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1.
J Mark Access Health Policy ; 12(3): 158-168, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39072307

RESUMO

Alopecia is an undesirable side effect of cancer chemotherapy. The mitigation of alopecia is a desirable adjunct treatment for patients with cancer. FDA-cleared scalp cooling (SC) devices have been successfully used to prevent or reduce chemotherapy-induced alopecia (CIA). This paper provides an understanding of the implementation and value of the new Insurance-Based Billing Model used in the USA for SC and its benefits compared with the original self-pay model. This improved compensation change will result in all patients in need, including underserved and disadvantaged populations, receiving equitable healthcare by allowing access to this valuable supportive care technology.

2.
Microorganisms ; 11(9)2023 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-37764007

RESUMO

Overuse of pesticides in agricultural soil and dye-polluted effluents severely contaminates the environment and is toxic to animals and humans making their removal from the environment essential. The present study aimed to assess the biodegradation of pesticides (cypermethrin (CYP) and imidacloprid (IMI)), and dyes (malachite green (MG) and Congo red (CR)) using biofilms of bacteria isolated from pesticide-contaminated soil and dye effluents. Biofilms of indigenous bacteria, i.e., Bacillus thuringiensis 2A (OP554568), Enterobacter hormaechei 4A (OP723332), Bacillus sp. 5A (OP586601), and Bacillus cereus 6B (OP586602) individually and in mixed culture were tested against CYP and IMI. Biofilms of indigenous bacteria i.e., Lysinibacillus sphaericus AF1 (OP589134), Bacillus sp. CF3 (OP589135) and Bacillus sp. DF4 (OP589136) individually and in mixed culture were tested for their ability to degrade dyes. The biofilm of a mixed culture of B. thuringiensis + Bacillus sp. (P7) showed 46.2% degradation of CYP compared to the biofilm of a mixed culture of B. thuringiensis + E. hormaechei + Bacillus sp. + B. cereus (P11), which showed significantly high degradation (70.0%) of IMI. Regarding dye biodegradation, a mixed culture biofilm of Bacillus sp. + Bacillus sp. (D6) showed 86.76% degradation of MG, which was significantly high compared to a mixed culture biofilm of L. sphaericus + Bacillus sp. (D4) that degraded only 30.78% of CR. UV-VIS spectroscopy revealed major peaks at 224 nm, 263 nm, 581 nm and 436 nm for CYP, IMI, MG and CR, respectively, which completely disappeared after treatment with bacterial biofilms. Fourier transform infrared (FTIR) analysis showed the appearance of new peaks in degraded metabolites and disappearance of a peak in the control spectrum after biofilm treatment. Thin layer chromatography (TLC) analysis also confirmed the degradation of CYP, IMI, MG and CR into several metabolites compared to the control. The present study demonstrates the biodegradation potential of biofilm-forming bacteria isolated from pesticide-polluted soil and dye effluents against pesticides and dyes. This is the first report demonstrating biofilm-mediated bio-degradation of CYP, IMI, MG and CR utilizing soil and effluent bacterial flora from Multan and Sheikhupura, Punjab, Pakistan.

4.
J Natl Cancer Inst ; 106(9)2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25190726

RESUMO

The number and diversity of cancer therapeutics in the pipeline has increased over the past decade due to an enhanced understanding of cancer biology and the identification of novel therapeutic targets. At the same time, the cost of bringing new drugs to market and the regulatory burdens associated with clinical drug development have progressively increased. The finite number of eligible patients and limited financial resources available to evaluate promising new therapeutics represent rate-limiting factors in the effort to translate preclinical discoveries into the next generation of standard therapeutic approaches. Optimal use of resources requires understanding and ultimately addressing inefficiencies in the cancer clinical trials system. Prior analyses have demonstrated that a large proportion of trials initiated by the National Cancer Institute (NCI) Cooperative Group system are never completed. While NCI Cooperative Group trials are important, they represent only a small proportion of all cancer clinical trials performed. Herein, we explore the problem of cancer clinical trials that fail to complete within the broader cancer clinical trials enterprise. Among 7776 phase II-III adult cancer clinical trials initiated between 2005-2011, we found a seven-year cumulative incidence of failure to complete of approximately 20% (95% confidence interval = 18% to 22%). Nearly 48000 patients were enrolled in trials that failed to complete. These trials likely contribute little to the scientific knowledge base, divert resources and patients from answering other critical questions, and represent a barrier to progress.


