keyword
https://read.qxmd.com/read/38701712/perspectives-and-challenges-in-developing-small-molecules-targeting-purine-nucleoside-phosphorylase
#1
REVIEW
Yangyang Chen, Yang Li, Jing Gao, Quanwei Yu, Yiwen Zhang, Jifa Zhang
As a cytosolic enzyme involved in the purine salvage pathway metabolism, purine nucleoside phosphorylase (PNP) plays an important role in a variety of cellular functions but also in immune system, including cell growth, apoptosis and cancer development and progression. Based on its T-cell targeting profile, PNP is a potential target for the treatment of some malignant T-cell proliferative cancers including lymphoma and leukemia, and some specific immunological diseases. Numerous small-molecule PNP inhibitors have been developed so far...
April 20, 2024: European Journal of Medicinal Chemistry
https://read.qxmd.com/read/38695144/outcomes-and-genetic-dynamics-of-acute-myeloid-leukemia-at-first-relapse
#2
JOURNAL ARTICLE
Alex Bataller, Hagop Kantarjian, Alexandre Bazinet, Tapan Kadia, Naval Daver, Courtney D DiNardo, Gautam Borthakur, Sanam Loghavi, Keyur Patel, Guilin Tang, Koji Sasaki, Nicholas J Short, Musa Yilmaz, Ghayas C Issa, Yesid Alvarado, Guillermo Montalban-Bravo, Abhishek Maiti, Hussein A Abbas, Koichi Takahashi, Sherry Pierce, Elias Jabbour, Guillermo Garcia-Manero, Farhad Ravandi
Patients with relapsed acute myeloid leukemia (rAML) experience dismal outcomes. We performed a comprehensive analysis of patients with rAML to determine the genetic dynamics and survival predictive factors. We analyzed 875 patients with newly diagnosed AML who received intensive treatment (IT) or low-intensity treatment (LIT). Of these patients, 197 experienced subsequent rAML. Data was available for 164 patients, with a median time from CR/CRi to relapse of 6.5 months. Thirty-five of the 164 patients (21%) experienced relapse after allogeneic hematopoietic stem cell transplantation (alloSCT)...
May 2, 2024: Haematologica
https://read.qxmd.com/read/38692356/complex-treatment-of-residual-metastatic-germ-cell-cancer-a-single-center-experience
#3
JOURNAL ARTICLE
Fruzsina Eszter Fazekas, Zsuzsanna Ujfaludi, Krisztina Biró, Zoltán Gábor Páhi, István Buzogány, Farkas Sükösd, Tibor Pankotai, Tamás Beöthe
BACKGROUND: Testicular cancer is the most common solid malignancy among men aged 15-35. Radical orchiectomy and platinum-based chemotherapy (BEP) are curative in the majority of patients, including advanced, metastatic cases. According to current urooncology guidelines all non-seminoma patients harbouring post-chemotherapy residual masses of ≥ 1cm should undergo salvage retroperitoneal lymph node dissection (RPLND). However, only 10% of residual tumors contain viable disease...
April 29, 2024: Journal of Biotechnology
https://read.qxmd.com/read/38691889/discovery-of-potent-and-novel-dual-nampt-brd4-inhibitors-for-efficient-treatment-of-hepatocellular-carcinoma
#4
JOURNAL ARTICLE
Chunjia Yin, Shuting Jia, Xiaojuan Yang, Liqiang Wu
The NAPRT-induced increase in NAD+ levels was proposed as a mechanism contributing to hepatocellular carcinoma (HCC) resistance to NAMPT inhibitors. Thus, concurrently targeting NAMPT and NAPRT could be considered to overcome drug resistance. A BRD4 inhibitor downregulates the expression of NAPRT in HCC, and the combination of NAMPT inhibitors with BRD4 inhibitors simultaneously blocks NAD+ generation via salvage and the PH synthesis pathway. Moreover, the combination of the two agents significantly downregulated the expression of tumor-promoting genes and strongly promoted apoptosis...
