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Targeting the DNA Damage Response for Cancer Therapy.

Over the course of long-term evolution, cells have developed intricate defense mechanisms in response to DNA damage; these mechanisms play a pivotal role in maintaining genomic stability. Defects in the DNA damage response pathways can give rise to various diseases, including cancer. The DNA damage response (DDR) system is instrumental in safeguarding genomic stability. The accumulation of DNA damage and the weakening of DDR function both promote the initiation and progression of tumors. Simultaneously, they offer opportunities and targets for cancer therapeutics. This article primarily elucid

Spontaneous Tumor Lysis Syndrome.

Tumor lysis syndrome (TLS) is a hemato-oncological emergency characterized by metabolic and electrolyte imbalances which are associated with disintegrating tumor cells. The syndrome is frequently observed when starting cytotoxic treatment of hematological malignancies, while the incidence of spontaneous tumor lysis prior to the start of tumor therapy is rare. Here, we present a case of spontaneous TLS in a male patient who was referred with unspecific symptoms and suspected metastatic malignancy. He developed acute renal failure before the diagnosis of a high-grade B-cell lymphoma (double hit

ENHANZE® drug delivery technology: a novel approach to subcutaneous administration using recombinant human hyaluronidase PH20

ENHANZE® drug delivery technology is based on the proprietary recombinant human hyaluronidase PH20 enzyme (rHuPH20; Halozyme Therapeutics, Inc.) that facilitates the subcutaneous (SC) delivery of co-administered therapeutics. rHuPH20 works by degrading the glycosaminoglycan hyaluronan (HA), which plays a role in resistance to bulk fluid flow in the SC space, limiting large volume SC drug delivery, dispersion, and absorption. Co-administration of rHuPH20 with partner therapies can overcome administration time and volume barriers associated with existing SC therapeutic formulations, and has been

Hypophosphatemic rickets: diagnosis and treatment.

Hypophosphatemicrickets (HR) represents a heterogeneous group of disorders characterized by renal phosphate wasting, impaired bone mineralization, and skeletal deformities. This narrative review provides an overview of phosphate homeostasis and the molecular mechanisms underlying HR, focusing on the role of Fibroblast Growth Factor 23 (FGF23) in regulating renal phosphate use and vitamin D metabolism. The clinical, biochemical, and genetic features of both FGF23-dependent and -independent forms of HR are discussed, including X-linked hypophosphatemia (XLH), autosomal dominant hypophosphatemic

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… There is ongoing research on targeted therapies, such as ENPP1-Fc enzyme replacement therapy ( 66 ) . … Response of the ENPP1-Deficient Skeletal Phenotype to Oral Phosphate Supplementation and/or Enzyme Replacement Therapy: Comparative Studies in Humans and Mice. J Bone Miner Res. 2021;36(5):942–955. doi: 10.1002/jbmr.4254.. 96. Caballero D, Li Y, Fetene J, Ponsetto J, Chen A, Zhu C, et al. …

Primary Health Care approach to managing chronic kidney disease.

Chronic kidney disease (CKD) is a growing global health issue among ageing populations, driven by increasing diabetes and hypertension. Managing advanced stages of CKD with dialysis or transplants is costly. Early stages often have no symptoms, making early detection important for prevention. Primary care providers can help identify and manage CKD early by performing annual screening for high-risk patients, including blood pressure checks, urine tests for albuminuria or proteinuria and estimating glomerular filtration rate from serum creatinine. For those with CKD, renal protective measures ar

The diagnosis of hypophosphatasia in children as a multidisciplinary effort: an expert opinion.

Hypophosphatasia (HPP) is a rare genetic disorder in which pathogenic variants of the ALPL gene lead to a marked decrease of tissue non-specific alkaline phosphatase (TNSALP) activity. Although HPP is a systemic disorder, its clinical manifestations are more evident on bones, teeth, muscle and central nervous system. The clinical spectrum ranges from severe forms with extreme skeletal deformities, respiratory impairment, seizures, to very mild forms with onset in late adulthood and few clinical signs. The diagnosis can be suspected by measurement of TNSALP activity, but the insufficient awaren

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… Millán JL Narisawa S Lemire I Loisel TP Boileau G Leonarol P Gramatikova S Terkeltaub R Pleshko Camacho N McKee MD Crine P Whyte MP Enzyme replacement therapy for murine hypophosphatasia J Bone Miner Res 2008 23 777 787 10.1359/jbmr.071213 18086009 PMC2652241 17. … Kim I Noh E-S Kim M-S Jang J-H Jeon TY Choi HW Cho SY Six-year clinical outcomes of enzyme replacement therapy for perinatal lethal and infantile hypophosphatasia in Korea: Two case reports Medicine (Baltimore) 2023 102 e32800d 10.1097/MD.0000000000032800 36820543 PMC9907957 24. …

Profile and Management of Toxicity of Selinexor and Belantamab Mafodotin for the Treatment of Triple Class Refractory Multiple Myeloma.