Assuntos
Antineoplásicos , Descoberta de Drogas , Término Precoce de Ensaios Clínicos/estatística & dados numéricos , Término Precoce de Ensaios Clínicos/tendências , Neoplasias/tratamento farmacológico , Adulto , Antineoplásicos/economia , Ensaios Clínicos como Assunto/estatística & dados numéricos , Ensaios Clínicos como Assunto/tendências , Descoberta de Drogas/economia , Humanos , National Cancer Institute (U.S.) , Sujeitos da Pesquisa , Estados Unidos/epidemiologia
5.
Cancer Treat Rev ; 40(5): 636-47, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24629273

RESUMO

BACKGROUND: The approach of combining cytotoxic chemotherapy with oral small molecule tyrosine kinase inhibitors (TKIs) has been explored in a large number of randomized trials, in a variety of tumor. We performed a systematic review and meta-analysis to evaluate the safety and efficacy of this therapeutic approach. PATIENTS AND METHODS: PubMed and the ASCO databases were searched up to March 2013. We included randomized trials in which the FDA approved vascular endothelial growth factor receptor (VEGFR) or epidermal growth factor receptor-family (EGFR)-targeted TKI in combination with chemotherapy was compared with chemotherapy alone in patients with any type of solid cancer. The endpoints included safety [fatal adverse events (FAEs), treatment discontinuation, any severe (grade 3 or 4) adverse events (AEs), and individual severe AEs] and efficacy [progression-free survival (PFS), and overall survival (OS)]. The pooled relative risk (RR) or hazard ratio (HR) were calculated. RESULTS: A total of 16,011 patients from 43 trials were included. Compared with chemotherapy alone, the addition of a TKI significantly increased the risk of FAEs (RR, 1.63; 95% CI, 1.32-2.01), treatment discontinuation (RR, 1.80; 95% CI, 1.58-2.06), and any severe AE (RR, 1.25; 95% CI, 1.16-1.36). The addition of a TKI was associated with a significant improvement in PFS (HR, 0.82; 95% CI, 0.76-0.89), but not OS (HR, 0.99; 95% CI, 0.95-1.03). CONCLUSIONS: It is important for physicians to weigh the risk of toxicity versus the modest PFS benefit associated with chemotherapy plus TKI in patients with solid cancers.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Receptores ErbB/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/efeitos dos fármacos , Administração Oral , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Relação Dose-Resposta a Droga , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Receptores ErbB/metabolismo , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Neoplasias/mortalidade , Neoplasias/patologia , Segurança do Paciente , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Medição de Risco , Resultado do Tratamento
6.
J Clin Oncol ; 32(2): 83-9, 2014 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-24323037

RESUMO

PURPOSE: Reporting adverse events is a critical element of a clinical trial publication. In 2003, the Consolidated Standards of Reporting Trials (CONSORT) group generated recommendations regarding the appropriate reporting of adverse events. The degree to which these recommendations are followed in oncology publications has not been comprehensively evaluated. METHODS: A review of citations from PubMed, Medline, and Embase published between Jan 1, 2009 and December 31, 2011, identified eligible randomized, controlled phase III trials in metastatic solid malignancies. Publications were assessed for 14 adverse event-reporting elements derived from the CONSORT harms extension statement; a completeness score (range, 0 to 14) was calculated by adding the number of elements reported. Linear regression analysis identified which publication characteristics associated with reporting completeness. RESULTS: A total of 175 publications, with data for 96,125 patients, were included in the analysis. The median completeness score was eight (range, three to 12). Most publications (96%) reported only adverse events occurring above a threshold rate or severity, 37% did not specify the criteria used to select which adverse events were reported, and 88% grouped together adverse events of varying severity. Regression analysis revealed that trials without a stated funding source and with an earlier year of publication had significantly lower completeness scores. CONCLUSION: Reporting of adverse events in oncology publications of randomized trials is suboptimal and characterized by substantial selectivity and heterogeneity. The development of oncology-specific standards for adverse event reporting should be established to ensure consistency and provide critical information required for medical decision-making.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/normas , Ensaios Clínicos Fase III como Assunto/normas , Publicações/normas , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Humanos , Modelos Lineares , Neoplasias/tratamento farmacológico , Relatório de Pesquisa/normas
7.
Crit Rev Oncol Hematol ; 88(1): 30-41, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23830806

