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American Family Physician Dec 2004Genital warts caused by human papillomavirus infection are encountered commonly in primary care. Evidence guiding treatment selection is limited, but treatment... (Review)
Review
Genital warts caused by human papillomavirus infection are encountered commonly in primary care. Evidence guiding treatment selection is limited, but treatment guidelines recently have changed. Biopsy, viral typing, acetowhite staining, and other diagnostic measures are not routinely required. The goal of treatment is clearance of visible warts; some evidence exists that treatment reduces infectivity, but there is no evidence that treatment reduces the incidence of cervical and genital cancer. The choice of therapy is based on the number, size, site, and morphology of lesions, as well as patient preferences, cost, convenience, adverse effects, and clinician experience. Patient-applied therapy such as imiquimod cream or podofilox is increasingly recommended. Podofilox, imiquimod, surgical excision, and cryotherapy are the most convenient and effective options. Fluorouracil and interferon are no longer recommended for routine use. The cost per successful treatment course is approximately dollars 200 to dollars 300 for podofilox, cryotherapy, electrodesiccation, surgical excision, laser treatment, and the loop electrosurgical excision procedure.
Topics: Algorithms; Aminoquinolines; Condylomata Acuminata; Cryotherapy; Decision Trees; Diagnosis, Differential; Electrosurgery; Evidence-Based Medicine; Family Practice; Female; Genital Diseases, Female; Genital Diseases, Male; Humans; Imiquimod; Keratolytic Agents; Laser Therapy; Male; Patient Selection; Podophyllotoxin; Practice Guidelines as Topic; Primary Health Care; Treatment Outcome
PubMed: 15617297
DOI: No ID Found -
Biomolecules Apr 2021Podophyllotoxin, along with its various derivatives and congeners are widely recognized as broad-spectrum pharmacologically active compounds. Etoposide, for instance, is... (Review)
Review
Podophyllotoxin, along with its various derivatives and congeners are widely recognized as broad-spectrum pharmacologically active compounds. Etoposide, for instance, is the frontline chemotherapeutic drug used against various cancers due to its superior anticancer activity. It has recently been redeveloped for the purpose of treating cytokine storm in COVID-19 patients. Podophyllotoxin and its naturally occurring congeners have low bioavailability and almost all these initially discovered compounds cause systemic toxicity and development of drug resistance. Moreover, the production of synthetic derivatives that could suffice for the clinical limitations of these naturally occurring compounds is not economically feasible. These challenges demanded continuous devotions towards improving the druggability of these drugs and continue to seek structure-optimization strategies. The discovery of renewable sources including microbial origin for podophyllotoxin is another possible approach. This review focuses on the exigency of innovation and research required in the global R&D and pharmaceutical industry for podophyllotoxin and related compounds based on recent scientific findings and market predictions.
Topics: Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Antineoplastic Agents, Phytogenic; Cytokine Release Syndrome; Drug Discovery; Drug Repositioning; Humans; Neoplasms; Podophyllotoxin; Podophyllum; COVID-19 Drug Treatment
PubMed: 33921719
DOI: 10.3390/biom11040603 -
Molecules (Basel, Switzerland) Dec 2022Plants containing podophyllotoxin and its analogues have been used as folk medicines for centuries. The characteristic chemical structures and strong biological... (Review)
Review
Plants containing podophyllotoxin and its analogues have been used as folk medicines for centuries. The characteristic chemical structures and strong biological activities of this class of compounds attracted attention worldwide. Currently, more than ninety natural podophyllotoxins were isolated, and structure modifications of these molecules were performed to afford a variety of derivatives, which offered optimized anti-tumor activity. This review summarized up to date reports on natural occurring podophyllotoxins and their sources, structural modification and biological activities. Special attention was paid to both structural modification and optimized antitumor activity. It was noteworthy that etoposide, a derivative of podophyllotoxin, could prevent cytokine storm caused by the recent SARS-CoV-2 viral infection.
Topics: Humans; Podophyllotoxin; Antineoplastic Agents, Phytogenic; Structure-Activity Relationship; COVID-19; SARS-CoV-2
PubMed: 36615496
DOI: 10.3390/molecules28010302 -
Viruses Oct 2016Human cytomegalovirus is a ubiquitous β-herpesvirus that infects many different cell types through an initial binding to cell surface receptors followed by a fusion...
