Article
Biochemistry & Molecular Biology
Brigitte Bauvois, Elodie Pramil, Ludovic Jondreville, Claire Quiney, Florence Nguyen-Khac, Santos A. Susin
Summary: The study reveals that both type I and II interferons promote survival of chronic lymphocytic leukemia cells by activating the STAT3/Mcl-1 signaling pathway, inhibiting intrinsic apoptosis. Inhibitors against STAT3, TYK2 (for type I IFN), JAK2 (for type II IFN), and Src family kinase PP2 can effectively reduce interferon-mediated cell survival. Combining conventional treatments with inhibitors targeting STAT3 and Mcl-1 may offer a new therapeutic strategy for CLL.
Article
Biochemistry & Molecular Biology
Carmen Cervellera, Maria Russo, Serena Dotolo, Angelo Facchiano, Gian Luigi Russo
Summary: Based on the experimental structure of AKT-1, the compound STL1 and flavonoid quercetin were identified as allosteric inhibitors of AKT, targeting Ser473 phosphorylation and directly binding CK2 and PI3K kinases respectively to inhibit the PI3K/AKT pathway. The combined treatment of quercetin and STL1 exhibited synergistic effects in inhibiting cell growth and inducing apoptosis, leading to a switch from protective to non-protective autophagy in drug-resistant cells.
Review
Cell Biology
Matthew L. Winder, Kirsteen J. Campbell
Summary: MCL-1, a pro-survival member of the BCL-2 family, has emerged as an attractive target in breast cancer due to its potential to restore apoptosis and enhance the efficacy of conventional therapies.
Article
Oncology
Xue Yi, Nitin Jain, LaKesla R. Iles, Mary L. Ayres, William G. Wierda, Varsha Gandhi
Summary: The B-cell receptor signaling pathway and Bcl-2 family prosurvival proteins play important roles in chronic lymphocytic leukemia. Combined treatment with ibrutinib and venetoclax shows high rates of remission in CLL patients, but some patients do not achieve complete remission. This study suggests that cells persistent during ibrutinib and venetoclax therapy might be sensitive to the combined use of venetoclax and Mcl-1 inhibitor AMG-176.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Hyunsoo Cho, Ji Eun Jang, Ju-In Eom, Hoi-Kyung Jeung, Haerim Chung, Jin Seok Kim, June-Won Cheong, Yoo Hong Min
Summary: The study demonstrated the synergistic effects of venetoclax and arsenic trioxide on AML leukemia stem cells, suggesting a potential combination therapy for acute leukemia treatment. Venetoclax efficiently induced apoptosis and impaired cell viability when combined with ATO, showing promising antileukemic effects.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2021)
Article
Oncology
Shenmiao Yang, Abraham M. Varghese, Nitin Sood, Carlos Chiattone, Norah O. Akinola, Xiaojun Huang, Robert Peter Gale
Summary: East Asians, Asian Indians, and Amerindians have a significantly lower incidence rate of chronic lymphocytic leukemia compared to persons of European descent, suggesting a genetic rather than environmental basis for this disparity. These populations have different genetic admixtures with archaic hominins, potentially explaining the varying CLL incidences among them, as well as differences in clinical and molecular covariates of CLL. Further research is needed to determine the exact reasons behind these population variances in CLL and other lymphomas and cancers.
Article
Oncology
Shady I. Tantawy, Aloke Sarkar, Stefan Hubner, Zhi Tan, William G. Wierda, Abdelraouf Eldeib, Shuxing Zhang, Steven Kornblau, Varsha Gandhi
Summary: This study aims to investigate the mechanism of MCL-1i-induced Mcl-1 protein stability. Both in vivo and in vitro experiments demonstrate that MCL-1i-induced Mcl-1 protein stability is mainly associated with defective Mcl-1 ubiquitination and concurrent apoptosis induction. Additionally, MCL-1i also enhances Mcl-1Thr163 phosphorylation via ERK pathway, contributing to Mcl-1 stability.
CLINICAL CANCER RESEARCH
(2023)
Review
Medicine, General & Internal
Shenmiao Yang, Xiaojun Huang, Robert Peter Gale
Summary: Transplantation has been used to treat chronic lymphocytic leukemia for over 35 years, but is only considered for less than 1% of highly selected patients. While some patients may achieve long-term leukemia-free survival with transplants, they also come with significant morbidity and mortality. The anti-leukemia effects of transplants are influenced by various factors, including drugs, radiation, and immune mechanisms.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Medicine, General & Internal
Tanya Siddiqi, David G. Maloney, Saad S. Kenderian, Danielle M. Brander, Kathleen Dorritie, Jacob Soumerai, Peter A. Riedell, Nirav N. Shah, Rajneesh Nath, Bita Fakhri, Deborah M. Stephens, Shuo Ma, Tatyana Feldman, Scott R. Solomon, Stephen J. Schuster, Serena K. Perna, Sherilyn A. Tuazon, San -San Ou, Eniko Papp, Leanne Peiser, Yizhe Chen, William G. Wierda
Summary: In this study, lisocabtagene maraleucel (liso-cel) was evaluated for its efficacy and safety in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma. The results showed that liso-cel induced complete response or remission in patients, including those who had previously failed treatment with a BTK inhibitor and venetoclax. The safety profile was manageable.
