RESUMO
Lung cancer stands as one of the most lethal diseases and is the foremost cause of cancer-related mortalities worldwide. The pathophysiology of lung cancer is multifaceted, and it includes multiple cell signaling pathways and other complex factors such as oxidative stress and genetics. The association of HPV with lung carcinogenesis was first proposed in 1979, and since then, scientists worldwide have been putting forward several hypotheses to establish a relationship between this virus and lung cancer. Although studies have reported the presence of HPV in lung cancer, the exact mechanism of entry and the route of transmission have not been elucidated clearly till date. Numerous studies across the globe have detected differentially expressed HPV oncoproteins in lung cancer patients and found their association with the critical cell signaling pathways that leads to the development and progression of lung cancer. Many reports have also provided evidence stating the involvement of HPV in determining the survival status of lung cancer patients. The present review recapitulates the studies evincing the association of HPV and lung cancer, its route of transmission and mechanism of action; the detection of the virus and treatment opportunities for HPV-positive lung cancer; and the severity associated with this disease. Therefore, this will provide an explicit idea and would help to develop preventive measures and specific as well as effective treatment for HPV-associated lung carcinogenesis.
Assuntos
Neoplasias Pulmonares , Papillomaviridae , Infecções por Papillomavirus , Humanos , Neoplasias Pulmonares/virologia , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/complicações , Papillomaviridae/patogenicidade , Carcinogênese , Papillomavirus HumanoRESUMO
The continuous pursuit of designing an ideal infection imaging agent is a crucial and ongoing endeavor in the field of biomedical research. Duramycin, an antimicrobial peptide exerts its antimicrobial action on bacteria by specific recognition of phosphatidylethanolamine (PE) moiety present on most bacterial membranes, particularly Escherichia coli (E. coli). E. coli membranes contain more than 60% PE. Therefore, duramycin is an attractive candidate for the formulation of probes for in situ visualization of E. coli driven focal infections. The aim of the present study is to develop 99m Tc labeled duramycin as a single-photon emission computed tomography (SPECT)-based agent to image such infections. Duramycin was successfully conjugated with a bifunctional chelator, hydrazinonicotinamide (HYNIC). PE specificity of HYNIC-duramycin was confirmed by a dye release assay on PE-containing model membranes. Radiolabeling of HYNIC-duramycin with 99m Tc was performed with consistently high radiochemical yield (>90%) and radiochemical purity (>90%). [99m Tc]Tc-HYNIC-duramycin retained its specificity for E. coli, in vitro. SPECT and biodistribution studies showed that the tracer could specifically identify E. coli driven infection at 3 h post injection. While 99m Tc-labeled duramycin is employed for monitoring early response to cancer therapy and cardiotoxicity, the current studies have confirmed, for the first time, the potential of utilizing 99m Tc labeled duramycin as an imaging agent for detecting bacteria. Its application in imaging PE-positive bacteria represents a novel and promising advancement.
Assuntos
Bacteriocinas , Escherichia coli , Compostos de Organotecnécio , Compostos de Organotecnécio/química , Distribuição Tecidual , Peptídeos/química , Peptídeos/metabolismoRESUMO
Oral cancer is one of the leading causes of cancer-related deaths, and it has become a matter of serious concern due to the alarming rise in its incidence rate worldwide. Despite recent advancements in oral cancer treatment strategies, there are no significant improvements in patient's survival rate. Among the numerous cell signaling pathways involved in oral cancer development and progression, STAT3 is known to play a multifaceted oncogenic role in shaping the tumor pathophysiology. STAT3 hyperactivation in oral cancer contributes to survival, proliferation, invasion, epithelial to mesenchymal transition, metastasis, immunosuppression, chemoresistance, and poor prognosis. A plethora of pre-clinical and clinical studies have documented the role of STAT3 in the initiation and development of oral cancer and showed that STAT3 inhibition holds significant potential in the prevention and treatment of this cancer. However, to date, targeting STAT3 activation mainly involves inhibiting the upstream signaling molecules such as JAK and IL-6 receptors. The major challenge in targeting STAT3 lies in the complexity of its phosphorylation- and dimerization-independent functions, which are not affected by disrupting the upstream regulators. The present review delineates the significance of the STAT3 pathway in regulating various hallmarks of oral cancer. In addition, it highlights the STAT3 inhibitors identified to date through various preclinical and clinical studies that can be employed for the therapeutic intervention in oral cancer treatment.