April 26, 2024: European Journal of Medicinal Chemistry
https://read.qxmd.com/read/38690456/successful-pregnancy-and-fetal-outcomes-following-brentuximab-vedotin-for-early-relapsed-classic-hodgkin-lymphoma-after-autologous-stem-cell-transplant
#5
Akari Goto, Chisa Fujita, Hiroto Horiguchi, Satoshi Iyama, Masayoshi Kobune
Brentuximab vedotin (BV), an anti-CD30 antibody with monomethyl auristatin E conjugate, has shown clinical effects against relapsed/refractory classic Hodgkin lymphoma (cHL) and hence is widely used in the clinical setting. We report a special clinical case of successful pregnancy and fetal outcome in a patient with cHL who achieved long-term remission with BV for early relapse after an autologous stem cell transplant (auto-SCT). A 27-year-old woman with advanced cHL achieved complete response (CR) after six cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) regimen...
March 2024: Curēus
https://read.qxmd.com/read/38689512/prevalence-of-people-living-with-multidrug-resistant-hiv-and-limited-treatment-options-in-spain
#6
JOURNAL ARTICLE
Josep M Llibre, Federico García, José Luis Blanco, Esmeralda Palmier Peláez, Álvaro Mena de Cea, Luis López Cortés, Marta Montero Alonso, Miguel Pascual Bernáldez, Melanie Schroeder, Silvia Esteban Sánchez, Felipe Rodríguez Alcántara
OBJECTIVES: Our aim was to determine the prevalence and characteristics of people with HIV on antiretroviral therapy (ART) with multidrug resistance (MDR; confirmed resistance to three or more [or resistance to two or more plus contraindication to one or more] core ART classes) and limited treatment options (LTOs) in Spain. METHODS: This was an observational, retrospective, multicentre, cross-sectional chart review study undertaken in five reference Spanish centres...
April 30, 2024: HIV Medicine
https://read.qxmd.com/read/38688632/high-tailored-anal-canal-radiotherapy-hit-art-outcomes-of-a-10-year-single-center-clinical-experience
#7
JOURNAL ARTICLE
Stefania Manfrida, Bruno Fionda, Silvia Mariani, Viola DE Luca, Roberta Bertolini, Brunella Barbaro, Giuditta Chiloiro, Vincenzo Frascino, Luca Tagliaferri, Maria Antonietta Gambacorta
BACKGROUND/AIM: The current standard for anal cancer treatment is essentially a 'one size fits all' approach where the dose of radiotherapy is similar whether the tumor is very small or very large. Trials are ongoing to evaluate dose de-escalation or escalation in localized disease depending on tumor size. The aim of the study was to assess results of a personalized approach involving dose stratification by stage and boost dose adjusted according to tumor early response. PATIENTS AND METHODS: We retrospectively reviewed squamous cell anal cancer (SCAC) patients treated between 2011 and 2021 by long-course intensity-modulated radiotherapy (IMRT) and concomitant chemotherapy (CT); a sequential boost could be administered by IMRT or interventional radiotherapy (IRT) to obtain a total equivalent dose in 2 Gy (EQD2) of 54-60 Gy...
2024: In Vivo
https://read.qxmd.com/read/38687412/clinical-features-of-immature-leukemias-in-children
#8
JOURNAL ARTICLE
Daichi Sajiki, Nao Yoshida, Hideki Muramatsu, Kimiyoshi Sakaguchi, Naoko Maeda, Norifumi Yokoyama, Yuji Miyajima, Makito Tanaka, Yoshiyuki Takahashi, Asahito Hama
Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL), mixed phenotypic acute leukemia (MPAL), and acute myeloid leukemia with minimal differentiation (AML-M0) all originate from immature hematopoietic progenitor cells and have a poor prognosis. We investigated the clinical characteristics of these immature leukemias in 17 children (ETP-ALL: 8, MPAL: 5, AML-M0: 4) at seven institutions. Clinical and laboratory findings were comparable across disease types. Eleven and six patients received ALL- and AML-oriented induction chemotherapy, with six and four achieving complete remission (CR), respectively...
