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PURPOSE: Older survivors of leukemia and lymphoma often experience long-term effects of chemotherapy. We described common concerns related to their cancer and treatment in older survivors of leukemia and non-Hodgkin lymphoma (NHL) and assessed correlates of these concerns. METHODS: We utilized data from the Womens Health Initiative (WHI) Life and Longevity After Cancer (LILAC) study that recruited post-menopausal women aged 50-79. Participants diagnosed with leukemia and NHL were included (n = 420). They were asked about 14 areas of current concerns related to their cancer and treatment and to rate each from 0 (no concern) to 2 (major concern), with total scores ranging from 0 to 28. Linear regression was used to assess factors correlated with the concern score, and logistic regression for factors correlated with the three most common concerns. RESULTS: Mean age at assessment was 81 years (range 69-99); 72% reported at least one concern, and median concern score among these survivors was 3.5 (Q1-Q3 2-5). Factors significantly correlated with concern scores were sadness, pain, distress, higher prior symptom count, and loneliness (all p

Nanotechnology has become integral in the improvement of methodology used to identify and treat various cancers. Nanoparticles (NPs) exhibit unique features that enhance sensitivity and selectivity and subsequently reduce the time required to detect early-stage cancer through biomarkers. NPs improve the therapeutic efficiency of anticancer agents when compared with conventional methods, such as chemotherapy, and thereby eliminate toxicity and side effects, which helps improve the stability, solubility, half-life, and tumor aggregation of an anticancer drug. This also helps expedite the treatment cycle by enabling a real-time assessment, quickly circumventing various biological barriers, improving vectorization and delivery, overcoming drug resistance, and developing various paths for the manufacturing of new synthetic vaccines. Nanomedicine has usually involved studies on solid-state cancers because it can increase the cell permeability and retention effect experienced within the tumor areas to improve regional accumulation and efficacy. Nanomedicine for leukemia and lymphoma is addressed differently from solid-state cancers because of the absence of the enhanced permeability and retention effect.Nevertheless, nanomedicine has enabled the development of various modern innovative techniques for simple and noninvasive procedures for prior analysis of cancers with subsequent diffuse tumor treatment. In this assessment, we consider various unique constructs on NPs that can predominantly enhance therapeutic treatment over diffused tumors by increasing control, from preclinical testing to medicinal trials. Nanotechnology combines nanodiagnostics, nanotherapeutics, and nanotheranostics for improved imaging and diagnoses of early stage cancers. Furthermore, the primacy of nanoplatforms has been discussed for an invaluable position in this blended method. There are many types of NPs, such as organic, inorganic, and hybrid NPs. The minute size of NPs makes them ideal for intracellular uptake, and the large surface area ratio allows functional interactions with various compounds. This review also covers targeting cancerous cells via inducing lysosomal autophagy using gold NPs.

Nanotechnology has become integral in the improvement of methodology used to identify and treat various cancers. Nanoparticles (NPs) exhibit unique features that enhance sensitivity and selectivity and subsequently reduce the time required to detect early-stage cancer through biomarkers. NPs improve the therapeutic efficiency of anticancer agents when compared with conventional methods, such as chemotherapy, and thereby eliminate toxicity and side effects, which helps improve the stability, solubility, half-life, and tumor aggregation of an anticancer drug. This also helps expedite the treatment cycle by enabling a real-time assessment, quickly circumventing various biological barriers, improving vectorization and delivery, overcoming drug resistance, and developing various paths for the manufacturing of new synthetic vaccines. Nanomedicine has usually involved studies on solid-state cancers because it can increase the cell permeability and retention effect experienced within the tumor areas to improve regional accumulation and efficacy. Nanomedicine for leukemia and lymphoma is addressed differently from solid-state cancers because of the absence of the enhanced permeability and retention effect. Nevertheless, nanomedicine has enabled the development of various modern innovative techniques for simple and noninvasive procedures for prior analysis of cancers with subsequent diffuse tumor treatment. In this assessment, we consider various unique constructs on NPs that can predominantly enhance therapeutic treatment over diffused tumors by increasing control, from preclinical testing to medicinal trials. Nanotechnology combines nanodiagnostics, nanotherapeutics, and nanotheranostics for improved imaging and diagnoses of early stage cancers. Furthermore, the primacy of nanoplatforms has been discussed for an invaluable position in this blended method. There are many types of NPs, such as organic, inorganic, and hybrid NPs. The minute size of NPs makes them ideal for intracellular uptake, and the large surface area ratio allows functional interactions with various compounds. This review also covers targeting cancerous cells via inducing lysosomal autophagy using gold NPs. [ABSTRACT FROM AUTHOR]

