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1.
Front Oncol ; 11: 710585, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34568037

RESUMO

Background: Treatment of malignant melanoma has undergone a paradigm shift with the advent of immune checkpoint inhibitors (ICI) and targeted therapies. However, access to ICI is limited in low-middle income countries (LMICs). Patients and Methods: Histologically confirmed malignant melanoma cases registered from 2013 to 2019 were analysed for pattern of care, safety, and efficacy of systemic therapies (ST). Results: There were 659 patients with a median age of 53 (range 44-63) years; 58.9% were males; 55.2% were mucosal melanomas. Most common primary sites were extremities (36.6%) and anorectum (31.4%). Nearly 10.8% of the metastatic cohort were BRAF mutated. Among 368 non-metastatic patients (172 prior treated, 185 de novo, and 11 unresectable), with a median follow-up of 26 months (0-83 months), median EFS and OS were 29.5 (95% CI: 22-40) and 33.3 (95% CI: 29.5-41.2) months, respectively. In the metastatic cohort, with a median follow up of 24 (0-85) months, the median EFS for BSC was 3.1 (95% CI 1.9-4.8) months versus 3.98 (95% CI 3.2-4.7) months with any ST (HR: 0.69, 95% CI: 0.52-0.92; P = 0.011). The median OS was 3.9 (95% CI 3.3-6.4) months for BSC alone versus 12.0 (95% CI 10.5-15.1) months in any ST (HR: 0.38, 95% CI: 0.28-0.50; P < 0.001). The disease control rate was 51.55%. Commonest grade 3-4 toxicity was anemia with chemotherapy (9.5%) and ICI (8.8%). In multivariate analysis, any ST received had a better prognostic impact in the metastatic cohort. Conclusions: Large real-world data reflects the treatment patterns adopted in LMIC for melanomas and poor access to expensive, standard of care therapies. Other systemic therapies provide meaningful clinical benefit and are worth exploring especially when the standard therapies are challenging to administer.

2.
Adv Colloid Interface Sci ; 257: 58-70, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29887382

RESUMO

Natural forming clay halloysite is an emerging nanomaterial carrier for sustained drug delivery. These 50 nm diameter aluminosilicate tubes, with inner - alumina and outer - silica surface layers, can be loaded with 10-30 wt% of drug molecules, DNA and enzymes. The opposite charge of the inner and outer halloysite surface allow for selective drug adsorption inside or outside the clay nanotubes. The drug loaded halloysite enhanced the zeta potential of minus 50-60 mV allowing for stable aqueous nanocolloids. Halloysite nanoformulations provide an extended 10-20 h release profile, and may be functionalized (e.g., clogging tubes' end with polymers extending release time to 1-2 weeks or allowing for triggered release), which renders these clay nanostructures as promising controlled delivery systems. Recent studies demonstrate the potential of abundantly available halloysite clay nanotubes for life science applications, from drug delivery via oral or topical administration, to tissue scaffolds and regenerative medicine, while assessing their cellular internalization, stability, biosafety and biocompatibility are featured. The benefits and limitations of halloysite clay nanotubes are discussed, as well as the directions for future developments.


Assuntos
Silicatos de Alumínio/química , Materiais Biocompatíveis/química , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Nanotubos/química , Preparações Farmacêuticas/administração & dosagem , Preparações Farmacêuticas/química , Tecidos Suporte/química , Animais , Disciplinas das Ciências Biológicas/métodos , Argila , Liberação Controlada de Fármacos , Humanos , Tamanho da Partícula
4.
Indian J Pathol Microbiol ; 57(4): 530-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25308002

RESUMO

BACKGROUND AND AIMS: Breast cancer is one of the leading causes of mortality in Indian women. Although breast cancer is an epithelial malignancy, stroma plays a key role in its development and pathogenesis. Stromal markers are now emerging as novel markers in assessing the prognosis of invasive breast cancer and have not been studied extensively till date. The aim of the present study is to study the stromal expression of CD10 in breast carcinoma, find its relationship with other prognostic markers and study the role stroma plays in breast cancer pathogenesis. MATERIALS AND METHODS: A total of 70 cases of breast cancer were included in the study. Representative sections were taken and hematoxylin and eosin staining was done. Immunohistochemistry was performed with ER, PR, Her2neu and CD10. Stromal expression of CD10 (>10% stromal positivity was considered positive) in invasive breast carcinoma was noted and was statistically analyzed with different known prognostic markers of breast carcinoma. RESULTS: Stromal expression of CD10 was found to be significantly associated with increasing tumor grade (P = 0.04), increasing mitotic rate (P = 0.33), worsening prognosis (P = 0.01), ER negativity (P = 0.0001), Her2neu positivity (P = 0.19) and with molecular subtypes (CD10 positivity with the HER2 type, and CD10 negativity with Luminal type). No correlation was found between CD10 overexpression and PR, age, menopausal status, tumor size, lymph node positivity and tumor stage. CONCLUSIONS: This study gives substantial proof to the various models/research papers explaining the role of stroma/CD10 in breast cancer pathogenesis. Keeping the role stroma plays in predicting prognosis and tumor response, CD10 should be included as a routine pre-chemotherapy marker in breast carcinoma. Further studies should be performed to see the role stroma plays in hormonal expression and the usefulness of CD10 to predict treatment failure in breast carcinomas receiving neoadjuvant therapy.


