Jan 30th, 2023 - Myelofibrosis treatment with the Janus kinase (JAK) inhibitor momelotinib resulted in clinically significant improvements in symptoms and spleen response compared with danazol for symptomatic, JAK inhibitor-exposed patients with anemia and intermediate- or high-risk disease, the phase III MOMENTUM trial showed. A significantly greater proportion of patients in the momelotinib group reported a ≥...

Jan 30th, 2023 - Patients with systemic lupus erythematosus (SLE) showed reduced antibody responses following COVID-19 vaccination, with drugs for the condition such as belimumab (Benlysta) and mycophenolate mofetil (MMF) likely to blame, researchers said. Immunoglobulin G (IgG) titers measured 2 weeks after the second dose of mRNA COVID vaccines were lower by about 20% among 342 lupus patients compared with th...

Jan 29th, 2023 - Renal cell carcinoma (RCC) is not sensitive to immunotherapy and has poor prognosis. DNA methylation regulates gene expression, and its abnormal changes are related to many human diseases. Recently, DNA methylation has been found to participate in immune infiltration in various cancers. However, its pattern in RCC remains poorly understood. We found that IL18 was significantly over-expressed in...

Jan 29th, 2023 - FLT3 inhibitors (FLT3i) are drugs in which there is limited experience and not yet enough information on the mechanisms of absorption, transport, and elimination; but especially on the potential drug-drug interactions (DDIs). There are therefore risks in the management of FLT3i DDIs (i.e., sorafenib, ponatinib, crenolanib, midostaurin, quizartinib, and gilteritinib) and ignoring them can compro...

Jan 29th, 2023 - Autophagy is a complex process of lysosomal-dependent degradation of unwanted cellular material. In response to endogenous or exogenous stimuli, autophagy is induced and regulated by two kinases: the AMP activated kinase (AMPK) and the mammalian target of rapamycin (mTOR). Cells activated by Unc-51-like kinase 1 (ULK1) form a double membrane complex that sequesters the cargo (phagophore) and el...

Jan 28th, 2023 - Use of immune checkpoint inhibitors (ICIs) in solid organ transplant recipients (SOTRs) with advanced skin cancers presents a significant clinical management dilemma. SOTRs and other immunosuppressed patients have been routinely excluded from ICI clinical trials with good reason: immune checkpoints play an important role in self- and allograft-tolerance and risk of acute allograft rejection rep...

Jan 28th, 2023 - SQ109 is a tuberculosis drug candidate that has high potency against Mycobacterium tuberculosis and is thought to function at least in part by blocking cell wall biosynthesis by inhibiting the MmpL3 transporter. It also has activity against bacteria and protozoan parasites that lack MmpL3, where it can act as an uncoupler, targeting lipid membranes and Ca2+ homeostasis. Here, we synthesized 18 ...

Jan 28th, 2023 - Central giant cell granuloma of the jaw (CGCJ) can be locally aggressive and result in facial and dental deformity. A child with CGCJ was treated surgically and with denosumab with a response but life-threatening toxicity. Imatinib, a tyrosine kinase inhibitor, was prescribed based on clinical similarities between CGCJ and cherubism, for which Imatinib has been effective. Within 2 months, a com...

Jan 28th, 2023 - Programmed death-1 (PD-1), an inhibitory receptor expressed on activated T cells, may suppress antitumor immunity. This phase I study sought to determine the safety and tolerability of anti-PD-1 blockade in patients with treatment-refractory solid tumors and to preliminarily assess antitumor activity, pharmacodynamics, and immunologic correlates. Thirty-nine patients with advanced metastatic me...

Jan 28th, 2023 - While immune checkpoint inhibitors (ICI) have had success with various malignancies, their efficacy in brain cancer is still unclear. Retrospective and prospective studies using PD-1 inhibitors for recurrent glioblastoma (GBM) have not established survival benefit. This study evaluated if ICI may be effective for select patients with recurrent GBM. This was a single-center retrospective study o...