April 30, 2024: International Journal of Hematology
https://read.qxmd.com/read/38686051/mir-200b-3p-accelerates-progression-of-pituitary-adenomas-by-negatively-regulating-expression-of-reck
#9
JOURNAL ARTICLE
Xiaoxi Wang, Yanfei Jia, Qiang Li, Qiang Yang, Yingfeng Liu, Beifeng Wei, Xiang Niu, Yinjie Zhang, Xiaodong Luo, Ziyu Zhao, Peng Wang
MicroRNA (miR)-200b-3p has been associated with many tumors, but its involvement in pituitary adenoma is unclear. This study investigated the molecular mechanism underlying miR-200b-3p regulation in pituitary adenomas to provide a theoretical basis for treatment. Bioinformatics was used to analyze pituitary adenoma-related genes and screen new targets related to RECK and miRNA. As well, the relationship between miR-200b-3p and RECK protein was verified using a double-luciferase reporter gene assay. The expression of miR-200b-3p in clinical samples was analyzed by in situ hybridization...
2024: Oncology Research
https://read.qxmd.com/read/38680863/efficacy-and-safety-of-venetoclax-plus-hypomethylating-agents-in-relapsed-refractory-acute-myeloid-leukemia-a-multicenter-real-life-experience
#10
JOURNAL ARTICLE
Francesco Angotzi, Federica Lessi, Matteo Leoncin, Carla Filì, Mauro Endri, Albana Lico, Andrea Visentin, Stefano Pravato, Anna Candoni, Livio Trentin, Carmela Gurrieri
Venetoclax (VEN) has been shown to play a synergistic effect in combination with hypomethylating agents (HMAs) in the frontline treatment of acute myeloid leukemia (AML). However, the potential role of this therapy in the relapsed/refractory (R/R) AML setting, still needs to be further unveiled. The aim of the current study was to retrospectively outline the safety profile, response and survival outcomes of R/R AML patients treated with VEN in association with HMAs. Clinical, biological, and molecular data were collected from 57 patients with R/R AML treated with VEN combined with azacitidine or decitabine between 2018 and 2023...
2024: Frontiers in Oncology
https://read.qxmd.com/read/38679849/juvenile-xanthogranuloma-manifesting-with-lch-associated-neurodegenerative-disease-like-radiological-findings
#11
JOURNAL ARTICLE
Tomoo Daifu, Katsutsugu Umeda, Atsushi Yokoyama, Takeshi Yoshida, Satoshi Saida, Itaru Kato, Hidefumi Hiramatsu, Ko Kudo, Yoshihisa Higuchi, Junko Takita
Here, we describe two patients with juvenile xanthogranuloma (JXG) manifesting with Langerhans cell histiocytosis (LCH)-associated neurodegenerative disease (ND)-like radiological findings. One patient showed typical radiological abnormalities at onset, which worsened with progressing central nervous system symptoms 7 years after LCH-oriented chemotherapy. Another showed spontaneous regression of clinical symptoms, with a transient radiological change 1 year after salvage chemotherapy for recurrence of JXG...
April 28, 2024: Pediatric Blood & Cancer
https://read.qxmd.com/read/38673429/oncologic-outcomes-of-salvage-abdominoperineal-resection-for-anal-squamous-cell-carcinoma-initially-managed-with-chemoradiation
#12
JOURNAL ARTICLE
Roni Rosen, Felipe F Quezada-Diaz, Mithat Gönen, Georgios Karagkounis, Maria Widmar, Iris H Wei, J Joshua Smith, Garrett M Nash, Martin R Weiser, Philip B Paty, Andrea Cercek, Paul B Romesser, Francisco Sanchez-Vega, Mohammad Adileh, Diana Roth O'Brien, Carla Hajj, Vonetta M Williams, Marina Shcherba, Ping Gu, Christopher Crane, Leonard B Saltz, Julio Garcia Aguilar, Emmanouil Pappou
Background: Abdominoperineal resection (APR) has been advocated for persistent or recurrent disease after failure of chemoradiation (CRT) for anal squamous cell cancer (SCC). Treatment with salvage APR can potentially achieve a cure. This study aimed to analyze oncological outcomes for salvage APR in a recent time period at a comprehensive cancer center. Methods: A retrospective review of all patients who underwent APR for biopsy-proven persistent or recurrent anal SCC between 1 January 2007 and 31 December 2020 was performed...