Article
Genetics & Heredity
Qiuyi Zhang, Ying Gao, Shuchun Lin, Lynn R. Goldin, Yonghong Wang, Holly Stevenson, Daniel C. Edelman, Keith Killian, Gerald Marti, Paul S. Meltzer, Song Xiang, Neil E. Caporaso
Summary: This study investigated the DNA methylation aberrations in malignant B lymphocytes of CLL patients and identified differentially methylated positions (DMPs) and differentially methylated and expressed genes (DMEGs) associated with CLL by integrating public databases. The direction of each DMEG in CLL was observed based on DMPs in the promoter and the body region, and the methylation heterogeneity of CLL subgroups and the effect of B cell maturation on CLL were explored. The findings suggest the importance of DNA methylation in the pathogenesis of CLL and provide potential markers for diagnostic and therapeutic purposes.
FRONTIERS IN GENETICS
(2023)
Article
Oncology
Carmela Ciardullo, Katarzyna Szoltysek, Peixun Zhou, Monika Pietrowska, Lukasz Marczak, Elaine Willmore, Amir Enshaei, Anna Walaszczyk, Jia Yee Ho, Vikki Rand, Scott Marshall, Andrew G. Hall, Christine J. Harrison, Meera Soundararajan, Jeyanthy Eswaran
Summary: This study investigates the clinical significance of B-cell regulators BACH2 and BCL6 in chronic lymphocytic leukaemia (CLL). The results show that low levels of BACH2 and BCL6 RNA expression are associated with shorter overall survival in CLL patients.
Article
Oncology
Stefania Fiorcari, Rossana Maffei, Claudio Giacinto Atene, Nicolo Mesini, Monica Maccaferri, Giovanna Leonardi, Silvia Martinelli, Ambra Paolini, Vincenzo Nasillo, Giulia Debbia, Leonardo Potenza, Mario Luppi, Roberto Marasca
Summary: Chronic lymphocytic leukemia (CLL) has undergone a clinical revolution due to the discovery of key pathogenic mechanisms, but remains an incurable disease due to intrinsic or acquired resistance of the leukemic clone. High levels of Notch2 and Mcl-1 may contribute to increased resistance to venetoclax in CLL cells, and reducing Mcl-1 expression or silencing Notch2 can restore the response to venetoclax.
FRONTIERS IN ONCOLOGY
(2022)
Article
Cell Biology
Flore Sneyers, Martijn Kerkhofs, Femke Speelman-Rooms, Kirsten Welkenhuyzen, Rita La Rovere, Ahmed Shemy, Arnout Voet, Guy Eelen, Mieke Dewerchin, Stephen W. G. Tait, Bart Ghesquiere, Martin D. Bootman, Geert Bultynck
Summary: Intracellular Ca2+ signals play a crucial role in various cellular processes. Research has shown that BAPTAi can induce apoptosis in cancer cells by inhibiting mTORC1 activity and impairing glycolysis, independent of Ca2+ signaling. Additionally, direct inhibition of PFKFB3 emerges as a potential therapeutic target in MCL-1-dependent cancers.
CELL DEATH & DISEASE
(2023)
Article
Oncology
Ana Vagos Mata, Eduardo Espada, Daniela Alves, Blanca Polo, Maria Joao Costa, Conceicao Lopes, Joao F. Lacerda, Joao Raposo
Summary: R-HDMP is a valuable treatment option for elderly and frail patients with CLL/SLL, with low risk of severe myelotoxicity and other severe adverse events. It has been shown to serve as a bridge to other lines of treatment, including chemo-immunotherapy.
Article
Medicine, General & Internal
Amarpreet Devi, Lieze Thielemans, Eleni E. Ladikou, Taran K. Nandra, Timothy Chevassut
Summary: Lymphocytosis is a common blood-test finding that requires clinical evaluation to determine whether it is benign or malignant. Most chronic lymphocytic leukemia (CLL) patients are identified incidentally through routine blood tests. Patient outcomes are influenced by genetic predisposition and various prognostic markers. Chemo-immunotherapy is an effective treatment strategy for the majority of patients, and novel oral therapies are being developed.
