50,091 results match your criteria inhibitor efficacy

Therapeutic review of cabotegravir/rilpivirine long-acting antiretroviral injectable and implementation considerations at an HIV specialty clinic.

Pharmacotherapy 2021 Jun 15. Epub 2021 Jun 15.

Indiana University Health, Indianapolis, Indiana, USA.

Cabotegravir/rilpivirine (CAB/RPV) was recently approved by the US Food and Drug Administration (FDA) as the first complete parenteral antiretroviral (ART) regimen for treatment of people living with HIV (PLWH). As a monthly intramuscular (IM) injection, this therapy constitutes a major departure from the traditional paradigm of oral therapy requiring (at least) daily administration that has defined HIV treatment for decades. Composed of a second-generation integrase inhibitor (INSTI) and nonnucleoside reverse transcriptase inhibitor (NNRTI), CAB/RPV has achieved high rates of sustained virologic suppression with a favorable safety profile for treatment-experienced PLWH following oral lead-in (OLI) during several clinical trials. Read More

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Clinical Efficacy of Ponatinib in Philadelphia-Positive T-Cell Acute Lymphoblastic Leukemia with Extramedullary Involvement.

Acta Haematol 2021 Jun 15:1-5. Epub 2021 Jun 15.

Istituto di Ematologia "Seràgnoli" IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

T-cell acute lymphoblastic leukemia (T-ALL) is a rare entity in the adult acute leukemia setting. Translocation (9;22)(q34;q11) and BCR-ABL1 rearrangement are occasionally found in T-ALL and have been reported in no more than 100 cases in the literature (most of which are chronic myeloid leukemia blast crisis). Here, we report the remarkable effectiveness of third-generation tyrosine-kinase inhibitor ponatinib in obtaining hematological and metabolic remission, in a patient with Philadelphia chromosome-positive de novo T-ALL and outcomes of a therapeutic strategy containing chemotherapy intensification, nelarabine, and allogeneic hematopoietic stem cell transplantation. Read More

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Preclinical evidence of synergism between atovaquone and chemotherapy by AMPK-dependent mitochondrial dysfunction.

Eur J Pharmacol 2021 Jun 12:174256. Epub 2021 Jun 12.

Department of Pulmonary and Critical Care Medicine, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, China. Electronic address:

Chemoresistance has been associated with increased reliance on mitochondrial functions in many cancers, including lung cancer. Atovaquone is an anti-malaria drug and mitochondrial inhibitor. In this work, we attempted to explore whether atovaquone can be repurposed for lung cancer treatment to overcome chemoresistance. Read More

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Retrospective study of treatment patterns and outcomes post-lenalidomide for multiple myeloma in Canada.

Eur J Haematol 2021 Jun 15. Epub 2021 Jun 15.

Cross Cancer Institute, University of Alberta, Canada.

Lenalidomide is an important component of initial therapy in newly-diagnosed multiple myeloma, either as maintenance therapy post-autologous stem cell transplantation (ASCT) or as first-line therapy with dexamethasone for patients' ineligible for ASCT (non-ASCT). This retrospective study investigated treatment patterns and outcomes for ASCT-eligible and -ineligible patients who relapsed after lenalidomide as part of first-line therapy, based on data from the Canadian Myeloma Research Group Database for patients treated between January 2007 and April 2019. Among 256 patients who progressed on lenalidomide maintenance therapy, 28. Read More

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The association between neurohormonal therapy and mortality in older adults with heart failure with reduced ejection fraction.

J Am Geriatr Soc 2021 Jun 15. Epub 2021 Jun 15.

The Dartmouth Institute, Geisel School of Medicine, Hanover, New Hampshire, USA.