Treatment options are limited for multiple myeloma patients who have developed four/five drug-refractory disease. Selinexor (Sel) and belantamab mafodotin (belamaf) were recently approved by the US FDA for treatment of RRMM. The toxicity profile of these drugs is a concern since these agents are used in patients who have already undergone multiple lines of treatment. In this review, we discuss the toxicity profile and strategies for the management of toxicities of Sel and belamaf for the treatment of RRMM. We conducted a comprehensive literature search on PubMed, Embase, Cochrane, and Clinical

Differences in Inflammation, Treatment, and Outcomes Between Black and Non-Black Patients Hospitalized for COVID-19: A Prospective Cohort Study.

PurposeRacial disparities in coronavirus disease 2019 (COVID-19) outcomes have been described. We sought to determine whether differences in inflammatory markers, use of COVID-19 therapies, enrollment in clinical trials, and in-hospital outcomes contribute to racial disparities between Black and non-Black patients hospitalized for COVID-19.MethodsWe leveraged a prospective cohort study that enrolled 1325 consecutive patients hospitalized for COVID-19, of whom 341 (25.7%) were Black. We measured biomarkers of inflammation and collected data on the use COVID-19-directed therapies, enrollment in

Potential Targeting Mechanisms for Bone-Directed Therapies.

Bone development is characterized by complex regulation mechanisms, including signal transduction and transcription factor-related pathways, glycobiological processes, cellular interactions, transportation mechanisms, and, importantly, chemical formation resulting from hydroxyapatite. Any abnormal regulation in the bone development processes causes skeletal system-related problems. To some extent, the avascularity of cartilage and bone makes drug delivery more challenging than that of soft tissues. Recent studies have implemented many novel bone-targeting approaches to overcome drawbacks. Howe

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… Enzyme replacement therapy targets the GAGs accumulated. Although ERT slightly reduces this storage material in bone, disease progression is not fully corrected [ 42 , 43 ]. 2.3. … In clinical applications, asfotase alpha (Strensig®, Alexion, AstraZeneca, Boston, MA, USA) is a first-line approved enzyme replacement therapy for all patients diagnosed with HPP. …

Review of cancer therapies for the perioperative physician.

Advances in cancer treatments over the past decades combining chemotherapy with novel technologies in immunotherapies, radiation therapies, and interventional radiology have prolonged life expectancy. Patients have more options for treatments of their primary or metastatic diseases. Increased procedural techniques amid an aging population with multiple comorbidities present risks and challenges in the perioperative period.Chemotherapy remains the mainstay of cancer treatment, can be given intraoperatively, and is combined with other treatment modalities. Immunotherapy is particular to cancer c

Adverse Events of Oncologic Immunotherapy and Their Management.

Over the past two decades, immunotherapy has emerged as a promising treatment option for patients with cancer. However, newer versions of immunotherapy, such as checkpoint inhibitors, may be associated with unusual adverse effects (AEs) that can range in severity from mild to life-threatening. Unlike common AEs of conventional chemotherapy, which have a predictable nadir or cyclic pattern after administration, AEs of these newer immunotherapies are variable, depending on the type of immunotherapy, route of administration, and mechanism of action. The onset and resolution of these AEs may be pr

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… The endopeptidases include trypsin, chymotrypsin, and elastase, the exopeptidases are the carboxypeptidases A and B. 2. preparations of various pancreatic extracts are used as enzyme replacement therapy in the clinical management of exocrine pancreatic insufficiency in dogs and cats. …

Targeted synthesis of a trimethoxyphenyltetrahydropyrimidine analogue designed as a DNA intercalator: in silico, multi-spectroscopic, thermodynamic, and in vitro approaches.

Based on the rational design of DNA intercalators and Topo-II inhibitors and taking into consideration the main pharmacophoric features of doxorubicin (Dox) as a reference standard, we theoretically designed novel substituted tetrahydropyrimidine analogues (T1-35). The designed analogues (T1-35) were investigated for their inhibitory potential towards the hybrid DNA and Topo-II target receptor using molecular docking. Interestingly, the theoretically designed analogue T30 with a 3,4,5-trimethoxy phenyl side chain was found to be the superior candidate, achieving a binding score of -7.06 kcal m

Carfilzomib Induced Microangiopathy due to Accumulation With Paxlovid.