Assuntos
Neoplasias da Mama/diagnóstico , Neprilisina/metabolismo , Adulto , Neoplasias da Mama/etiologia , Neoplasias da Mama/patologia , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Feminino , Humanos , Metaloproteinases da Matriz/biossíntese , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica/genética , Neprilisina/genética , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Inibidor Tecidual de Metaloproteinase-1/biossíntese , Fator de Crescimento Transformador beta/biossíntese
5.
Indian J Cancer ; 51(1): 18-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24947090

RESUMO

BACKGROUND: Plasma cell leukemia (PCL) is a rare aggressive variant of multiple myeloma (MM) characterized by a fulminant course and poor prognosis. Flow cytometry (FCM) is very useful in the diagnosis of the plasma cell leukemia. Herein, we present 10 cases of PCL. MATERIALS AND METHODS: We retrospectively studied immunophenotypic profile of 10 cases of PCL from Jan 2009 to Dec 2013 using 5 parameters, 6 color flow cytometric analysis. We also studied their clinical presentation and other laboratory findings. RESULTS: Common clinical features at presentation were weakness, bone pain, anemia, thrombocytopenia and osteolytic lesions. Plasma cell population were identified by strong expression of CD38 and co-expression of CD38 and CD138. CD56 was expressed in 20% cases. CD19 and CD117 were negative in all cases. CONCLUSIONS: Immunophenotyping is highly useful to differentiate PCL from other chronic lymphoproliferative disorders with plasmacytoid morphology as well as from non-neoplastic reactive plasma cells. Co-expression of CD38 and CD138 is a best combination to identify the plasma cells by using FCM.


Assuntos
Biomarcadores Tumorais/análise , Leucemia Plasmocitária/diagnóstico , Citometria de Fluxo , Seguimentos , Humanos , Imunofenotipagem , Leucemia Plasmocitária/imunologia , Prognóstico , Estudos Retrospectivos
6.
PET Clin ; 6(3): 313-26, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27156726

RESUMO

Positron emission tomography (PET) has been very well validated for assessing myocardial viability, and emerging sophisticated hybrid imaging technologies involving PET with other imaging modalities offer tremendous promise for delivering an in-depth but noninvasive evaluation of cardiac perfusion and function in various pathologic conditions during a single imaging session. Moreover, several new PET radiotracers in the research and preclinical arena are poised to enter the clinical setting in the foreseeable future. With such exciting developments on the horizon, cardiac PET and PET/computed tomography imaging, and potentially integrated cardiac PET/magnetic resonance imaging have become the focus of the molecular imaging paradigm for comprehensive cardiovascular assessment.

7.
J Control Release ; 128(3): 255-60, 2008 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-18479772

RESUMO

Stable nanocolloids of insoluble drugs with very high drug content (up to 90% wt) can be easily and reproducibly prepared through the application of the layer-by-layer (LbL) technology, alternate adsorption of oppositely charged polyelectrolytes on the surface of drug nanoparticles produced by ultrasonication of larger drug crystals. Such polymeric coating prevents drug nanoparticle aggregation and creates a firm polymeric shell on their surface. Drug release rate from such nanocolloidal particles can be easily controlled by assembling multilayer shells with variable shell density and thickness. Various additional functions, such as specific targeting ligands, can be easily attached to the surface on nanocolloidal particles of poorly soluble drugs by using a polymer with free reactive groups for the "outer" coating. This may represent a novel approach to preparing convenient dosage forms of poorly soluble drugs.


Assuntos
Antineoplásicos/química , Coloides , Nanopartículas , Paclitaxel/química , Sonicação , Tamoxifeno/química , Tecnologia Farmacêutica/métodos , Adsorção , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Química Farmacêutica , Composição de Medicamentos , Estabilidade de Medicamentos , Humanos , Cinética , Tamanho da Partícula , Solubilidade , Propriedades de Superfície
8.
Cancer Res ; 67(5): 2160-8, 2007 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-17332346

RESUMO

Molecular therapeutics identifies an aberration in tumors to select patients that benefit from molecular targeted therapy. Overexpression of eIF4E in histologically "tumor-free" surgical margins of head and neck squamous cell cancer (HNSCC) patients is an independent predictor of recurrence and is functionally activated through the Akt/mammalian target of rapamycin (mTOR) pathway. Although mTOR inhibitors are cytostatic agents, best used in combination therapy, we hypothesize that they can be used as long-term single agents in an HNSCC model of minimal residual disease (MRD). CCI-779, an mTOR inhibitor, arrested growth of a phosphatase and tensin homologue deleted on chromosome 10 (PTEN) abnormal HNSCC cell line FaDu, inhibiting phosphorylation of 4E-binding protein 1, resulting in increased association with eIF4E and inhibition of basic fibroblast growth factor and vascular endothelial growth factor. Fluorescence in situ hybridization detected PTEN abnormalities in 68% of patient tumors and 35% of tumor-free margins. CCI-779 inhibited growth of established tumors in nude mice. However, in the MRD model, there were significant differences in the tumor-free rate between the control (4%) and the treatment group (50%), and the median tumor-free time was 7 versus 18 days, respectively (P < 0.0001). In those animals that formed tumors, CCI-779 caused a significant decrease in the tumor volume. The Kaplan-Meier curve showed that CCI-779 significantly increased survival (P < 0.0001). The mTOR pathway was inhibited in peripheral blood mononuclear cells potential surrogate markers of response to therapy. Stable transfection of FaDu with luciferase allowed us to monitor the effects of CCI-779 with bioluminescence imaging in the MRD model. These results pave the way for a clinical trial using targeted molecular therapy with CCI-779 as a single agent for mTOR-activated residual cells.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Quinases , Sirolimo/análogos & derivados , Animais , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/patologia , Quimioterapia Adjuvante , Avaliação Pré-Clínica de Medicamentos , Dosagem de Genes , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Camundongos , Neoplasia Residual , PTEN Fosfo-Hidrolase/genética , Proteínas Quinases/fisiologia , Sirolimo/uso terapêutico , Serina-Treonina Quinases TOR , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
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