Background/objectives: Neurohormonal therapy, which includes beta-blockers and angiotensin-converting enzyme inhibitor/angiotensin receptor blockers (ACEi/ARBs), is the cornerstone of heart failure with reduced ejection fraction (HFrEF) treatment. While neurohormonal therapies have demonstrated efficacy in randomized clinical trials, older patients, which now comprise the majority of HFrEF patients, were underrepresented in those original trials. This study aimed to determine the association between short- (30 day) and long-term (1 year) mortality and the use of neurohormonal therapy in HFrEF patients, across the age spectrum. Read More

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Probenecid increases renal retention and antitumor activity of DFMO in neuroblastoma.

Cancer Chemother Pharmacol 2021 Jun 15. Epub 2021 Jun 15.

Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, 400 Monroe Ave, NW, Grand Rapids, MI, 49503, USA.

Background: Neuroblastoma (NB) is the most common extracranial solid tumor in children. Interference with the polyamine biosynthesis pathway by inhibition of MYCN-activated ornithine decarboxylase (ODC) is a validated approach. The ODC inhibitor α-difluoromethylornithine (DFMO, or Eflornithine) has been FDA-approved for the treatment of trypanosomiasis and hirsutism and has advanced to clinical cancer trials including NB as well as cancer-unrelated human diseases. Read More

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Evaluation of Long-Lasting Potential of Suprachoroidal Axitinib Suspension Via Ocular and Systemic Disposition in Rabbits.

Transl Vis Sci Technol 2021 Jun;10(7):19

Clearside Biomedical Inc., Alpharetta, GA, USA.

Purpose: Axitinib, a tyrosine kinase inhibitor, is a potent inhibitor of vascular endothelial growth factor (VEGF) receptors -1, -2 and -3. Suprachoroidal (SC) delivery of axitinib, combined with pan-VEGF inhibition activity of axitinib, has the potential to provide additional benefits compared to the current standard of care with intravitreal anti-VEGF-A agents. This study evaluated the ocular pharmacokinetics and systemic disposition of axitinib after SC administration in rabbits. Read More

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Precise medicine of programmed cell death-1/programmed cell death 1 ligand 1 inhibitor immunotherapy combined radiotherapy for inoperable advanced lung cancer: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Jun;100(24):e26367

Pneumology Department, 986 Hospital of People's Liberation Army Air Force, Xi'an, Shaan Xi, P.R. China.

Background: Programmed cell death-1/programmed cell death 1 ligand 1 (PD-1/PD-L1) inhibitors are a group of immune checkpoint inhibitors immunotherapy for cancer treatment. These immune checkpoint inhibitors are becoming first-line treatments for several types of cancer. Radiotherapy for cancer is a traditional treatment and the therapeutic effect is not satisfactory due to the side effect of chemotherapeutic drugs. Read More

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Androgen receptor signalling inhibitors: post-chemotherapy, pre-chemotherapy and now in castration sensitive prostate cancer.

Endocr Relat Cancer 2021 Jun 1. Epub 2021 Jun 1.

S Kaochar, Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States.

Based on pioneering work by Huggins, Hodges and others, hormonal therapies have been established as an effective approach for advanced prostate cancer (PC) for the past 8 decades. However, it quickly became evident that androgen deprivation therapy (ADT) via surgical or medical castration accomplishes inadequate inhibition of the androgen receptor (AR) axis, with clinical resistance inevitably emerging due to adrenal and intratumoral sources of androgens and other mechanisms. Early efforts to augment ADT by adding adrenal-targeting agents (aminoglutethimide, ketoconazole) or AR antagonists (flutamide, bicalutamide, nilutamide, cyproterone) failed to achieve overall survival (OS) benefits, although they did exhibit some evidence of limited clinical activity. Read More

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Combined treatment with FABP4 inhibitor ameliorates rosiglitazone-induced liver steatosis in obese diabetic db/db mice.

Basic Clin Pharmacol Toxicol 2021 Jun 15. Epub 2021 Jun 15.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.