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Novel Molecular Therapies and Genetic Landscape in Selected Rare Diseases with Hematologic Manifestations: A Review of the Literature.

Rare diseases affect less than 1 in 2000 people and are characterized by a serious, chronic, and progressive course. Among the described diseases, a mutation in a single gene caused mastocytosis, thrombotic thrombocytopenic purpura, Gaucher disease, and paroxysmal nocturnal hemoglobinuria (KIT, ADAMTS13, GBA1, and PIG-A genes, respectively). In Castleman disease, improper ETS1, PTPN6, TGFBR2, DNMT3A, and PDGFRB genes cause the appearance of symptoms. In histiocytosis, several mutation variants are described: BRAF, MAP2K1, MAP3K1, ARAF, ERBB3, NRAS, KRAS, PICK1, PIK3R2, and PIK3CA. Genes like H

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… Specific treatment, such as enzyme replacement therapy (ERT) using one of the currently available molecules such as imiglucerase, velaglucerase, or taliglucerase, or substrate reduction therapy, is indicated in symptomatic type 1 Gaucher disease. Only ERT is indicated in type 3 Gaucher disease. … Abbreviations AVN | avascular osteonecrosis CD | Castleman disease CDCP1 | CUB domain-containing protein 1 CM | cutaneous mastocytosis CRP | C-reactive protein cTTP | congenital thrombotic thrombocytopenic purpura ERT | enzyme replacement therapy FLH-1 | familial hemophagocytic lymphohistiocytosis …

Multiple myelomas in cats.

Multiple myelomas are uncommon neoplasms of the bone marrow of cats [Weber NA, Tebeau CS (1998) An unusual presentation of multiple myeloma in two cats. Journal of the American Animal Hospital Association34 (6), 477-483]. Nine cats diagnosed with multiple myelomas were retrospectively identified over a 16-year period (1986-2002). Cats with multiple myelomas were older than 7 years (mean age 11.7 years); six males and three females were affected (2.1), but no breed predisposition was evident. Treatment of multiple myelomas consisted of supportive management in the nine cats and anti-neoplastic

Acute kidney injury: pathogenesis and therapeutic interventions.

Acute kidney injury (AKI) is a prevalent clinical condition that is associated with unacceptably high morbidity and mortality, as well as the development of chronic kidney disease (CKD). The pathogenesis of AKI is highly complex and heterogeneous, primarily attributed to metabolic disturbances arising from the disease itself and the administration of medications related to treatment. In recent years, AKI in cancer patients is highly concerned. The emergence of AKI caused injuries and dysfunction of remote organs but also enhanced the health-care costs. It's essential for early recognition of A

Clinical study of Shengxuening tablet combined with rHuEPO for the treatment of renal anemia of maintenance hemodialysis patients.

The aim of the present study was to investigate the clinical effects of Shengxuening tablet (silkworm excrement) combined with recombinant human erythropoietin (rHuEPO) for the treatment of renal anemia of maintenance hemodialysis (MHD) patients. Seventy-two MHD patients with renal anemia were included in the study and randomly divided into the control (n=34) and observation (n=38) groups. Patients in the control group were treated by hypodermic injection of 100-150 U/(kg·w) rHuEPO and patients in the observation group were treated by rHuEPO + 1.0 g t.i.d. p.o. Shengxuening tablet. The two gro

Перепрофилированный активатор Nrf2 диметилфумарат спасает мышцы воспаление и фиброз в отягченной мышиной модели мышечной дистрофии Дученна.

В унаследованных нейромускульных болезнях мышечная дистрофия Дюченна (ДМД) глюкокортикоиды значительно медленнее прогрессируют, но в то же время создают достаточно серьезные побочные эффекты, исключающие применение в значительной части пациентов. Распространяя наши выводы о том, что в результате острого лечения с УЛХ были одобрены многочисленные склерозные препараты, диметилфумарат (ДМФ), спасающая мышечную патологию у молодых мышей Mdx, мы намеревались провести доклиническое тестирование на перевод. Чтобы усилить фенотип болезни у взрослых мышц mdx, у которых обычно нет эквивалентной человече

Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination.

Vitamin C (L-ascorbic acid) has been known as an antioxidant for most people. However, its physiological role is much larger and encompasses very different processes ranging from facilitation of iron absorption through involvement in hormones and carnitine synthesis for important roles in epigenetic processes. Contrarily, high doses act as a pro-oxidant than an anti-oxidant. This may also be the reason why plasma levels are meticulously regulated on the level of absorption and excretion in the kidney. Interestingly, most cells contain vitamin C in millimolar concentrations, which is much highe