon-α was used as monotherapy in newly diagnosed or previously treated MM with an overall response rate of 15-20%...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28724539/racial-and-ethnic-disparities-in-hematologic-malignancies
#3
Kedar Kirtane, Stephanie J Lee
Racial and ethnic disparities in patients with solid malignancies have been well documented. Less is known about these disparities in patients with hematologic malignancies. With the advent of novel chemotherapeutics and targeted molecular, cellular, and immunologic therapies, it is important to identify differences in care that may lead to disparate outcomes. This review provides a critical appraisal of the empirical research on racial and ethnic disparities in incidence, survival, and outcomes in patients with hematologic malignancies...
July 19, 2017: Blood
https://www.readbyqxmd.com/read/28720126/a-small-molecule-cytokine-combination-enhances-hematopoietic-stem-cell-proliferation-via-inhibition-of-cell-differentiation
#4
Lan Wang, Xin Guan, Huihui Wang, Bin Shen, Yu Zhang, Zhihua Ren, Yupo Ma, Xinxin Ding, Yongping Jiang
BACKGROUND: Accumulated evidence supports the potent stimulating effects of multiple small molecules on the expansion of hematopoietic stem cells (HSCs) which are important for the therapy of various hematological disorders. Here, we report a novel, optimized formula, named the SC cocktail, which contains a combination of three such small molecules and four cytokines. METHODS: Small-molecule candidates were individually screened and then combined at their optimal concentration with the presence of cytokines to achieve maximum capacity for stimulating the human CD34(+) cell expansion ex vivo...
July 18, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28716814/potency-matched-dual-cytokine-antibody-fusion-proteins-for-cancer-therapy
#5
Roberto De Luca, Alex Soltermann, Francesca Pretto, Catherine Pemberton-Ross, Giovanni Pellegrini, Sarah Wulhfard, Dario Neri
A novel biopharmaceutical, consisting of the F8 monoclonal antibody (specific to a splice isoform of fibronectin) simultaneously fused to both tumor necrosis factor and interleukin-2, was found to react with the majority of solid tumors and hematological malignancies in mouse and man, but not with healthy adult tissues. The product selectively localized to neoplastic lesions in vivo, as evidenced by quantitative biodistribution studies using radioiodinated protein preparations. When the potency of the cytokine payloads was matched by a single-point mutation, the resulting fusion protein (IL2-F8-TNF(mut)) eradicated soft-tissue sarcomas in immunocompetent mice, which did not respond to individual antibody-cytokine fusion proteins or by standard doxorubicin treatment...
July 17, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28716013/long-term-renal-survival-of-%C3%AE-3-heavy-chain-deposition-disease-a-case-report
#6
Takayuki Katsuno, Shige Mizuno, Masatsuna Mabuchi, Naotake Tsuboi, Atsushi Komatsuda, Shoichi Maruyama
BACKGROUND: Monoclonal immunoglobulin deposition disease (MIDD) is characterized by the non-amyloid deposition of monoclonal immunoglobulin fragments in the basement membranes. Heavy chain deposition disease (HCDD) is a type of MIDD. HCDD is an extremely rare disease, and only three cases have been reported in Japan up to the present. The prognosis of HCDD is very poor, and optimal treatment has not been established. Only a few cases of HCDD with favorable long-term renal prognosis have been reported to date...
July 17, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28706010/clinical-management-of-potential-toxicities-and-drug-interactions-related-to-cyclin-dependent-kinase-4-6-inhibitors-in-breast-cancer-practical-considerations-and-recommendations
#7
REVIEW
Laura M Spring, Mark L Zangardi, Beverly Moy, Aditya Bardia
Aberrations of the cell cycle are pervasive in cancer, and selective cell cycle inhibition of cancer cells is a target of choice for a number of novel cancer therapeutics. Cyclin-dependent kinases (CDKs) are key regulatory enzymes that control cell cycle transitions and the commitment to cell division. Palbociclib and ribociclib are both orally active, highly selective reversible inhibitors of CDK4 and CDK6 that are approved by the U.S. Food and Drug Administration (FDA) for hormone receptor-positive metastatic breast cancer in combination with specific endocrine therapies...