Rosiglitazone has been reported to exert dual effects on liver steatosis, and it could exacerbate liver steatosis in obese animal models, which was suggested to be closely related to the elevated hepatic expression of FABP4. This study aimed to investigate whether combined treatment with FABP4 inhibitor I-9 could alleviate rosiglitazone-induced liver steatosis in obese diabetic db/db mice. Male C57BL/KsJ-db/db mice were orally treated with rosiglitazone, rosiglitazone combined with I-9 daily for 8 weeks. Read More

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IGF1 receptor inhibition amplifies the effects of cancer drugs by autophagy and immune-dependent mechanisms.

J Immunother Cancer 2021 Jun;9(6)

Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, France

Background: Pharmacological autophagy enhancement constitutes a preclinically validated strategy for preventing or treating most major age-associated diseases. Driven by this consideration, we performed a high-content/high-throughput screen on 65 000 distinct compounds on a robotized fluorescence microscopy platform to identify novel autophagy inducers.

Results: Here, we report the discovery of picropodophyllin (PPP) as a potent inducer of autophagic flux that acts on-target, as an inhibitor of the tyrosine kinase activity of the insulin-like growth factor-1 receptor (IGF1R). Read More

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Berotralstat (BCX7353) is a novel oral prophylactic treatment for hereditary angioedema: Review of phase II and III studies.

Allergy Asthma Proc 2021 Jun 14. Epub 2021 Jun 14.

Background: Hereditary angioedema (HAE) is a rare genetic disorder characterized by unpredictable and potentially life-threatening episodes of swelling in various parts of the body. These attacks can be painful and debilitating, and affect apatient's quality of life. Every patient who experiences an attack should be treated with on-demand medication to mitigateattack severity and duration. Read More

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Long-Term Efficacy and Safety of Deutetrabenazine for Chorea in Huntington's Disease: Results From the ARC-HD Open-label Study.

CNS Spectr 2021 Apr;26(2):164-165

Teva Pharmaceutical Industries Ltd., Basel, Switzerland.

Background: Chorea is a prominent motor dysfunction in Huntington's disease (HD). Deutetrabenazine, a vesicular monoamine transporter 2 (VMAT2) inhibitor, is FDA-approved for the treatment of chorea in HD. In the pivotal, 12-week First-HD trial, deutetrabenazine treatment reduced the Unified Huntington's Disease Rating Scale (UHDRS) total maximal chorea (TMC) score versus placebo. Read More

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[The relationship between genotype of familial hypercholesterolemia and the efficacy of PCSK9 inhibitors].

Zhonghua Xin Xue Guan Bing Za Zhi 2021 Jun;49(6):572-579

Department of Arteriosclerosis, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China.

This study intends to explore the difference in the efficacy of PCSK9 inhibitors in patients with different FH phenotypes by analyzing the level of blood lipids before and after treatment with PCSK9 inhibitors in patients with familial hypercholesterolemia (FH) with different allele grades. Patients with FH phenotype, who admitted to Beijing Anzhen Hospital from January 2019 to October 2020, were enrolled. Age, sex and other clinical information were collected from enrolled, and the pathogenic genes were detected by the second generation sequencing technique. Read More

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Optimization and SAR research at the piperazine and phenyl rings of JNJ4796 as new anti-influenza A virus agents, part 1.

Eur J Med Chem 2021 Jun 5;222:113591. Epub 2021 Jun 5.

CAMS Key Laboratory of Antiviral Drug Research, Beijing Key Laboratory of Antimicrobial Agents, NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. Electronic address:

JNJ4796, a small molecule fuse inhibitor targeting the conserved stem region of hemagglutinin, effectively neutralized a broad spectrum of group 1 influenza A virus (IAV), and protected mice against lethal and sublethal influenza challenge after oral administration. In this study, we reported the modification and structure-activity relationship (SAR) of C (piperazine ring) and E (phenyl ring) rings of JNJ4796. Compound (R)-2c was identified to show excellent in vitro activity against IAV H1N1 and Oseltamivir-resistant IAV H1N1 stains (IC: 0. Read More

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mTORC2 regulates ribonucleotide reductase to promote DNA replication and gemcitabine resistance in non-small cell lung cancer.

