Lactate Dehydrogenase Inhibition: Biochemical Relevance and Therapeutical Potential

Laganà, Giuseppina; Barreca, Davide; Calderaro, Antonella; Bellocco, Ersilia

doi:10.2174/0929867324666170209103444

Cited by 36 publications

(13 citation statements)

References 69 publications

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“…Even so, the small size and high polarity of oxamate limit its catalytic activity and permeability. Several N-alkyl-oxamates are synthesized [198]. Further experiments are imperative concerning their inhibitory effects on LDH and anticancer actions.…”

Section: Exploit Novel Small Molecular Compounds Targeting Rosmentioning

confidence: 99%

ROS-Mediated Therapeutic Strategy in Chemo-/Radiotherapy of Head and Neck Cancer

Huang

Pan

2020

Oxidative Medicine and Cellular Longevity

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Head and neck cancer is a highly genetic and metabolic heterogeneous collection of malignancies of the lip, oral cavity, salivary glands, pharynx, esophagus, paranasal sinuses, and larynx with five-year survival rates ranging from 12% to 93%. Patients with head and neck cancer typically present with advanced stage III, IVa, or IVb disease and are treated with comprehensive modality including chemotherapy, radiotherapy, and surgery. Despite advancements in treatment modality and technique, noisome recurrence, invasiveness, and resistance as well as posttreatment complications severely influence survival rate and quality of life. Thus, new therapeutic strategies are urgently needed that offer enhanced efficacy with less toxicity. ROS in cancer cells plays a vital role in regulating cell death, DNA repair, stemness maintenance, metabolic reprogramming, and tumor microenvironment, all of which have been implicated in resistance to chemo-/radiotherapy of head and neck cancer. Adjusting ROS generation and elimination to reverse the resistance of cancer cells without impairing normal cells show great hope in improving the therapeutic efficacy of chemo-/radiotherapy of head and neck cancer. In the current review, we discuss the pivotal and targetable redox-regulating system including superoxide dismutases (SODs), tripeptide glutathione (GSH), thioredoxin (Trxs), peroxiredoxins (PRXs), nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/keap1), and mitochondria electron transporter chain (ETC) complexes and their roles in regulating ROS levels and their clinical significance implicated in chemo-/radiotherapy of head and neck cancer. We also summarize several old drugs (referred to as the non-anti-cancer drugs used in other diseases for a long time) and small molecular compounds as well as natural herbs which effectively modulate cellular ROS of head and neck cancer to synergize the efficacy of conventional chemo-/radiotherapy. Emerging interdisciplinary techniques including photodynamic, nanoparticle system, and Bio-Electro-Magnetic-Energy-Regulation (BEMER) therapy are promising measures to broaden the potency of ROS modulation for the benefit of chemo-/radiotherapy in head and neck cancer.

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Section: Exploit Novel Small Molecular Compounds Targeting Rosmentioning

confidence: 99%

ROS-Mediated Therapeutic Strategy in Chemo-/Radiotherapy of Head and Neck Cancer

Huang

Pan

2020

Oxidative Medicine and Cellular Longevity

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“…The lactate dehydrogenase level in red blood cells is ~100-times that in serum, and lactate dehydrogenase is also a “functional checkpoint” for anaerobic glycolysis of sugar and gluconeogenesis. 27 All of the patients who died in our study had multiple-organ dysfunction, and these changes led to increased lactate dehydrogenase levels.…”

Section: Discussionmentioning

confidence: 73%

Clinical Characteristics of Adult Hemophagocytic Lymphohistiocytosis in the Emergency Department