Human cytomegalovirus is a ubiquitous β-herpesvirus that infects many different cell types through an initial binding to cell surface receptors followed by a fusion event at the cell membrane or endocytic vesicle. A recent high-throughput screen to identify compounds that block a step prior to viral gene expression identified podofilox as a potent and nontoxic inhibitor. Time-of-addition studies in combination with quantitative-PCR analysis demonstrated that podofilox limits an early step of virus entry at the cell surface. Podofilox was also able to drastically reduce infection by herpes simplex 1, an α-herpesvirus with a very similar entry process to CMV. Podofilox caused a reduced maximal plateau inhibition of infection by viruses with single step binding processes prior to fusion-like Newcastle disease virus, Sendai virus, and influenza A virus or viruses that enter via endocytosis like vesicular stomatitis virus and a clinical-like strain of CMV. These results indicate that microtubules appear to be participating in the post-binding step of virus entry including the pre- and post-penetration events. Modulation of the plasma membrane is required to promote virus entry for herpesviruses, and that podofilox, unlike colchicine or nocodazole, is able to preferentially target microtubule networks at the plasma membrane.
Topics: Antiviral Agents; Cell Line; Cytomegalovirus; Herpesvirus 1, Human; Humans; Podophyllotoxin; RNA Viruses; Tubulin Modulators; Virus Internalization
PubMed: 27783035
DOI: 10.3390/v8100295 -
Molecules (Basel, Switzerland) Jan 2020Lignans are widely produced by various plant species; they are a class of natural products that share structural similarity. They usually contain a core scaffold that is... (Review)
Review
Lignans are widely produced by various plant species; they are a class of natural products that share structural similarity. They usually contain a core scaffold that is formed by two or more phenylpropanoid units. Lignans possess diverse pharmacological properties, including their antiviral activities that have been reported in recent years. This review discusses the distribution of lignans in nature according to their structural classification, and it provides a comprehensive summary of their antiviral activities. Among them, two types of antiviral lignans-podophyllotoxin and bicyclol, which are used to treat venereal warts and chronic hepatitis B (CHB) in clinical, serve as examples of using lignans for antivirals-are discussed in some detail. Prospects of lignans in antiviral drug discovery are also discussed.
Topics: Antiviral Agents; Benzodioxoles; Biological Products; Biphenyl Compounds; Drug Development; Furans; Lignans; Masoprocol; Plants; Podophyllotoxin
PubMed: 31906391
DOI: 10.3390/molecules25010183 -
The New England Journal of Medicine Aug 1985
Topics: Brain Neoplasms; Etoposide; Female; Humans; Podophyllotoxin; Pregnancy; Trophoblastic Neoplasms; Uterine Neoplasms
PubMed: 2991763
DOI: 10.1056/NEJM198508223130815 -
Advances in Health Sciences Education :... Dec 2022Professionals will increasingly be confronted with new insights and changes. This raises questions as to what kind of expertise professionals need, and how development... (Review)
Review
Professionals will increasingly be confronted with new insights and changes. This raises questions as to what kind of expertise professionals need, and how development of this expertise can be influenced within the contexts of both education and work. The terms adaptive expertise and adaptive performance are well-known concepts in the domains of education and Human Resource Development respectively. The literature, however, lacks a conceptual overview. Our research seeks to provide an overview on how adaptive expertise and adaptive performance are conceptualized. In addition we looked for what individual, task and organizational characteristics relate to adaptive expertise. We mined information drawn from existing reviews in an overview of reviews. Nine reviews met the inclusion criteria. Adaptive performance is best referred to as the visible expression of an adaptive expert and this is triggered by 'change'. The scope of this 'change' lies somewhere between change that is 'new for the learner' and change that is 'new for everyone in the whole world'. The extent to and way in which a learner or professional is able to deal with this change depends on the maturity of the learner or professional. We found numerous individual, task and environmental characteristics related to adaptive expertise and adaptive performance. The nature and relation of these characteristics, and their specificity in relation to adaptive expertise and adaptive performance are visualized in a figure, but also provide several suggestions for future research.
Topics: Humans; Educational Status; Workplace; Clinical Competence; Etoposide; Ifosfamide
PubMed: 36508136
DOI: 10.1007/s10459-022-10190-y -
International Journal of Molecular... Jun 2021Polyphenols are naturally occurring compounds found in abundance in fruits and vegetables. Their health-promoting properties and their use in the prevention and... (Review)
Review
Polyphenols are naturally occurring compounds found in abundance in fruits and vegetables. Their health-promoting properties and their use in the prevention and treatment of many human diseases, including cancer, have been known for years. Many anti-cancer drugs are derived from these natural compounds. Etoposide, which is a semi-synthetic derivative of podophyllotoxin, a non-alkaloid lignan isolated from the dried roots and rhizomes of or (Berberidaceae), is an example of such a compound. In this review, we present data on the effects of polyphenols on the anti-cancer activity of etoposide in in vitro and in vivo studies.