RESUMO

We performed a systematic review and meta-analysis of hematologic toxicities associated with everolimus, an oral mammalian target of rapamycin (mTOR) inhibitor. Eligible studies included phase II and III trials of patients with solid tumors on 10mg of everolimus daily describing events of neutropenia, thrombocytopenia, anemia or lymphopenia. The incidence of everolimus-associated all-grade and high-grade (Grade 3-4) hematologic toxicities were, respectively: neutropenia: 21.7% and 3.6%; thrombocytopenia: 36.0% and 4.7%; anemia: 61.2% and 8.4% and lymphopenia: 40.9% and 14.9%. Everolimus was associated with an increased risk of all-grade neutropenia (RR=2.24, [95% CI 1.51-3.32]), all-grade (RR=9.19, [95% CI 4.51-18.70]) and high-grade (RR=7.46, [95% CI 2.58-21.61]) thrombocytopenia, all-grade (RR=1.58, [95% CI 1.25-1.99]) and high-grade (RR=3.92, [95% CI 1.46-10.52]) anemia and all-grade (RR=1.72, [95% CI 1.50-1.97]) and high-grade (RR=2.70, [95% CI 1.86-3.93]) lymphopenia.


Assuntos
Antineoplásicos/efeitos adversos , Doenças Hematológicas/etiologia , Neoplasias/complicações , Sirolimo/análogos & derivados , Antineoplásicos/uso terapêutico , Everolimo , Doenças Hematológicas/epidemiologia , Humanos , Incidência , Neoplasias/tratamento farmacológico , Razão de Chances , Viés de Publicação , Risco , Sirolimo/efeitos adversos , Sirolimo/uso terapêutico
8.
Cancer Treat Rev ; 39(7): 818-30, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23455076

RESUMO

BACKGROUND: The incidence and risk of unique toxicities associated with a multi-targeted tyrosine kinase inhibitor sunitinib, such as hypertension and thromboembolic events, have been previously reported. However, the incidence and risk of hematologic toxicities have been less well characterized. We performed an up-to-date meta-analysis of trials to evaluate the risk of sunitinib-related hematologic toxicities. METHODS: We searched Medline and the American Society of Clinical Oncology online database of meeting abstracts up to July 2012 for relevant clinical trials. Eligible studies included phase II and III trials and expanded access programs of sunitinib that reported adequate safety data profile reporting neutropenia, thrombocytopenia or anemia. The summary incidence, relative risk (RR) and 95% confidence intervals (CIs) were calculated. RESULTS: A total of 8,526 patients from 60 trials of sunitinib as a single agent revealed that the incidence of sunitinib-associated all-grade and high-grade (Grades 3 and 4) hematologic toxicities were, respectively: neutropenia: 42.1% and 12.8%; thrombocytopenia: 44.7% and 10.7% and anemia: 50.4% and 6.2%. Sunitinib-treated patients (2667 subjects from 10 randomized trials) had a significantly increased risk of all-grade (RR=3.58; 95% CI, 1.71-7.49) and high-grade (RR=3.32; 95% CI, 1.60-6.90) neutropenia, all-grade (RR=4.59; 95% CI, 2.76-7.63) and high-grade (RR=5.84; 95% CI, 2.22-15.41) thrombocytopenia and all-grade anemia (RR=1.15; 95% CI, 1.00-1.31). CONCLUSIONS: Sunitinib is associated with a significant increase in the risk of developing all-grade and high-grade neutropenia and thrombocytopenia and all-grade anemia compared with control.


Assuntos
Inibidores da Angiogênese/efeitos adversos , Antineoplásicos/efeitos adversos , Doenças Hematológicas/induzido quimicamente , Indóis/efeitos adversos , Neoplasias/complicações , Pirróis/efeitos adversos , Anemia/induzido quimicamente , Anemia/epidemiologia , Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Ensaios Clínicos como Assunto , Doenças Hematológicas/epidemiologia , Humanos , Incidência , Indóis/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Viés de Publicação , Pirróis/uso terapêutico , Risco , Sunitinibe , Trombocitopenia/induzido quimicamente , Trombocitopenia/epidemiologia
9.
Mol Biol Rep ; 39(12): 10227-34, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23076521