Access to reliable, up-to-date information and resources can assist individuals managing and living with cancer. The Leukemia & Lymphoma Society, through its Information Resource Center, provides personalized information and support to individuals affected by blood cancer. To examine its value and impact, we conducted qualitative interviews (n = 18) and an online survey of patients and caregivers (N = 515) after they talked with an Information Resource Center Information Specialist by phone, with a follow-up survey about 6 months later. Respondents most commonly contacted the Information Resource Center to get referrals to support programs (40.4%) and to obtain information about getting a second opinion (36.5%) and financial assistance (36.2%). After talking with an Information Specialist, respondents felt more hopeful (85.9%), more confident in managing care (82.9%), and more knowledgeable about their diagnosis (49.5%) and financial resources (42.4%). After speaking with an Information Specialist, respondents changed how they advocated for themselves/loved one (23.8%), changed how they communicated with doctors/other providers and family/friends (both 15.9%), received financial assistance (22.2%), and took other actions. Among respondents who took actions, most said that the conversation(s) had positively impacted the action. Respondents who spoke with an Information Specialist more than once were more likely to report positive impacts, including changing how they advocate for themselves/loved one and communicate with providers (both p < 0.05). Respondents diagnosed more recently were also more likely to report positive impact, including changing the way they communicate with providers (p < 0.05). Findings highlight the value of cancer helplines and suggest ways they can be most effective. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T cell therapies targeting B cell-restricted antigens CD19, CD20, or CD22 can produce potent clinical responses for some B cell malignancies, but relapse remains common. Camelid single-domain antibodies (sdAbs or nanobodies) are smaller, simpler, and easier to recombine than single-chain variable fragments (scFvs) used in most CARs, but fewer sdAb-CARs have been reported. Thus, we sought to identify a therapeutically active sdAb-CAR targeting human CD22. Immunization of an adult Llama glama with CD22 protein, sdAb-cDNA library construction, and phage panning yielded >20 sdAbs with diverse epitope and binding properties. Expressing CD22-sdAb-CAR in Jurkat cells drove varying CD22-specific reactivity not correlated with antibody affinity. Changing CD28- to CD8-transmembrane design increased CAR persistence and expression in vitro . CD22-sdAb-CAR candidates showed similar CD22-dependent CAR-T expansion in vitro, although only membrane-proximal epitope targeting CD22-sdAb-CARs activated direct cytolytic killing and extended survival in a lymphoma xenograft model. Based on enhanced survival in blinded xenograft studies, a lead CD22sdCAR-T was selected, achieving comparable complete responses to a benchmark short linker m971-scFv CAR-T in high-dose experiments. Finally, immunohistochemistry and flow cytometry confirm tissue and cellular-level specificity of the lead CD22-sdAb. This presents a complete report on preclinical development of a novel CD22sdCAR therapeutic., Competing Interests: CD22-nanobody binding elements used in this work were disclosed in provisional patent filing US 2023/0265185 A1 and other provisional filings by the NRC. The authors declare no competing interests., (Crown Copyright © 2024.)

Background As relapsed disease is frequently the first target of newly developed therapies, it is vital to address the difficulty in demonstrating the efficacy of new drugs for relapsed malignancy in randomized phase 3 trials. Methods We analyzed the approved indications, target populations, and development status of post-marketing confirmatory trials of all oncology-related drugs that were granted accelerated approval for both hematological and solid malignancies. Furthermore, we searched for randomized phase 3 trials for adult patients with relapsed lymphoid malignancy, other than chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). Results Thirty-one (81.6%) of the 38 hematological indications and 23 (53.5%) of the 43 solid malignancy indications were in the relapsed settings. The target population of post-marketing studies was different from the approved indication in 18 (47.4%) of 38 hematological indications and 11 (25.6%) of 43 solid malignancy indications; all 18 hematological indications involved relapsed settings. Improved time-to-event outcome for relapsed patients was the primary endpoint in 6 (19.3%) of the 31 relapsed hematological indications. In 4 published studies of relapsed lymphoid malignancy, the medication significantly improved outcomes. From 33 trials listed at Clinicaltrials.gov, 2 were positive and 13 were negative. Five out of the 13 negative trials were terminated due to poor accrual. Conclusion Our analysis indicates that drug approval based on phase 3 trials is more challenging for relapsed hematological malignancies than for solid malignancies. Therefore, determining proper evaluation methods for the efficacy and safety of drugs for relapsed malignancy, without randomized trials, is important. [ABSTRACT FROM AUTHOR]