July 13, 2017: Oncologist
https://www.readbyqxmd.com/read/28704757/structural-optimization-elaborates-novel-potent-akt-inhibitors-with-promising-anticancer-activity
#8
Yang Liu, Yanzhen Yin, Zhen Zhang, Carrie J Li, Hui Zhang, Daoguang Zhang, Changying Jiang, Krystle Nomie, Liang Zhang, Michael L Wang, Guisen Zhao
Targeting of Akt has been validated as a well rationalized approach to cancer treatment, and represents a promising therapeutic strategy for aggressive hematologic malignancies. We describe herein an exploration of novel Akt inhibitors for cancer therapy through structural optimization of previously described 4-(piperazin-1-yl)-7H-pyrrolo[2,3-d]pyrimidine derivatives. Our studies yielded a novel series of pyrrolopyrimidine based phenylpiperidine carboxamides capable of potent inhibition of Akt1. Notably, 10h exhibited robust antiproliferative effects in both mantle cell lymphoma cell lines and primary patient tumor cells...
June 30, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28696550/two-novel-variants-of-the-abcg5-gene-cause-xanthelasmas-and-macrothrombocytopenia-a-brief-review-of-hematological-abnormalities-of-sitosterolemia
#9
J M Bastida, R Benito, K Janusz, M Díez-Campelo, J M Hernández-Sánchez, S Marcellini, M Girós, J Rivera, M L Lozano, A Hortal, J M Hernández-Rivas, J R González-Porras
BACKGROUND: Sitosterolemia (STSL) is a recessive inherited disorder caused by pathogenic variants in ABCG5 and ABCG8 genes. Increased levels of plasma plant sterols (PS) usually produce xanthomas and premature coronary atherosclerosis, although hematological abnormalities may occasionally be present. This clinical picture is unfamiliar to many physicians, and patients may be at high risk of misdiagnosis. OBJECTIVES: To report two novel ABCG5 gene variants causing STSL in a Spanish patient, and review the clinical and mutational landscape of STSL...
July 11, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28696175/venetoclax-a-novel-b-cell-lymphoma-2-inhibitor-for-chronic-lymphocytic-leukemia-and-other-hematologic-malignancies
#10
Jacqueline L Olin, Carrie L Griffiths, Morgan B Smith
Patients with chronic lymphocytic leukemia with the 17p deletion have a poor prognosis and treatment options are limited. Venetoclax, a novel B-cell lymphoma-2 inhibitor, has been approved for treatment-experienced chronic lymphocytic leukemia patients with the 17p deletion. A phase 1 dose-escalation study to 400 mg daily showed overall response rates across all doses of 79% with a complete response achieved in 20%. A phase 2 multicenter open-label study demonstrated overall response rate of 79.4% of patients (95% confidence interval 70...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28694324/patient-reported-outcomes-in-hematology-is-it-time-to-focus-more-on-them-in-clinical-trials-and-hematology-practice
#11
Fabio Efficace, Gianluca Gaidano, Francesco Lo-Coco
In less than two decades, major clinical advances have been made in various areas of hematologic malignancies. Clinicians and patients now frequently face challenging choices regarding various treatments that are often similar in regard to safety or clinical effectiveness, hence medical decision-making has grown in complexity. For example, several novel drugs have been developed as oral agents introducing an additional challenge in patient management, such as ensuring an optimal adherence to therapy in order to maximize drug effectiveness...