Article
Biochemistry & Molecular Biology
Maria Russo, Carmela Spagnuolo, Stefania Moccia, Idolo Tedesco, Fabio Lauria, Gian Luigi Russo
Summary: Cancer is a major cause of death worldwide. Resistance to chemo- and radiotherapy is a common hurdle in cancer treatment. This study investigated the role of cellular senescence in radiotherapy resistance and demonstrated that senolytic agents can enhance the effectiveness of radiotherapy in killing cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Chemistry, Medicinal
Anil Pawar, Maria Russo, Isha Rani, Kalyan Goswami, Gian Luigi Russo, Amit Pal
Summary: The interim results of large trials on COVID-19 using antiviral drugs show little to no effect, leading to a continued search for alternate drugs and supplements. This review highlights the possible efficacy of quercetin in treating and preventing severe acute respiratory syndrome coronavirus and its comorbidities. Multiple clinical trials are currently assessing the efficacy of quercetin and other drugs/supplements for COVID-19. Despite its therapeutic properties, further trials are needed to establish its clinical efficacy.
PHYTOTHERAPY RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Giuseppina Crescente, Giuseppe Minervini, Carmela Spagnuolo, Stefania Moccia
Summary: To alleviate orofacial pain and improve patients' quality of life, researchers and healthcare professionals are seeking new alternatives, including the use of bioactive compounds from Cannabis sativa L. These compounds, such as non-psychoactive cannabinoids, flavonoids, and terpenes, show promising effects in reducing pain intensity by acting on multiple mechanisms, including inflammation and the endocannabinoid system.
Article
Nutrition & Dietetics
Carmela Spagnuolo, Stefania Moccia, Idolo Tedesco, Giuseppina Crescente, Maria Grazia Volpe, Maria Russo, Gian Luigi Russo
Summary: Regular consumption of olive oil is associated with protection against chronic-degenerative diseases, such as cancer. Epidemiological evidence indicates an inverse association between olive oil intake and bladder cancer risk. We investigated the anti-proliferative effects of a phenolic extract prepared from an extra virgin olive oil (EVOOE) on two human bladder cancer cell lines, and the results suggest that the mixture of phenolic compounds in extra virgin olive oil activates different anti-proliferative pathways.
Article
Oncology
Maria Russo, Stefania Moccia, Diomira Luongo, Gian Luigi Russo
Summary: The role of autophagy and senescence in cancer resistance to ionizing radiation is still not fully understood. This study found that the flavonoids quercetin and fisetin can induce autophagy and senescence-associated inflammatory markers by activating AMPK and inhibiting the ERK pathway. The combined treatment promotes autophagy and senescence induction, lowers the threshold for cell death, and induces apoptosis.
Article
Biochemistry & Molecular Biology
Carmela Spagnuolo, Federica Moccia, Idolo Tedesco, Eva Adabbo, Lucia Panzella, Gian Luigi Russo, Alessandra Napolitano
Summary: The extract obtained from the waste of fermented strawberry distillate production exhibited high antioxidant and antiproliferative properties, mainly attributed to the presence of ellagic acid and p-coumaric acid. It showed strong antiproliferative effects on human cancer cell lines, especially on HL-60 cells, through rapid apoptosis induction. The extract also exhibited antioxidant activity and modulation of cellular oxidative stress and signaling pathways.
Article
Food Science & Technology
Deborah Giordano, Angelo Facchiano, Stefania Moccia, Anna Maria Iole Meola, Gian Luigi Russo, Carmela Spagnuolo
Summary: The aryl hydrocarbon receptor (AhR) is an important environmental sensor involved in various cellular processes and plays a key role in conditions such as cancer, inflammation, and aging. This study aims to investigate the inhibitory activity of selected natural compounds on AhR. Through computational modeling and docking simulations, additional binding pockets related to AhR inhibition were discovered. In vitro experiments confirmed the efficacy of beta-carotene and ellagic acid in inhibiting AhR activation, validating the computational approach.
Article
Pharmacology & Pharmacy
Claudia Cerella, Mario Dicato, Marc Diederich
Summary: Immune checkpoint inhibitors are a promising class of immunotherapeutic agents for cancer treatment. However, many patients develop resistance to these drugs, and there is a lack of predictive markers for treatment response. Recent research has identified immune cell composition, T-cell status, and spatial distribution within the tumor microenvironment as important factors for prognosis and therapeutic response.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Food Science & Technology
Giuseppina Crescente, Giovanni Cascone, Antonio Petruzziello, Aziz Bouymajane, Maria Grazia Volpe, Gian Luigi Russo, Stefania Moccia
Summary: The wine industry generates a significant amount of grape pomace, which is a waste product that needs proper disposal. Two different technologies, microwave hydrodiffusion and gravity (MHG) and ultrasound-assisted extraction (UAE), were used to extract valuable bioactive compounds from grape pomace. The extracts were further purified through solid-phase extraction (SPE) to obtain three fractions, F1, F2, and F3. It was found that F2-MHG and F3-MHG had phenol contents 6.5 and 8.5 times higher than the non-fractionated extracts, respectively.