Rasburicase is a novel drug used during the management of tumor lysis syndrome. In countries with limited resources, it is frequently given at a lower dose and only for the treatment of established tumor lysis syndrome and not as prophylaxis. A retrospective study was conducted in the department of pediatric oncology at a tertiary referral oncology center in south India to analyze the use of rasburicase over the past 3 years. Data of all the 18 children (< 14 years of age) who were given rasburicase for the management of hyperuricemia were collected and analyzed. With a mean rasburicase dose of 0.085 mg/kg, hyperuricemia was managed efficiently without the need for a hemodialysis in 16 children (88.8 %). The fall in mean serum uric acid levels after the administration of a single dose of rasburicase at 4, 24, and 48 hours was 31.18 %, 64.8 %, and 74.5 %, respectively. Rasburicase efficiently decreases the uric acid levels to a normal level within a short period. In resource-limited settings, rasburicase at a lower dose is a promising option for managing hyperuricemia in the event of a tumor lysis syndrome. [ABSTRACT FROM AUTHOR]

Cancer- and treatment-related side effects in patients with childhood cancer may cause limitations in motor performance affecting activities of daily living (ADLs). Data focusing on long-term effects are available, but little is known with regard to the short-term perspective. Therefore, the purpose of this study was to assess muscle strength performance and quality of life (QoL) in children and adolescents with cancer at the beginning of primary treatment. Forty children and adolescents aged 5–18 years (mean: 11.39 ± 4.08 years) with different types of childhood cancer were enrolled. On average 36 ± 20.5 days after diagnosis, strength performance in 7 muscle groups was assessed by handheld dynamometry. KINDL questionnaires were completed to evaluate QoL (children's self-report and parents' report). All parameters were compared with age- and gender-matched reference values. Patients with childhood cancer showed significantly lower strength values in all muscle groups (P< .01) compared with age- and gender-matched controls. Most affected were the lower extremities, with a −57.1% ± 10.4%, median: −59.2%, minimum: −75.4%, maximum: −41.4% percentage deviation in knee flexion from healthy peers. Children themselves and parents assessed total QoL significantly below age- and gender-matched reference values (P< .01). Correlation between elbow flexion and self-reported QoL was detected. Broader correlations were found for the parents' report. Muscle weakness and decreased QoL in children and adolescents seem to persist already at the beginning of anticancer treatment. This underlines the need of counteracting measures, such as exercise intervention programs, starting as early as possible during the treatment process. Efforts on this topic are currently being carried out by our group. [ABSTRACT FROM PUBLISHER]

Lymphoid malignancies are characterized by an accumulation of genetic lesions that act co-operatively to perturb signaling pathways and alter gene expression programs. The Janus kinases (JAK)–signal transducers and activators of transcription (STATs) pathway is one such pathway that is frequently mutated in leukemia and lymphoma. In response to cytokines and growth factors, a cascade of reversible tyrosine phosphorylation events propagates the JAK–STAT pathway from the cell surface to the nucleus. Activated STAT family members then play a fundamental role in establishing the transcriptional landscape of the cell. In leukemia and lymphoma, somatic mutations have been identified in JAK and STAT family members, as well as, negative regulators of the pathway. Most recently, inactivating mutations in the protein tyrosine phosphatase (PTP) genes PTPN1 (PTP1B) and PTPN2 (TC-PTP) were sequenced in B cell lymphoma and T cell acute lymphoblastic leukemia (T-ALL) respectively. The loss of PTP1B and TC-PTP phosphatase activity is associated with an increase in cytokine sensitivity, elevated JAK–STAT signaling, and changes in gene expression. As inactivation mutations in PTPN1 and PTPN2 are restricted to distinct subsets of leukemia and lymphoma, a future challenge will be to identify in which cellular contexts do they contributing to the initiation or maintenance of leukemogenesis or lymphomagenesis. As well, the molecular mechanisms by which PTP1B and TC-PTP loss co-operates with other genetic aberrations will need to be elucidated to design more effective therapeutic strategies. [ABSTRACT FROM AUTHOR]

Interferon regulatory factor 4 (IRF4) and IRF8 are critical regulators of immune system development and function. In B lymphocytes, IRF4 and IRF8 have been shown to control important events during their development and maturation including pre-B cell differentiation, induction of B cell tolerance pathways, marginal zone B cell development, germinal center reaction and plasma cell differentiation. Mechanistically, IRF4 and IRF8 are found to function redundantly to control certain stages of B cell development, but in other stages, they function nonredundantly to play distinct roles in B cell biology. In line with their essential roles in B cell development, deregulated expressions of IRF4 and IRF8 have been associated to the pathogenesis of several B cell malignancies and diseases. Recent studies have elucidated diverse transcriptional networks regulated by IRF4 and IRF8 at distinct B cell developmental stages and related malignancies. In this review we will discuss the recent advances for the roles of IRF4 and IRF8 during B cell development and associated diseases. [ABSTRACT FROM AUTHOR]