July 10, 2017: Blood
https://www.readbyqxmd.com/read/28690315/targeting-nucleolin-for-better-survival-in-diffuse-large-b-cell-lymphoma
#12
N Jain, H Zhu, T Khashab, Q Ye, B George, R Mathur, R K Singh, Z Berkova, J F Wise, F K Braun, X Wang, K Patel, Z Y Xu-Monette, J Courty, K H Young, L Sehgal, F Samaniego
Anthracyclines have been a cornerstone in the cure of diffuse large B-cell lymphoma (DLBCL) and other hematological cancers. The ability of anthracyclines to eliminate DLBCL depends on the presence of topoisomerase-II-alpha (TopIIA), a DNA repair enzyme complex. We identified nucleolin as a novel binding partner of TopIIA. Abrogation of nucleolin sensitized DLBCL cells to TopIIA targeting agents (doxorubicin/etoposide). Silencing nucleolin and challenging DLBCL cells with doxorubicin enhanced the phosphorylation of H2AX (γH2AX-marker of DNA damage) and allowed DNA fragmentation...
July 10, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28684780/retinoic-acid-affects-lung-adenocarcinoma-growth-by-inducing-differentiation-via-gata6-activation-and-egfr-and-wnt-inhibition
#13
Giovanni Zito, Flores Naselli, Laura Saieva, Stefania Raimondo, Giovanna Calabrese, Claudio Guzzardo, Stefano Forte, Christian Rolfo, Rosalba Parenti, Riccardo Alessandro
A fundamental task in cancer research aims at the identification of new pharmacological therapies that can affect tumor growth. Differentiation therapy might exploit this function not only for hematological diseases, such as acute promyelocytic leukemia (APML) but also for epithelial tumors, including lung cancer. Here we show that Retinoic Acid (RA) arrests in vitro and in vivo the growth of Tyrosine Kinase Inhibitors (TKI) resistant Non Small Cell Lung Cancer (NSCLC). In particular, we found that RA induces G0/G1 cell cycle arrest in TKI resistant NSCLC cells and activates terminal differentiation programs by modulating the expression of GATA6, a key transcription factor involved in the physiological differentiation of the distal lung...
July 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28675065/hypomethylating-agents-hma-treatment-for-myelodysplastic-syndromes-alternatives-in-the-frontline-and-relapse-settings
#14
Natalie Uy, Abhay Singh, Steven D Gore, Thomas Prebet
Hypomethylating agents (HMA) have played a pivotal role for treating myelodysplastic syndromes (MDS) over the past decade, inducing sustained hematological responses and delaying progression to leukemia. However, a vast majority of patients will experience treatment failure within 2 years, with poor prognoses and limited options, and management of this growing patient population remains unclear. Areas Covered: With the introduction of new agents in the MDS field, a better understanding of the biology of MDS, and updated information on standard of care options (including allogeneic transplantation), we re-evaluate the global treatment strategy in MDS via novel agents, focusing in particular on investigational approaches for patients who fail to respond to HMA when applicable...
July 4, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28671573/histone-deacetylase-inhibitors-as-anticancer-drugs
#15
REVIEW
Tomas Eckschlager, Johana Plch, Marie Stiborova, Jan Hrabeta
Carcinogenesis cannot be explained only by genetic alterations, but also involves epigenetic processes. Modification of histones by acetylation plays a key role in epigenetic regulation of gene expression and is controlled by the balance between histone deacetylases (HDAC) and histone acetyltransferases (HAT). HDAC inhibitors induce cancer cell cycle arrest, differentiation and cell death, reduce angiogenesis and modulate immune response. Mechanisms of anticancer effects of HDAC inhibitors are not uniform; they may be different and depend on the cancer type, HDAC inhibitors, doses, etc...