April 9, 2024: Journal of Clinical Medicine
https://read.qxmd.com/read/38672276/atorvastatin-treatment-significantly-increased-the-concentration-of-bone-marrow-derived-mononuclear-cells-and-transcutaneous-oxygen-pressure-and-lowered-the-pain-scale-after-bone-marrow-cells-treatment-in-patients-with-no-option-critical-limb-ischaemia
#13
JOURNAL ARTICLE
Jan Kyselovic, Adriana Adamičková, Andrea Gažová, Simona Valášková, Nikola Chomaničová, Zdenko Červenák, Juraj Madaric
BACKGROUND: The present study investigated the outcomes and possible predictive factors of autologous bone marrow cells (BMCs) therapy in patients with "no-option" critical limb ischaemia (CLI). It was focused on exploring the clinical background and prior statin and renin-angiotensin system (RAS)-acting agents pharmacotherapy related to the therapeutic efficacy of BMCs treatment. METHODS: In the present study, we reviewed thirty-three patients (mean age 64.9 ± 10 years; 31 males) with advanced CLI after failed or impossible revascularisation, who were treated with 40 mL of autologous BMCs by local intramuscular application...
April 22, 2024: Biomedicines
https://read.qxmd.com/read/38669142/environmental-purines-decrease-pseudomonas-aeruginosa-biofilm-formation-by-disrupting-c-di-gmp-metabolism
#14
JOURNAL ARTICLE
Corey Kennelly, Peter Tran, Arthur Prindle
Cyclic di-guanosine monophosphate (c-di-GMP) is a bacterial second messenger that governs the lifestyle switch between planktonic and biofilm states. While substantial investigation has focused on the proteins that produce and degrade c-di-GMP, less attention has been paid to the potential for metabolic control of c-di-GMP signaling. Here, we show that micromolar levels of specific environmental purines unexpectedly decrease c-di-GMP and biofilm formation in Pseudomonas aeruginosa. Using a fluorescent genetic reporter, we show that adenosine and inosine decrease c-di-GMP even when competing purines are present...
April 25, 2024: Cell Reports
https://read.qxmd.com/read/38666789/impact-of-blood-salvage-therapy-during-oncologic-liver-surgeries-on-allogenic-transfusion-events-survival-and-recurrence-an-ambidirectional-cohort-study
#15
JOURNAL ARTICLE
Liav Lugassy, Samuel Marion, Frédéric Balthazar, Sonia Gabriela Cheng Oviedo, Yves Collin
INTRODUCTION: The use of autologous blood transfusions in oncologic surgeries is somewhat controversial due to the potential risk of disease dissemination through the salvage process. On the other hand, autologous blood transfusion can prevent the potential negative effects of allogenic blood transfusions and reduce use of valuable resources. METHODS: This study included 106 adult patients who underwent oncologic liver surgery at our institution between December 2015 and June 2019...
April 26, 2024: International Journal of Surgery
https://read.qxmd.com/read/38662205/daratumumab-and-venetoclax-combined-with-cage-for-late-r-r-t-all-lbl-patients-single-arm-open-label-phase-i-study
#16
JOURNAL ARTICLE
Hui Shi, Fan Yang, Miaomiao Cao, Teng Xu, Peihao Zheng, Yuelu Guo, Guoai Su, Shaomei Feng, Ruiting Li, Rui Liu, Haidi Liu, Lixia Ma, Xiaoyan Ke, Kai Hu
The prognosis of patients diagnosed with relapsed or refractory (R/R) T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) has consistently been unsatisfactory, with limited treatment options. As reports, the CAG regimen can serve as a salvage treatment for R/R T-ALL/LBL, but there remains a subset of patients who do not benefit from it. Recent studies have indicated that daratumumab (Dara) and venetoclax (Ven) may offer promising therapeutic benefits for T-ALL/LBL. In light of these findings, we conducted a safety and efficacy evaluation of the enhanced treatment regimen, combining Dara and Ven with aclarubicin, cytarabine, granulocyte colony-stimulating factor, and etoposide (CAGE), in patients suffering from R/R T-ALL/LBL...