Neoplasia 2021 Jun 11;23(7):643-652. Epub 2021 Jun 11.

Department of Medical Biochemistry and Molecular Biology, School of Medicine, MOE Key Laboratory of Tumor Molecular Biology, Jinan University, Guangzhou, China. Electronic address:

Ribonucleotide reductase (RNR) is the key enzyme that catalyzes the production of deoxyribonucleotides (dNTPs) for DNA replication and it is also essential for cancer cell proliferation. As the RNR inhibitor, Gemcitabine is widely used in cancer therapies, however, resistance limits its therapeutic efficacy and curative potential. Here, we identified that mTORC2 is a main driver of gemcitabine resistance in non-small cell lung cancers (NSCLC). Read More

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p38 inhibition enhances TCR-T cell function and antagonizes the immunosuppressive activity of TGF-β.

Int Immunopharmacol 2021 Jun 11;98:107848. Epub 2021 Jun 11.

Department of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, Chongqing Medical University, Chongqing 400016, China. Electronic address:

The efficacy of adoptive cell therapy (ACT) relies on the abilities of T cells in self-expansion, survival and the secretion of effector molecules. Here, we presented an optimized method to generate T cells with improved functions by supplementing the culture medium with p38 inhibitor and the combination of IL-7 and IL-15 or IL-2 alone. The addition of p38 inhibitor, Doramapimod or SB202190, to IL-7 and IL-15 culture largely increased the capacity of T cells in the proliferation with enrichment of the naïve-like subsets and expression of CD62L. Read More

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Solid-phase synthesis of curcumin mimics and their anticancer activity against human pancreatic, prostate, and colorectal cancer cell lines.

Bioorg Med Chem 2021 Jun 5;42:116249. Epub 2021 Jun 5.

Department of Chemical Sciences, University of Napoli Federico II, Via Cintia 4, 80126 Napoli, Italy. Electronic address:

Curcumin is a bioactive natural compound with a wide range of pharmacological properties, including antitumor activity; however, its clinical application has been limited because of its low solubility, stability, and bioavailability. In this study, a solid phase approach was proposed for the combinatorial synthesis of a mini library of the mimics of curcumin in good purity and yield. The non-effective findings in pancreatic cancer cells switched to strong growth inhibition and cell death efficacy for PC3 prostate cancer cells, and mimic 9, in which tyrosol (TYR) and homovanillyl alcohol (HVA) units were linked by a phosphodiester bond, was quite effective not only in cell growth inhibition but also in causing strong cell death under the study conditions and treatments that were not effective in PANC1 cells. Read More

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Remdesivir inhibits the polymerases of the novel filoviruses lloviu and Bombali virus.

Antiviral Res 2021 Jun 11:105120. Epub 2021 Jun 11.

Institute for Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Germany. Electronic address:

In recent years, a number of novel filoviruses (e.g. Lloviu virus (LLOV) and Bombali virus (BOMV)) have been discovered. Read More

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A new biological triangle in cancer: intestinal microbiota, immune checkpoint inhibitors and antibiotics.

Clin Transl Oncol 2021 Jun 14. Epub 2021 Jun 14.

Department of General Surgery, Institute of General Surgery, Clinical Medical College, Northern Jiangsu Province Hospital, Yangzhou University, Yangzhou, 225001, China.

Cancer immunotherapy has revolutionized the treatment of many malignant tumors. Although immune checkpoint inhibitors (ICIs) can reactivate the anti-tumor activity of immune cells, sensitivity to immune checkpoint inhibitor therapy depends on the complex tumor immune processes. In recent years, numerous researches have demonstrated the role of intestinal microbiota in immunity and metabolism of the tumor microenvironment, as well as the efficacy of immunotherapy. Read More

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Prognostic impact of resistance to bortezomib and/or lenalidomide in carfilzomib-based therapies for relapsed/refractory multiple myeloma: The Kyoto Clinical Hematology Study Group, multicenter, pilot, prospective, observational study in Asian patients.