The phosphoinositide 3-kinase (PI3K) pathway is a central signal transduction axis controlling normal B cell homeostasis and activation in humoral immunity. The p110δ PI3K catalytic subunit has emerged as a critical mediator of multiple B cell functions. The activity of this pathway is regulated at multiple levels, with inositol phosphatases PTEN and SHIP both playing critical roles. When deregulated, the PI3K pathway can contribute to B cell malignancies and autoantibody production. This review summarizes current knowledge on key mechanisms that activate and regulate the PI3K pathway and influence normal B cell functional responses including the development of B cell subsets, antigen presentation, immunoglobulin isotype switch, germinal center responses, and maintenance of B cell anergy. We also discuss PI3K pathway alterations reported in select B cell malignancies and highlight studies indicating the functional significance of this pathway in malignant B cell survival and growth within tissue microenvironments. Finally, we comment on early clinical trial results, which support PI3K inhibition as a promising treatment of chronic lymphocytic leukemia. [ABSTRACT FROM AUTHOR]

Children treated for cancer face the risk of complications later in life, including pulmonary dysfunction. The objective of this study was to evaluate frequency and severity of pulmonary complications in survivors of childhood leukemia and lymphoma treated with chemotherapy alone or combined with radiotherapy. Seventy cancer survivors of hematological malignancies were evaluated for pulmonary complications through history taking, chest examination, high-resolution computed tomography (HRCT) chest, and pulmonary function testing (PFTs). Although most survivors were not clinically compromised, the spectrum of impaired PFTs included obstructive pattern (14.3%%), restrictive pattern (5.7%%), and mixed pattern (20%%). Significant pulmonary dysfunction was seen in children older than 10 years of age ( P == .003), and in patients treated with combined chemotherapy and radiotherapy (72.7%%) compared with those treated with chemotherapy alone (25%%) ( P == .001). Cumulative dose of bleomycin was significantly associated with abnormal PFTs ( P == .04). Multivariate analysis revealed methotrexate therapy as significant predictor of abnormal PFTs ( P == .002). Male patients who received combined therapy showed higher frequency of restrictive, obstructive lung disease, abnormal respiratory reactance, and peripheral airway disease ( P == .007, P == .04, P == .002, P == .003, P == .05, respectively). Those with abnormal CT findings ( n == 14) had lower forced vital capacity (FVC%%), forced expiratory volume in 1 second (FEV1%%), and peak expiratory flow (PEF%%) when compared to cases with normal CT ( P == .001, P <0.001, P == .001, respectively). Subclinical pulmonary function abnormalities are found in survivors of childhood hematological malignancies previously treated and off therapy. Pulmonary dysfunction is more evident with combined chemotherapy and radiotherapy, bleomycin, and methotrexate are the most incriminated chemotherapeutic agents, and males are at higher risk than females; therefore a specific and extended follow-up is warranted. [ABSTRACT FROM AUTHOR]

Abstract: Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase that plays important regulatory roles in several basic cellular activities. During normal development, FAK is a critical mediator of the integrin signaling cascade, which modulates cell proliferation, apoptosis, adhesion, spreading and migration. Importantly, FAK overexpression is found in a large number of cancer types and FAK expression levels generally correlate with increased tumor malignancy. Though FAK has been a popular potential target for treatment of solid tumors, its roles in leukemias and lymphomas have not been well defined. Here, I briefly summarize the multifaceted functions of FAK in tumor progression, and discuss current efforts and exciting future directions of using RNAi-mediated knockdown of FAK as a potential therapy against leukemia and lymphomas. [Copyright &y& Elsevier]

Data mining is defined as finding hidden information in a database. Classification is a data mining (machine learning) technique used to predict group membership for data instances. In this research, lymphoma and leukemia cancer detection based on the Support Vector Machine- One against One (SVM-OAO) and the Support Vector Machine -- One against All (SVM-OAA) is estimated. For estimating the cancer classifications accurately, information gain ratio is highly effective ranking scheme, and gene subset selection is done using Canberra distance metrics. SVM-OAO and SVM-OAA are used as good classifiers. Many other gene importance ranking schemes and classifiers may also be used in this approach. Classification involves four steps. In the first step, the top genes are selected using a feature importance ranking scheme. In the second step, the gene subset is generated using distance metrics. In the third step, the classification capability of all genes within the subset is classified by a good classifier. In the fourth step, the top genes selected using ranking schemes without subset selection) is classified by a same classifier. A K-nearest neighbor algorithm is applied to fill those missing values. This research suggests a unified criterion for gene ranking and subset selection of genes. In the Micro array technology to find specific cancer related genes that can be used to diagnose and predict cancer stage. [ABSTRACT FROM AUTHOR]