Topics: Animals; Antineoplastic Agents, Phytogenic; Biomarkers; Cell Line, Tumor; Cell Proliferation; Cell Survival; Disease Models, Animal; Drug Synergism; Etoposide; Humans; Neoplasms; Polyphenols; Structure-Activity Relationship; Topoisomerase II Inhibitors; Xenograft Model Antitumor Assays
PubMed: 34202987
DOI: 10.3390/ijms22126602 -
Autophagy Aug 2021Induction of macroautophagy (hereafter termed autophagy) is a strategy to improve the outcome of antineoplastic therapies by facilitating the induction of immunogenic... (Review)
Review
Induction of macroautophagy (hereafter termed autophagy) is a strategy to improve the outcome of antineoplastic therapies by facilitating the induction of immunogenic cancer cell death and the consequent immune recognition of malignant cells. We analyzed 65,000 distinct compounds by means of a phenotypic discovery platform for autophagy induction and identified the IGF1R (insulin like growth factor 1 receptor) inhibitor picropodophyllin (PPP) as a potent inducer of autophagic flux. We found that PPP acts on-target, as an inhibitor of the tyrosine kinase activity of IGF1R and enhances the release of adenosine triphosphate, ATP, from stressed and dying cancer cells in vitro, thereby improving the therapeutic efficacy of chemoimmunotherapy in cancer-bearing mice. This PPP effect was phenocopied by another IGF1R inhibitor, linsitinib. Moreover, in human triple-negative breast cancer, phosphorylation of IGF1R correlates with reduced autophagy, an unfavorable local immune profile and poor prognosis. In summary, IGF1R inhibition may constitute a novel strategy for the treatment of cancer in the context of chemoimmunotherapy.
Topics: Animals; Autophagy; Cell Proliferation; Humans; Imidazoles; Podophyllotoxin; Protein Kinase Inhibitors; Pyrazines; Receptor, IGF Type 1
PubMed: 34110249
DOI: 10.1080/15548627.2021.1936934 -
Journal of Thoracic Oncology : Official... Sep 2022In the phase 1/3 IMpower133 study, atezolizumab plus carboplatin and etoposide (CP/ET) followed by maintenance atezolizumab for first-line treatment of extensive-stage... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
In the phase 1/3 IMpower133 study, atezolizumab plus carboplatin and etoposide (CP/ET) followed by maintenance atezolizumab for first-line treatment of extensive-stage SCLC (ES-SCLC) led to improvement in both overall survival (OS) and progression-free survival (PFS) versus placebo plus CP/ET followed by maintenance placebo. We explored the benefit of atezolizumab versus placebo in the subset of patients who reached the IMpower133 maintenance phase and the safety profile of maintenance therapy.
METHODS
Patients with untreated ES-SCLC were randomized 1:1 to four 21-day cycles of CP/ET with atezolizumab or placebo, followed by maintenance atezolizumab or placebo. The primary end points were OS and investigator-assessed PFS. A multivariate Cox model from the start of maintenance treatment was used to evaluate the treatment effect and account for lead-time bias; a generalized linear model was used to identify prognostic or predictive characteristics for reaching the maintenance phase.
RESULTS
A similar proportion of patients in each arm received at least the first dose of maintenance therapy (atezolizumab: 77%, n = 154 of 201; placebo: 81%, n = 164 of 202) and were included in the maintenance analysis population. An Eastern Cooperative Oncology Group performance status of 0 and absence of liver metastases at baseline were identified as prognostic factors for reaching the maintenance phase. The positive treatment effect with atezolizumab remained after adjusting for baseline characteristics. Median OS and PFS from the start of maintenance therapy in the atezolizumab versus placebo arm were 12.5 versus 8.4 months (hazard ratio = 0.59, 95% confidence interval: 0.43-0.80) and 2.6 versus 1.8 months (hazard ratio = 0.63 [95% confidence interval: 0.49-0.80]), respectively. Treatment-related adverse events from the start of maintenance therapy occurred in 41% (n = 64 of 155) and 25% (n = 41 of 163) of safety-evaluable patients in the atezolizumab and placebo arms, respectively, and were grade 3 or 4 in 28% (n = 43 of 155) and 23% (n = 37 of 163) of the respective populations; no patient in the atezolizumab arm and one patient in the placebo arm had a grade 5 treatment-related adverse event.
CONCLUSIONS
These data in the context of other immunotherapy trials in ES-SCLC suggest that induction with atezolizumab plus CP/ET and maintenance treatment with atezolizumab are important components that contributed to the OS benefit observed in IMpower133. Safety results from randomization and from the start of maintenance therapy were similar between the treatment arms despite the continuation of atezolizumab in the maintenance phase.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Etoposide; Humans; Lung Neoplasms; Small Cell Lung Carcinoma
PubMed: 35764236
DOI: 10.1016/j.jtho.2022.05.016