Cancer Rep (Hoboken) 2021 Jun 14:e1476. Epub 2021 Jun 14.

Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Background: Combinatory strategies with carfilzomib (CFZ), a second-generation proteasome inhibitor, plus dexamethasone (DEX) with or without lenalidomide (LEN) have shown promising efficacy for patients with relapsed/refractory multiple myeloma (RRMM) in pivotal clinical trials. However, their effects on patients who were resistance to bortezomib (BTZ) and/or LEN have not been fully evaluated in a daily practice setting.

Aims: To evaluate the real-world efficacy and safety of CFZ-based treatments; that is, CFZ with LEN plus DEX (KRD therapy) and CFZ with DEX (KD therapy), in Asian patients, we conducted a multicenter pilot prospective observational study in the Kyoto Clinical Hematology Study Group. Read More

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Effective cholesterol lowering after myocardial infarction in patients with nephrotic syndrome may require a multi-pharmacological approach: a case report.

Eur Heart J Case Rep 2021 May 13;5(5):ytab151. Epub 2021 May 13.

Department of Endocrinology, Karolinska University Hospital Huddinge, Stockholm 141 86, Sweden.

Background: Nephrotic syndrome causes severe hypercholesterolaemia due to increased production and altered clearance of lipoproteins from the liver. It is challenging for patients with nephrotic syndrome and coronary heart disease to meet LDL-cholesterol (LDL-C) goals for secondary prevention with conventional lipid-lowering therapy.

Case Summary: We present a man with nephrotic syndrome caused by focal segmental glomerular sclerosis (FSGS) and hypercholesterolaemia. Read More

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Outcomes in Juvenile-Onset Spondyloarthritis.

Front Med (Lausanne) 2021 28;8:680916. Epub 2021 May 28.

Departamento de Reumatologia, Hospital General de Mexico, Mexico City, Mexico.

Some studies have suggested children with juvenile onset spondyloarthritis (JoSpA) have a relatively poor outcome compared to other juvenile idiopathic arthritis (JIA) categories, in regards to functional status and failure to attain remission. Thus, in the interest of earlier recognition and risk stratification, awareness of the unique characteristics of this group is critical. Herein, we review the clinical burden of disease, prognostic indicators and outcomes in JoSpA. Read More

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TP53 Mutational Status-Based Genomic Signature for Prognosis and Predicting Therapeutic Response in Pancreatic Cancer.

Front Cell Dev Biol 2021 26;9:665265. Epub 2021 May 26.

Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

TP53 mutation is a critical driver mutation that affects the carcinogenesis and prognosis of patients with pancreatic cancer (PC). Currently, there is no driver mutation-derived signature based on TP53 mutational status for prognosis and predicting therapeutic response in PC. In the present study, we characterized the TP53 mutational phenotypes in multiple patient cohorts and developed a prognostic TP53-associated signature based on differentially expressed genes between PC samples with mutated TP53 and wild-type TP53. Read More

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Targeting Pyrimidine Metabolism in the Era of Precision Cancer Medicine.

Front Oncol 2021 28;11:684961. Epub 2021 May 28.

State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China.

Metabolic rewiring is considered as a primary feature of cancer. Malignant cells reprogram metabolism pathway in response to various intrinsic and extrinsic drawback to fuel cell survival and growth. Among the complex metabolic pathways, pyrimidine biosynthesis is conserved in all living organism and is necessary to maintain cellular fundamental function (i. Read More

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Safety and Efficacy of Personalized Cancer Vaccines in Combination With Immune Checkpoint Inhibitors in Cancer Treatment.