Assuntos
Transição Epitelial-Mesenquimal , Neoplasias Bucais , Linhagem Celular Tumoral , Proliferação de Células , Transição Epitelial-Mesenquimal/fisiologia , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Bucais/tratamento farmacológico , Fosforilação , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/fisiologiaRESUMO
Ovarian cancer is one of the deadliest gynecological cancers and the 7th most commonly occurring cancer in women globally. The 5 year survival rate is estimated to be less than 25 %, as in most cases, diagnosis occurs at an advanced stage. Despite recent advancements in treatment, clinical outcomes still remain poor, thus implicating the need for urgent identification of novel therapeutics for the treatment of this cancer. Ovarian cancer is considered a low immune reactive cancer as the tumor cells express insufficient neoantigens to be recognized by the immune cells and thus tend to escape from immune surveillance. Thus, in the recent decade, immunotherapy has gained significant attention and has rejuvenated the understanding of immune regulation in tumor biology. One of the critical immune checkpoints is programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis. Engagement of PD-1 to PD-L1 promotes immunologic tolerance and suppresses the effector T cells and maintains tumor Tregs, thus playing a crucial role in enhancing tumor survival. Recent studies are targeted to develop inhibitors that block this signal to augment the anti-tumor activity of immune cells. Also, compared to monotherapy, the combinatorial treatment of immune checkpoint inhibitors with small molecule inhibitors have shown promising results with improved efficacy and acceptable adverse events. The present review provides an overview of the PD-1/PD-L1 axis and role of non-coding RNAs in regulating this axis. Moreover, we have highlighted the various preclinical and clinical investigations on PD-1/PD-L1 immune checkpoint inhibitors and have discussed the limitations of immunotherapies in ovarian cancer.
Assuntos
Antígeno B7-H1 , Neoplasias Ovarianas , Antígeno B7-H1/metabolismo , Carcinoma Epitelial do Ovário/tratamento farmacológico , Feminino , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Neoplasias Ovarianas/tratamento farmacológico , Receptor de Morte Celular Programada 1/metabolismoRESUMO
Chronic diseases are considered a major public health concern worldwide, and most of these diseases like cancer, cardiovascular, metabolic, and neurological disorders occur due to atypical regulation of multiple signaling pathways. It has also been observed that most of the currently approved therapies for these diseases fail to show prolonged efficacy due to their mono-targeted nature and are associated with the development of chemoresistance, thus restricting their utility. The plant-derived compounds, on the other hand, show multi-targeted nature, and thus these phytochemicals have gained wide attention as they offer negligible side effects. The present review aims to recapitulate the potential effects of one such phytochemical, Scopoletin, which was found to have a diverse range of pharmacological activities such as anti-cancer, anti-diabetic, anti-inflammatory, cardioprotective, hepatoprotective, etc. Scopoletin modulated multiple molecular signatures in cancer, including AMPK, EGFR, MAPK/ ERK, NF-κB, PI3K/Akt/ mTOR, and STAT3; regulated the levels of critical markers of metabolic diseases such as ALT, AST, TG, and TC; inflammatory diseases such as ILs and TNFs; neurological diseases such as AChE, etc. thus relieving the symptoms and severity associated with these diseases. Further, this compound has a non-toxic nature and possesses an excellent pharmacokinetic property, which warrants further investigation in clinical settings for developing it as a potential drug.