Background: The genome association databases provide valuable clues to identify novel targets for cancer diagnosis and therapy. Genes harboring phenotype-associated polymorphisms for neoplasm traits can be identified using diverse bioinformatics tools. The recent availability of various protein expression datasets from normal human tissues, including the body fluids, enables for baseline expression profiling of the cancer secretome. Chemoinformatics approaches can help identify drug-like compounds from the protein 3D structures., Materials and Methods: The National Center for Biotechnology Information (NCBI) Phenome Genome Integrator (PheGenI) tool was enriched for neoplasm-associated traits. The neoplasm genes were characterized using diverse bioinformatics tools for pathways, gene ontology, genome-wide association, protein expression and functional class. Chemogenomics analysis was performed using the canSAR protein annotation tool., Results: The neoplasm-associated traits segregated into 1,305 genes harboring 2,837 single nucleotide polymorphisms (SNPs). Also identified were 65 open reading frames (ORFs) encompassing 137 SNPs. The neoplasm genes and the associated SNPs were classified into distinct tumor types. Protein expression in the secretome was seen for 913 of the neoplasm-associated genes, including 17 novel uncharacterized ORFs. Druggable proteins, including enzymes, transporters, channel proteins and receptors, were detected. Thirty-four novel druggable lead genes emerged from these studies, including seven cancer lead targets. Chemogenomics analysis using the canSAR protein annotation tool identified 168 active compounds (<1 μM) for the neoplasm genes in the body fluids. Among these, 7 most active lead compounds with drug-like properties (1-600 nM) were identified for the cancer lead targets, encompassing enzymes and receptors., Conclusion: Over seventy percent of the neoplasm trait-associated genes were detected in the body fluids, such as ascites, blood, tear, milk, semen, urine, etc. Ligand-based druggabililty analysis helped establish lead prioritization. The association of these proteins with diverse cancer types and other diseases provides a framework to develop novel diagnosis and therapy targets., (Copyright© 2015, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.)

Background: Pancreatic cancer, has a very high mortality rate and requires novel molecular targets for diagnosis and therapy. Genetic association studies over databases offer an attractive starting point for gene discovery., Materials and Methods: The National Center for Biotechnology Information (NCBI) Phenome Genome Integrator (PheGenI) tool was enriched for pancreatic cancer-associated traits. The genes associated with the trait were characterized using diverse bioinformatics tools for Genome-Wide Association (GWA), transcriptome and proteome profile and protein classes for motif and domain., Results: Two hundred twenty-six genes were identified that had a genetic association with pancreatic cancer in the human genome. This included 25 uncharacterized open reading frames (ORFs). Bioinformatics analysis of these ORFs identified putative druggable proteins and biomarkers including enzymes, transporters and G-protein-coupled receptor signaling proteins. Secreted proteins including a neuroendocrine factor and a chemokine were identified. Five out of these ORFs encompassed non coding RNAs. The ORF protein expression was detected in numerous body fluids, such as ascites, bile, pancreatic juice, milk, plasma, serum and saliva. Transcriptome and proteome analyses showed a correlation of mRNA and protein expression for nine ORFs. Analysis of the Catalogue of Somatic Mutations in Cancer (COSMIC) database revealed a strong correlation across copy number variations and mRNA over-expression for four ORFs. Mining of the International Cancer Gene Consortium (ICGC) database identified somatic mutations in a significant number of pancreatic patients' tumors for most of these ORFs. The pancreatic cancer-associated ORFs were also found to be genetically associated with other neoplasms, including leukemia, malignant melanoma, neuroblastoma and prostate carcinomas, as well as other unrelated diseases and disorders, such as Alzheimer's disease, Crohn's disease, coronary diseases, attention deficit disorder and addiction., Conclusion: Based on Genome-Wide Association Studies (GWAS), copy number variations, somatic mutational status and correlation of gene expression in pancreatic tumors at the mRNA and protein level, expression specificity in normal tissues and detection in body fluids, six ORFs emerged as putative leads for pancreatic cancer. These six targets provide a basis for accelerated drug discovery and diagnostic marker development for pancreatic cancer., (Copyright© 2015, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.)