Zhang¹,

Huang²,

Li³

et al. 2021

IJGM

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Purpose To determine the clinical manifestations and results of adult hemophagocytic lymphohistiocytosis (HLH) patients in our emergency department. Methods We retrospectively evaluated patients with HLH from 1 April 2018 to 31 December 2020. The clinical data of these patients (basic information, symptoms, vital signs, laboratory results, HLH diagnostic criteria, H Score, main treatments, outcomes) were collected. Results Thirty-three patients (23 males and 10 females; 40.55±18.78 years) with 34 clinical episodes (one male had two clinical episodes and died during the second episode) were enrolled. Twenty-five patients were placed in a “survivor” group, and nine patients were categorized into a “deceased” group. Fever, splenomegaly, hemoglobin <90 g/L and platelet count <100×10 9 /L most commonly met the diagnostic standard for HLH. The H Score results in the survival group and deceased group was 212.4±37.18 and 252.1±40.95, respectively. Viral infection was the most common reason for HLH, followed by immune-system disease and cancer. Laboratory tests showed that deceased-group patients had multiple-organ dysfunction. Multivariate logistic regression showed that the lactate dehydrogenase (lactate dehydrogenase) level (P = 0.039; odds ratio, 0.999) was significantly related to death. Conclusion In the emergency department, HLH should be considered for critically ill patients with fever, splenomegaly, low hemoglobin and low platelet count. The H Score might be useful to diagnose HLH quickly. In our study, 26.47% of HLH patients died in the emergency department, and patients with a significantly increased lactate dehydrogenase level had a markedly increased risk of death.

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“…In addition, our present results showed that both initial LDH level on admission and peak LDH level during hospitalization were positively associated with the severe SARS-CoV-2 infection. LDH is a nonspecific enzyme found ubiquitously in cells [16]. Although the knowledge of the association between LDH and COVID-19 severity is limited, previous studies demonstrated strong evidence of an elevated risk for developing adverse outcomes or acute respiratory distress syndrome in SARS patients with elevated LDH [17,18].…”

Section: Discussionmentioning

confidence: 99%

Clinical features and laboratory findings of SARS-CoV-2 infection in hospitalized patients

Wang

Zhang

et al. 2020

Preprint

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Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a new emerging public health crisis to the world. However, data are still limited on the clinical features and laboratory findings in COVID-19 patients.Methods: Medical records including demographics characteristics, clinical features, laboratory findings and radiological materials of 66 hospitalized COVID-19 patients were collected between Jan 23 and Mar 9, 2020. Symptoms/signs with potential association with the disease severity were analyzed.Results: Of 66 hospitalized COVID-19 patients, the male-to-female ratio was 44:22. There were eight cases potentially exposed to one single patient. The most common initial symptoms of SARS-CoV-2 infection were fever (77.3%) and cough (74.2%). Compared to those with non-severe infection, the severe patients were more likely to be older (62.6 ± 15.1 vs 46.9 ± 13.3 years. P = 0.001) and with more infected lobes. As the results shown, higher initial (on admission) and peak (during hospitalization) counts of lymphocyte were inversely associated with the severe SARS-CoV-2 infection (both OR: 0.01 every 1´109/L decrease). However, the elevated initial neutrophil counts (OR: 1.63 every 1´109/L increase), initial and peak levels of LDH (OR: 1.02 and 1.01 every 1 U/L increase), peak levels of CRP (OR: 1.03 every 1 mg/L increase), AST (OR: 1.06 every 1 U/L increase) and ALT (OR: 1.02 every 1 U/L increase) were significantly associated with COVID-19 severity.Conclusion: Our present study indicated that fever and cough were the most common initial symptoms of SARS-CoV-2 infection, and the virus could be efficiently spread by person-to-person transmission. In addition, lymphocyte and neutrophil counts, and serum levels of AST, ALT, CRP and LDH should be useful for the evaluation on COVID-19 severity.

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Lactate Dehydrogenase Inhibition: Biochemical Relevance and Therapeutical Potential

Cited by 36 publications

References 69 publications

ROS-Mediated Therapeutic Strategy in Chemo-/Radiotherapy of Head and Neck Cancer

ROS-Mediated Therapeutic Strategy in Chemo-/Radiotherapy of Head and Neck Cancer

Clinical Characteristics of Adult Hemophagocytic Lymphohistiocytosis in the Emergency Department

Clinical features and laboratory findings of SARS-CoV-2 infection in hospitalized patients

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