Assuntos
Neoplasias , Escopoletina , Anti-Inflamatórios/uso terapêutico , Doença Crônica , Humanos , NF-kappa B/metabolismo , Neoplasias/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Compostos Fitoquímicos/farmacologia , Escopoletina/farmacologia , Escopoletina/uso terapêutico , Transdução de SinaisRESUMO
The medicinal plant Scutellaria baicalensis, commonly known as Chinese skullcap or Huang-Qin, has been used as a traditional medicine for several thousand years. The roots of this plant contain bioactive compounds, such as wogonin (WOG), wogonoside, baicalein, and baicalin. The aim of this article is to evaluate the therapeutic potential and mechanisms of action of WOG against different cancers. Numerous in vitro and in vivo studies have revealed that WOG exerts immense therapeutic potential against bladder cancer, breast cancer, cholangiocarcinoma, cervical cancer, colorectal cancer, gallbladder cancer, gastric cancer, glioblastoma, head and neck cancer, hepatic cancer, leukemia, lung cancer, lymphoma, melanoma, multiple myeloma, neuroblastoma, osteosarcoma, ovarian cancer, pancreatic cancer, prostate cancer, and renal cancer by regulating various cell signaling pathways. WOG, in combination with established chemotherapeutic drugs, improves the efficacy of treatment and lowers toxicity. Nevertheless, human trials are warranted to validate these findings. Numerous preclinical studies, combined with an extensive margin of safety and no severe side effects, underscore WOG's therapeutic potential as an anticancer drug. These studies propound the use of WOG as a potential anticancer candidate; however, further high-quality studies are required to firmly establish the clinical efficacy of WOG for the prevention and treatment of human malignancies.
Assuntos
Medicamentos de Ervas Chinesas , Flavanonas , Neoplasias , Scutellaria , Medicamentos de Ervas Chinesas/farmacologia , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Flavonoides , Humanos , Masculino , Neoplasias/tratamento farmacológico , Neoplasias/prevenção & controle , Extratos Vegetais/farmacologia , Scutellaria baicalensisRESUMO
Despite significant advancements made in the treatment of cancer during the past several decades, it remains one of the leading causes of death worldwide killing approximately 9.6 million people annually. The major challenge for therapeutic success is the development of chemoresistance in cancer cells against conventional chemotherapeutic agents via modulation of numerous survival and oncogenic signaling pathways. Therefore, sensitization of cancer cells to conventional drugs using multitargeted agents that suppress the survival and oncogenic pathways, in single or in combination, is an emerging strategy to overcome drug-resistance. During the last couple of decades, phytochemicals such as curcumin, resveratrol, tocotrienol and quercetin have emerged as potential chemosensitizing agents in cancer cells due to their less toxic and multitargeted properties. Numerous preclinical and clinical studies enumerated their potential to prevent drug resistance and sensitize cancer cells to chemotherapeutic agents by modulating several genes/proteins or pathways that regulate the key factors during the growth and progression of tumors such as inhibition of anti-apoptotic proteins, activation of pro-apoptotic proteins, reduced expression of different transcription factors, chemokines, enzymes, cell adhesion molecules, protein tyrosine kinases and cell cycle regulators. Therefore, natural chemosensitizing agents will have a special place in cancer treatment in the near future. This comprehensive review summarizes data obtained from various in vitro, in vivo and clinical studies to provide a new perspective for the application of agents obtained from "Mother Nature" as potential chemosensitizers for further cancer drug research and development.
Assuntos
Antineoplásicos , Curcumina , Neoplasias , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Curcumina/farmacologia , Curcumina/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Transdução de SinaisRESUMO
Gall bladder cancer (GBC) is a rare and one of the most aggressive types of malignancies, often associated with a poor prognosis and survival. It is a highly metastatic cancer and is often not diagnosed at the initial stages, which contributes to a poor survival rate of patients. The poor diagnosis and chemoresistance associated with the disease limit the scope of the currently available surgical and nonsurgical treatment modalities. Thus, there is a need to explore novel therapeutic targets and biomarkers that will help relieve the severity of the disease and lead to advanced therapeutic strategies. Accumulating evidence has correlated the atypical expression of various noncoding RNAs (ncRNAs), including circular RNAs (circRNAs), long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and small nucleolar RNAs (snoRNA) with the increased cell proliferation, epithelial-mesenchymal transition (EMT), invasion, migration, metastasis, chemoresistance, and decreased apoptosis in GBC. Numerous reports have indicated that the dysregulated expression of ncRNAs is associated with poor prognosis and lower disease-free and overall survival in GBC patients. These reports suggest that ncRNAs might be considered novel diagnostic and prognostic markers for the management of GBC. The present review recapitulates the association of various ncRNAs in the initiation and progression of GBC and the development of novel therapeutic strategies by exploring their functional and regulatory role.