Front Oncol 2021 28;11:663264. Epub 2021 May 28.

Department of Biotherapy, Cancer Center, West China Hospital of Sichuan University, Chengdu, China.

Cancer immunotherapy can induce sustained responses in patients with cancers in a broad range of tissues, however, these treatments require the optimized combined therapeutic strategies. Despite immune checkpoint inhibitors (ICIs) have lasting clinical benefit, researchers are trying to combine them with other treatment modalities, and among them the combination with personalized cancer vaccines is attractive. Neoantigens, arising from mutations in cancer cells, can elicit strong immune response without central tolerance and out-target effects, which is a truly personalized method. Read More

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The Efficacy and Safety of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Combined With Thymosin in Advanced Non-Small Cell Lung Cancer Patients Harboring Active Epidermal Growth Factor Receptor Mutations.

Front Oncol 2021 28;11:659065. Epub 2021 May 28.

Cancer Institute, Xinqiao Hospital, Army Medical University, Chongqing, China.

Objective: To explore the efficacy and safety of EGFR-TKI combined with thymosin therapy in advanced non-small cell lung cancer (NSCLC) patients harboring active EGFR mutations.

Methods: Patients confirmed as advanced NSCLC with active EGFR mutations were recruited from August 2008 to July 2018 retrospectively. Patients treated with EGFR-TKI were classified as the EGFR-TKI group. Read More

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Combination Strategies to Augment Immune Check Point Inhibitors Efficacy - Implications for Translational Research.

Front Oncol 2021 28;11:559161. Epub 2021 May 28.

Department of Medical Oncology, HealthCare Global Enterprises Limited, Bangalore, India.

Immune checkpoint inhibitor therapy has revolutionized the field of cancer immunotherapy. Even though it has shown a durable response in some solid tumors, several patients do not respond to these agents, irrespective of predictive biomarker (PD-L1, MSI, TMB) status. Multiple preclinical, as well as early-phase clinical studies are ongoing for combining immune checkpoint inhibitors with anti-cancer and/or non-anti-cancer drugs for beneficial therapeutic interactions. Read More

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Reprogramming the immunosuppressive microenvironment of IDH1 wild-type glioblastoma by blocking Wnt signaling between microglia and cancer cells.

Oncoimmunology 2021 Jun 6;10(1):1932061. Epub 2021 Jun 6.

Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, China.

The vast majority (>90%) of glioblastoma (GBM) patients belong to the isocitrate dehydrogenase 1 wild type (IDH1) group which exhibits a poor prognosis with a median survival of less than 15 months. This study demonstrated numerous immunosuppressive genes as well as β-catenin gene, pivotal for Wnt/β-catenin signaling, were upregulated in 206 IDH1 glioma patients using the Chinese Glioma Genome Atlas (CGGA) database. The increase in microglia with an immunosuppressive phenotype and the overexpression of β-catenin protein were further verified in IDH1 GBM patients and IDH1 GL261 glioma allografts. Read More

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Enteral lorlatinib after alectinib as a treatment option in anaplastic lymphoma kinase-positive non-small cell lung cancer with triple problems: carcinomatous meningitis, poor performance status, and dysphagia-a case report.

Respirol Case Rep 2021 Jul 3;9(7):e00796. Epub 2021 Jun 3.

Department of Medical Oncology Hirosaki University Graduate School of Medicine Aomori Japan.

Alectinib treatment is effective in patients with anaplastic lymphoma kinase gene rearrangement-positive non-small cell lung cancer (NSCLC; hereafter positive NSCLC) who exhibit central nervous system (CNS) relapse and poor performance status (PS). Lorlatinib treatment is effective upon failure of other ALK inhibitor-based treatments. However, much remains unknown about the efficacy of lorlatinib in patients with positive NSCLC, who have triple problems, carcinomatous meningitis, poor PS, and dysphagia, after alectinib treatment. Read More

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