RESUMO

Our laboratory has developed a series of Gateway(®) compatible lentiviral expression systems for constitutive and conditional gene knock-down and over-expression. For tetracycline-regulated transgenic expression, we constructed a lentiviral "DEST" plasmid (pHR-TetCMV-Dest-IRES-GFP5) containing a tetracycline-responsive minimal CMV promoter, followed by an attP site-flanked DEST cassette (for efficient cloning of cDNAs by "Gateway(®)" recombination cloning) and green fluorescent protein (GFP) driven by an internal ribosomal entry site (IRES).This lentiviral bicistronic plasmid allows immediate FACS identification and characterization of successfully transfected cell lines. Although this system worked well with several cDNAs, we experienced serious problems with SLA, Bam and BMF. Particularly, we cloned the cDNA for human SLA (Src-like adapter), a candidate gene in GC-induced apoptosis, into this plasmid. The resulting construct (pHR-TetCMV-SLA-IRES-GFP5) was transfected into HEK 293-T packaging cells to produce viral particles for transduction of CEM-C7H2-2C8 cells. Although the construct produced many green fluorescent colonies at the HEK 293-T and the CEM-C7H2-2C8 level, we could not detect any SLA protein with α-SLA antibody from corresponding cell lysates. In contrast, the antibody readily detected SLA in whole cell lysate of HEK 293-T cells transfected with a GST-flagged SLA construct lacking IRES-GFP. To directly address the potential role of the IRES-GFP sequence, we cloned the SLA coding region into pHR-TetCMV-Dest, a vector that differs from pHR-TetCMV-Dest-IRES-GFP5 just by the absence of the IRES-GFP cassette. The resulting pHR-TetCMV-SLA construct was used for transfection of HEK 293-T cells. Corresponding lysates were assayed with α-SLA antibody and found positive. These data, in concert with previous findings, suggest that the IRES-GFP cassette may interfere with translation of certain smaller size cDNAs (like SLA) or generate fusion proteins and entail defective virus production in an unpredictable manner.


Assuntos
Glucocorticoides/fisiologia , Lentivirus/genética , Ativação Transcricional , Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Reguladoras de Apoptose , Proteína 11 Semelhante a Bcl-2 , Separação Celular , Citomegalovirus/genética , Citometria de Fluxo , Genes , Genes Reporter , Vetores Genéticos , Glucocorticoides/farmacologia , Proteínas de Fluorescência Verde/biossíntese , Proteínas de Fluorescência Verde/genética , Células HEK293 , Humanos , Proteínas de Membrana , Iniciação Traducional da Cadeia Peptídica , Plasmídeos/genética , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas pp60(c-src)/biossíntese , Proteínas Proto-Oncogênicas pp60(c-src)/genética , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Transdução Genética
10.
Vet Parasitol ; 170(1-2): 44-9, 2010 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-20233639

RESUMO

Cystic echinococcus poses an important economic and public health problem to Pakistan. Our study determined the prevalence and genotypes of Echinococcus present in domestic livestock and humans in Punjab, Pakistan. Out of 39,738 animals examined, 6.67% of animals were found infected. The prevalence and fertility of hydatid cysts was highest in camels (prevalence 17.29%; proportion fertile 95%), followed by sheep (prevalence 7.52%; proportion fertile 86.4%), buffalo (prevalence 7.19%; proportion fertile 84.3%), goats (prevalence 5.48%; proportion fertile 79.09%) and cattle (prevalence 5.18%; proportion fertile 75.25%). Phylogenetic analysis of the cytochrome oxidase-1 gene revealed that the common sheep strain (G1) and buffalo strain (G3) are cycling among livestock in Punjab and that these strains are highly adapted to goats, camels and cattle. Both human cysts were found to belong to the common sheep strain (G1) of E. granulosus, reinforcing this strain has the most potential for zoonotic transfer. Both morphological and molecular results support earlier studies suggesting that Echinococcus of sheep and buffalo origin is phenotypically and genetically similar which adds further evidence to support its recognition as one species viz, Echinococcus granulosus sensu stricto.


Assuntos
Animais Domésticos/parasitologia , Equinococose/veterinária , Echinococcus granulosus/genética , Filogenia , Zoonoses/parasitologia , Animais , DNA de Helmintos/química , DNA de Helmintos/genética , Equinococose/epidemiologia , Equinococose/genética , Echinococcus granulosus/ultraestrutura , Complexo IV da Cadeia de Transporte de Elétrons/química , Complexo IV da Cadeia de Transporte de Elétrons/genética , Humanos , Paquistão/epidemiologia , Reação em Cadeia da Polimerase/veterinária , Prevalência , Análise de Sequência de DNA
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