Jan 28th, 2023 - The current standard of care for chronic-phase chronic myeloid leukemia (CP-CML) is tyrosine kinase inhibitors (TKIs). Treatment recommendations are unclear for CP-CML failing ≥ 2 lines of treatment, partly due to the paucity of head-to-head trials evaluating TKIs. Thus, matching-adjusted indirect comparisons (MAICs) were conducted to compare asciminib with competing TKIs in third- or later lin...

Jan 28th, 2023 - Treatment of chronic myeloid leukemia has improved significantly with the introduction of tyrosine kinase inhibitors (TKIs), and treatment guidelines based on numerous clinical trials are available for chronic phase disease. However for CML in the blast phase (CML-BP), prognosis remains poor and treatment options are much more limited. The spectrum of treatment strategies for children and adole...

Jan 28th, 2023 - Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are commonly used in the treatment of advanced non-small cell lung cancer. However, patients will inevitably develop resistance to EGFR-TKIs in the long-term treatment process. In this paper, we report a case of small cell lung cancer transformation after EGFR-TKIs treatment in lung adenocarcinoma. We summarize the characte...

Jan 28th, 2023 - The high mobility group A1 (HMGA1) gene is overexpressed in malignant tumors, and its expression level correlates with the progression and metastasis of tumors. However, the specific role of HMGA1 in hepatocellular carcinoma (HCC) and relevant influencing approaches in tumor immunity remain unclear. In this study, the expression and clinical significance of HMGA1 in HCC immunity were analyzed. ...

Jan 28th, 2023 - Dysregulated APRIL/BAFF signaling is implicated in the pathogenesis of multiple autoimmune diseases, including SLE and LN. A high affinity APRIL/BAFF antagonist was developed to overcome the clinical limitations of existing B cell inhibitors. A variant of TACI-Fc generated by directed evolution showed enhanced binding for both APRIL and BAFF and was designated povetacicept (ALPN-303). Povetacic...

Jan 28th, 2023 - The incidence of myeloid neoplasms following treatment with poly (ADP-ribose) polymerase inhibitors (PARPi) in patients with ovarian cancer has been gradually increasing over the last few years. The cumulative exposure to PARPi and the improved overall survival of patients with ovarian cancer may represent key underlying explanations behind such trend. Fortunately, the earlier introduction of P...

Jan 28th, 2023 - The past 5 years have seen several fundamental advances in ovarian cancer, with important new insights towards novel therapeutic opportunities within the DNA repair pathway. With the incorporation of poly (ADP-ribose) polymerase inhibitors (PARPi) into maintenance treatment regimens, the management of short- and long-term adverse events are key clinical priorities. Currently, three different PA...

Jan 27th, 2023 - SAN FRANCISCO – Adding stereotactic body radiation therapy (SBRT) to sorafenib produced better outcomes among patients with hepatocellular carcinoma (HCC) than sorafenib alone, according to new findings. The use of SBRT in this setting improved both overall survival and progression-free survival (PFS).

Jan 27th, 2023 - Background: Hairy cell leukemia (HCL) is an indolent CD22+ B-cell leukemia comprising 2% of all leukemias, or approximately 1200 of the 62,130 new cases of leukemia/year in the US. HCL variant (HCLv), also CD22+, is 10-20% as common as HCL, but more common in the relapsed/refractory population due to its poor prognosis and response to standard purine analog chemotherapy. HCLv cells are CD25-neg...

Jan 27th, 2023 - PRIMARY OBJECTIVES: I. To determine a maximum tolerated dose or maximum administrated dose of anti-lymphocyte activation gene-3 (LAG-3) antibody (BMS-986016) (anti-LAG-3 monoclonal antibody BMS-986016) and anti-cluster of differentiation 137 (CD137) antibody (BMS- 663513) (urelumab) given independently and in combination with anti-programmed death-1 (PD-1) antibody (nivolumab, BMS-936558) safel...