July 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28670978/a-novel-blk-induced-tumor-model
#16
David Leander Petersen, Jens Berthelsen, Andreas Willerslev-Olsen, Simon Fredholm, Sally Dabelsteen, Charlotte Menné Bonefeld, Carsten Geisler, Anders Woetmann
B-lymphoid tyrosine kinase (BLK) is a non-receptor tyrosine kinase belonging to the SRC family kinases. BLK is known to be functionally involved in B-cell receptor signaling and B-cell development. New evidence suggests that B-lymphoid tyrosine kinase is ectopically expressed and is a putative oncogene in cutaneous T-cell lymphoma and other T-cell malignancies. However, little is known about the role of BLK in lymphomagenesis, and the oncogenic function seems to depend on the cellular context. Importantly, BLK is also ectopically expressed in other hematological and multiple non-hematological malignancies including breast, kidney, and lung cancers, suggesting that BLK could be a new potential target for therapy...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28668320/engineering-natural-killer-cells-for-cancer-immunotherapy
#17
REVIEW
Katayoun Rezvani, Rayne Rouce, Enli Liu, Elizabeth Shpall
The past several years have seen tremendous advances in the engineering of immune effector cells as therapy for cancer. While chimeric antigen receptors (CARs) have been used extensively to redirect the specificity of autologous T cells against hematological malignancies with striking clinical results, studies of CAR-modified natural killer (NK) cells have been largely preclinical. In this review, we focus on recent advances in NK cell engineering, particularly on preclinical evidence suggesting that NK cells may be as effective as T cells in recognizing and killing targets after genetic modification...
June 28, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28659921/patient-s-natural-killer-cells-in-the-era-of-targeted-therapies-role-for-tumor-killers
#18
Meriem Messaoudene, Alexandra Frazao, Pierre Jean Gavlovsky, Antoine Toubert, Nicolas Dulphy, Anne Caignard
Natural killer (NK) cells are potent antitumor effectors, involved in hematological malignancies and solid tumor immunosurveillance. They infiltrate various solid tumors, and their numbers are correlated with good outcome. The function of NK cells extends their lytic capacities toward tumor cells expressing stress-induced ligands, through secretion of immunoregulatory cytokines, and interactions with other immune cells. Altered NK cell function due to tumor immune escape is frequent in advanced tumors; however, strategies to release the function of NK infiltrating tumors are emerging...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28653974/hla-g-3-utr-polymorphisms-predict-drug-induced-g3-4-toxicity-related-to-folinic-acid-5-fluorouracil-oxaliplatin-folfox4-chemotherapy-in-non-metastatic-colorectal-cancer
#19
Marica Garziera, Saverio Virdone, Elena De Mattia, Lucia Scarabel, Erika Cecchin, Jerry Polesel, Mario D'Andrea, Nicoletta Pella, Angela Buonadonna, Adolfo Favaretto, Giuseppe Toffoli
Polymorphisms in drug-metabolizing enzymes might not completely explain inter-individual differences in toxicity profiles of patients with colorectal cancer (CRC) that receive folinic acid/5-fluorouracil/oxaliplatin (FOLFOX4). Recent data indicate that the immune system could contribute to FOLFOX4 outcomes. In light of the immune inhibitory nature of human leukocyte antigen-G (HLA-G), a non-classical major histocompatibility complex (MHC) class I molecule, we aimed to identify novel genomic markers of grades 3 and 4 (G3-4) toxicity related to FOLFOX4 therapy in patients with CRC...
June 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28653295/targeting-the-wnt-pathway-in-cancer-a-review-of-novel-therapeutics
#20
Roya Tabatabai, Yuliya Linhares, David Bolos, Monica Mita, Alain Mita
Wnt signaling is an evolutionarily conserved pathway that controls cell-to-cell interactions during embryogenesis. In adults, Wnt signaling plays a role in tissue homeostasis in almost every organ system. Aberrations within this pathway are implicated in a spectrum of human diseases. A variety of perturbations have been described in both solid and hematologic malignancies, lending way to Wnt signaling as a target for anti-cancer therapy. Of particular interest is the role of Wnt signaling in the development and maintenance of cancer stem cells, a rare population of cells that are able to maintain a tumor via self-renewal and thought to be more resistant to chemotherapy than bulk tumor cells...
June 26, 2017: Targeted Oncology
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