Assuntos
Resistencia a Medicamentos Antineoplásicos , Neoplasias da Vesícula Biliar/genética , RNA não Traduzido/genética , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Neoplasias da Vesícula Biliar/mortalidade , Regulação Neoplásica da Expressão Gênica , Humanos , Prognóstico , Análise de SobrevidaRESUMO
In recent years, triple-negative breast cancer (TNBC) has emerged as the most aggressive subtype of breast cancer and is usually associated with increased mortality worldwide. The severity of TNBC is primarily observed in younger women, with cases ranging from approximately 12%-24% of all breast cancer cases. The existing hormonal therapies offer limited clinical solutions in completely circumventing the TNBC, with chemoresistance and tumor recurrences being the common hurdles in the path of TNBC treatment. Accumulating evidence has correlated the dysregulation of long noncoding RNAs (lncRNAs) with increased cell proliferation, invasion, migration, tumor growth, chemoresistance, and decreased apoptosis in TNBC. Various clinical studies have revealed that aberrant expression of lncRNAs in TNBC tissues is associated with poor prognosis, lower overall survival, and disease-free survival. Due to these specific characteristics, lncRNAs have emerged as novel diagnostic and prognostic biomarkers for TNBC treatment. However, the underlying mechanism through which lncRNAs perform their actions remains unclear, and extensive research is being carried out to reveal it. Therefore, understanding of mechanisms regulating the modulation of lncRNAs will be a substantial breakthrough in effective treatment therapies for TNBC. This review highlights the association of several lncRNAs in TNBC progression and treatment, along with their possible functions and mechanisms.
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Carcinogênese/genética , Recidiva Local de Neoplasia/genética , RNA Longo não Codificante/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , RNA Longo não Codificante/genéticaRESUMO
Oral cancer (OC) is a devastating disease that takes the lives of lots of people globally every year. The current spectrum of treatment modalities does not meet the needs of the patients. The disease heterogeneity demands personalized medicine or targeted therapies. Therefore, there is an urgent need to identify potential targets for the treatment of OC. Abundant evidence has suggested that the components of the protein kinase B (AKT)/ mammalian target of rapamycin (mTOR) pathway are intrinsic factors for carcinogenesis. The AKT protein is central to the proliferation and survival of normal and cancer cells, and its downstream protein, mTOR, also plays an indispensable role in the cellular processes. The wide involvement of the AKT/mTOR pathway has been noted in oral squamous cell carcinoma (OSCC). This axis significantly regulates the various hallmarks of cancer, like proliferation, survival, angiogenesis, invasion, metastasis, autophagy, and epithelial-to-mesenchymal transition (EMT). Activated AKT/mTOR signaling is also associated with circadian signaling, chemoresistance and radio-resistance in OC cells. Several miRNAs, circRNAs and lncRNAs also modulate this pathway. The association of this axis with the process of tumorigenesis has culminated in the identification of its specific inhibitors for the prevention and treatment of OC. In this review, we discussed the significance of AKT/mTOR signaling in OC and its potential as a therapeutic target for the management of OC. This article also provided an update on several AKT/mTOR inhibitors that emerged as promising candidates for therapeutic interventions against OC/head and neck cancer (HNC) in clinical studies.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Bucais/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/metabolismo , Ensaios Clínicos como Assunto , Humanos , Neoplasias Bucais/metabolismo , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais/efeitos dos fármacosRESUMO
Background According to GLOBOCAN 2018, oral cancer was reported as the second highest cancer prevalent in India. Despite the several therapies available for oral cancer treatment, tumor recurrence and distant metastasis persist. This study investigates the anticancer potential of Persicaria odorata, commonly known as Vietnamese coriander, used widely in traditional systems of medicine for the treatment of inflammation, stomach ailments, tumors, etc. Methods The crude methanolic extract of P. odorata (MPo) was prepared. The anticancer properties of MPo on SAS cells and other human oral squamous cell carcinoma cell line were evaluated using in vitro experimental conditions. The phytochemical constituents present in the MPo were also determined. Results Persicaria odorata possesses antiproliferative, antisurvival, antimetastatic activities, and induced cell cycle arrest in the G2 phase. It inhibited Akt-mammalian target of rapamycin (mTOR) signaling pathway and also downregulated the expression of essential proteins that are involved in tumorigenesis such as cyclin D1, cyclooxygenase 2 (COX2), survivin, matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor-A (VEGF-A). Moreover, the presence of flavonoids and quinones also revealed the anticancer activity of the plant. Conclusion Overall, our study concludes that P. odorata exhibits its anticancer properties through the downregulation of Akt/mTOR signaling pathway in a dose-dependent manner.
Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Coriandrum/química , Neoplasias Bucais/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Fase G2/efeitos dos fármacos , Humanos , Índia , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , VietnãRESUMO
Tumor necrosis factor (TNF)-α, the most potent proinflammatory cytokine discovered to date, was first isolated in 1984 from human macrophage cells. Initially, it was thought to be a protein that was cytotoxic to tumor cells. But later, it was regarded as an agent that promotes inflammation and other chronic diseases found in humans. Currently, we know that the TNF superfamily (TNFS) has 19 members that perform a wide variety of functions via > 40 TNF receptors. Of TNFS members, TNF-α has been studied extensively and was found to be implicated in numerous autoimmune diseases, such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriasis, systemic lupus erythematosus, juvenile idiopathic arthritis, and diabetes. Thus, agents that can inhibit TNF-α have great potential for prevention and treatment of chronic diseases. To date, the U.S. Food and Drug Administration has approved many TNF-α blockers, such as etanercept, infliximab, adalimumab, certolizumab pegol, and golimumab. These agents can block TNF-α actions and be used to treat different diseases. However, the uses of TNF-α blockers are not without serious adverse effects. Therefore, natural TNF-α blockers are best for developing safe, efficacious, and affordable agents for prevention and treatment of chronic diseases. The current review details the TNFS, functions of TNF-α in normal and disease conditions, roles of TNF-α blockers, and advantages and disadvantages.
Assuntos
Anti-Inflamatórios/uso terapêutico , Certolizumab Pegol/uso terapêutico , Etanercepte/uso terapêutico , Doenças do Sistema Imunitário/terapia , Inflamação/terapia , Receptores do Fator de Necrose Tumoral/imunologia , Fator de Necrose Tumoral alfa/imunologia , Animais , Anticorpos Monoclonais/uso terapêutico , Humanos , Doenças do Sistema Imunitário/imunologia , Inflamação/imunologia , Receptores do Fator de Necrose Tumoral/antagonistas & inibidores , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
Classical swine fever virus (CSFV) is the causative agent of a highly contagious disease in swine. The disease is endemic in different parts of the world and vaccination is the only way to protect pigs from CSFV infection. The virus surface protein E2 is the major immunogenic protein eliciting protective immunity against CSFV infection in swine. The whole virus antigen cannot differentiate CSFV from other pestiviruses as it cross reacts with border disease and bovine viral diarrhoea viruses. Commercial available ELISA is based on the whole CSFV particle and can lead to false positive results. Moreover, the available commercial ELISA is not cost effective. In the present study, a recombinant E2 protein based single serum dilution ELISA was developed which showed enhanced sensitivity, specificity and accuracy as compared to commercial CSFV detection ELISA. The recombinant E2 protein based ELISA could be an alternate to existing diagnostics against CSFV infection in pigs.
Assuntos
Anticorpos Antivirais/análise , Ensaio de Imunoadsorção Enzimática/veterinária , Proteínas do Envelope Viral/imunologia , Animais , Linhagem Celular , Ensaio de Imunoadsorção Enzimática/métodos , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Suínos , Proteínas do Envelope Viral/biossíntese , Proteínas do Envelope Viral/genéticaRESUMO
Classical swine fever virus (CSFV) is the causative agent of a highly contagious disease, hog cholera in pigs. The disease is endemic in many parts of the world, and vaccination is the only way to protect the animals from CSFV infection. The lapinized vaccine strains are occasionally not protective because of animal to animal passage, inadequate vaccination strategy, suboptimal vaccine dose, and emergence of new variants. The surface glycoprotein E2 of CSFV is a major antigenic determinant and can modulate the disease outcome in pigs. In the present study, we characterized the CSFV in porcine kidney cells. The CSFV vaccine strains showed enhanced replication following 15 passages in porcine kidney cells. Nucleotide sequence analysis of the E2 protein gene of the cell culture-adapted vaccine strain of CSFV showed a mutation in putative amino acid sequences that are identical to its virulent counterpart. The study suggests the possibility of exaltation in vaccine strains following its adaptation in host cells and paves the way for a further exploration of the biology of its outbreak.