April 25, 2024: Annals of Hematology
https://read.qxmd.com/read/38660343/achieving-complete-metabolic-response-in-stage-iv-lung-adenocarcinoma-with-chemotherapy-nivolumab-ipilimumab-and-salvage-sbrt-a-case-report
#17
Salvador Gamez Casado, Javier David Benitez Fuentes, Beatriz Álvarez Rodríguez, Gema García Ledo
Oncogene-negative, PDL1-negative metastatic non-small cell lung cancer (NSCLC) presents significant treatment challenges due to its complexity and resistance to conventional therapies. The case report presented addresses a 55-year-old male patient with oncogene-negative, PDL1-negative stage IV lung adenocarcinoma, showcasing an exceptional complete metabolic response to a multimodality treatment combining double immune checkpoint inhibition (ICI) and chemotherapy, followed by salvage stereotactic body radiotherapy (SBRT)...
April 2024: Respirology Case Reports
https://read.qxmd.com/read/38659569/a-deeper-depth-of-response-after-salvage-therapy-improves-outcomes-of-autologous-stem-cell-transplantation-in-relapsed-lymphoma-and-the-feasibility-of-non-controlled-rate-freezing-of-peripheral-blood-stem-cells
#18
JOURNAL ARTICLE
Saif Ur Rab, Mussadique Ali, Uzma Rasool Mahar, Bushra Ahsan, Usman Ahmad, Muhammad Tariq Mahmood, Neelam Siddiqui, Syed W Bokhari
Background High-dose chemotherapy followed by autologous stem cell transplantation is considered a standard treatment approach for patients with relapsed Hodgkin's lymphoma (HL) and non-Hodgkin lymphoma (NHL). The goal of autologous stem cell transplant in relapsed lymphoma is to achieve long-term disease control, i.e., cure, in contrast to disorders like multiple myeloma, where it only prolongs the duration of remission, progression-free survival, and improves the quality of life. Published outcomes of high-dose therapy and ASCT and the impact of different factors affecting survival in low- to middle-income countries are very limited...
March 2024: Curēus
https://read.qxmd.com/read/38658605/risk-factors-and-predictive-nomograms-for-bedside-emergency-endoscopic-treatment-following-endotracheal-intubation-in-cirrhotic-patients-with-esophagogastric-variceal-bleeding
#19
JOURNAL ARTICLE
Ajuan Zeng, Yangjie Li, Lingna Lyu, Shibin Zhang, Yuening Zhang, Huiguo Ding, Lei Li
Data on emergency endoscopic treatment following endotracheal intubation in patients with esophagogastric variceal bleeding (EGVB) remain limited. This retrospective study aimed to explore the efficacy and risk factors of bedside emergency endoscopic treatment following endotracheal intubation in severe EGVB patients admitted in Intensive Care Unit. A total of 165 EGVB patients were enrolled and allocated to training and validation sets in a randomly stratified manner. Univariate and multivariate logistic regression analyses were used to identify independent risk factors to construct nomograms for predicting the prognosis related to endoscopic hemostasis failure rate and 6-week mortality...
April 24, 2024: Scientific Reports
https://read.qxmd.com/read/38658209/high-dose-chemotherapy-with-autologous-stem-cell-transplant-for-patients-with-advanced-germ-cell-tumors-real-world-evidence-from-a-tertiary-cancer-center-in-brazil
#20
JOURNAL ARTICLE
Gabriel Berlingieri Polho, Mateus Trinconi Cunha, Maiana Hamdan Melo Coelho, Jamile Almeida-Silva, Cassio Murilo Hidalgo Filho, Erick Menezes Xavier, Nathalia de Souza Crusoe, Marcelo Junqueira Atanazio, Vitor Fiorin de Vasconcellos, Vivian Naomi Horita, Guilherme Fialho Freitas, David Queiroz Muniz, Vanderson Rocha, Jose Mauricio Mota
BACKGROUND: High-dose chemotherapy followed by stem cell transplant (HDCT) is potentially curative for patients with refractory germ cell tumors (rGCT). There is scarce real-world data supporting its implementation in low- and middle-income countries. We described the experience of our tertiary cancer center in Sao Paulo, Brazil. METHODS: We identified male patients ≥18 years-old with rGCT referred to HDCT after board discussion. Clinical data, including delays in HDCT protocol, were extracted from medical records, and survival outcomes were estimated using the Kaplan-Meier method...
March 24, 2024: Clinical Genitourinary Cancer
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