RESUMO
Triple negative breast cancer (TNBC) is most aggressive subtype of breast cancers with high probability of metastasis as well as lack of specific targets and targeted therapeutics. TNBC is characterized with unique tumor microenvironment (TME), which differs from other subtypes. TME is associated with induction of proliferation, angiogenesis, inhibition of apoptosis and immune system suppression, and drug resistance. Exosomes are promising nanovesicles, which orchestrate the TME by communicating with different cells within TME. The components of TME including transformed ECM, soluble factors, immune suppressive cells, epigenetic modifications and re-programmed fibroblasts together hamper antitumor response and helps progression and metastasis of TNBCs. Therefore, TME could be a therapeutic target of TNBC. The current review presents latest updates on the role of exosomes in modulation of TME, approaches for targeting TME and combination of immune checkpoint inhibitors and target chemotherapeutics. Finally, we also discussed various phytochemicals that alter genetic, transcriptomic and proteomic profiles of TME along with current challenges and future implications. Thus, as TME is associated with the hallmarks of TNBC, the understanding of the impact of different components can improve the clinical benefits of TNBC patients.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Exoma/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Microambiente Tumoral/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Epigênese Genética , Exoma/imunologia , Feminino , Humanos , Terapia de Alvo Molecular , Metástase Neoplásica , Células-Tronco Neoplásicas/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/patologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologiaRESUMO
Salacia oblonga Wall. is an endangered medicinal plant whose conservation is urgently needed, as it is extensively used in the Indian Ayurvedic system of medicine to treat diabetes mellitus. This study shows an easy, effective and simple method of conserving genetic identity and producing elite clones of S. oblonga through vegetative propagation. Vegetative propagation was achieved using roots (R), stems with leaves (SL) and stems without leaves (S) with different concentrations (0-500 ppm) of indole butyric acid (IBA). Explants S and SL showed maximum shooting response with 300 ppm IBA and explant R showed maximum response with 200 ppm IBA.
Assuntos
Diabetes Mellitus/terapia , Ayurveda , Plantas Medicinais/crescimento & desenvolvimento , Salacia/crescimento & desenvolvimento , Espécies em Perigo de Extinção , Indóis/metabolismo , Reguladores de Crescimento de Plantas , Folhas de Planta/metabolismo , Raízes de Plantas/metabolismo , Caules de Planta/metabolismoRESUMO
BACKGROUND: Saliva, "Mirror of body's health" has long been of particular interest as a substitute for blood for disease diagnosis and monitoring. The radiation effects on salivary glands are of particular interest in which salivary amylase is a good indicator of salivary glands function. Thus, estimation of these parameters represents a reasonable approach in evaluation of patient's risk for disease occurrence, intensity and prognosis. AIM OF STUDY: To evaluate and compare the pH and amylase levels in saliva of cancer patients prior to treatment, patients during treatment. MATERIALS AND METHODS: Saliva samples of 90 individuals were taken which were divided into 3 groups - 30 individuals without cancer, 30 cancer patients prior treatment and 30 cancer patients during treatment. Materials used were pH strips and pH meter, Salivary Amylase assay. RESULTS: Statistical analysis - ANOVA with post-hoc Tukey's test. 1) Significant decrease in salivary amylase levels - in cancer patients, during treatment when compared to others. 2) Significant decrease in salivary pH levels in newly diagnosed cancer patients prior to treatment. CONCLUSION: To conclude, pH strips and pH meter showed to be a useful tool in the measurement of pH of saliva in individuals with and without cancer. This study showed that cancer patients without treatment have a lower pH of saliva. Treatment increased the pH of the saliva to a more alkaline level whereas amylase levels decreased in those subjects. Therefore those parameters can be an area of further research with an increased sample size, which in-turn may help in opening the doors for new dimension in non invasive prognostic markers.
RESUMO
BACKGROUND: India is home to the largest population of patients with tuberculosis and tobacco users in the world. Smokeless tobacco use exceeds smoking and is increasing. There is no study to date that reports smokeless tobacco use before and after the diagnosis and treatment of tuberculosis. We assessed smokeless tobacco use among former patients of tuberculosis in Karnataka, India. METHODS: We conducted a community-based, cross sectional study among 202 men, who had been diagnosed and treated for tuberculosis (mean age 48 years), selected by multistage, random sampling. Using a semi-structured interview schedule, retrospective smoking and smokeless tobacco use were captured at eight time-points before and after the diagnosis and treatment of tuberculosis. RESULTS: Most patients suspended tobacco use during treatment. A high 44% prevalence of smokeless tobacco use 6 months before diagnosis was reduced to just 8% during the intensive phase of treatment and climbed to 27% 6 months after treatment. The tobacco use relapse rate 6 months after completion of treatment was higher for smokeless tobacco use (52%, 95% CI 41%-62%) than for smoking (36%, 95% CI 26%-45%). We also found that many patients who were advised to quit smoking continued using smokeless tobacco after completion of treatment. Additionally, new smokeless tobacco use was documented. Of the 11 new exclusive smokeless tobacco users, 10 shifted from smoking to smokeless tobacco use as a form of harm reduction. CONCLUSION: Patients with tuberculosis are advised by their doctors, at the time of diagnosis, to quit smoking. Several patients shift from smoking to smokeless tobacco use, which needs to be addressed while providing tobacco cessation services.
Assuntos
Avaliação das Necessidades/estatística & dados numéricos , Abandono do Uso de Tabaco/estatística & dados numéricos , Tabaco sem Fumaça/efeitos adversos , Tuberculose Pulmonar/epidemiologia , Adulto , Idoso , Estudos Transversais , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto JovemRESUMO
BACKGROUND: In 2010, WHO expanded previously-recommended indications for anti-retroviral treatment to include all HIV-infected TB patients irrespective of CD4 count. India, however, still limits ART to those TB patients with CD4 counts <350/mm(3) or with extrapulmonary TB manifestations. We sought to evaluate the additional number of patients that would be initiated on ART if India adopted the current 2010 WHO ART guidelines for HIV-infected TB patients. METHODS: We evaluated all TB patients recorded in treatment registers of the Revised National TB Control Programme in June 2010 in the high-HIV prevalence state of Karnataka, and cross-matched HIV-infected TB patients with ART programme records. RESULTS: Of 6182 TB patients registered, HIV status was ascertained for 5761(93%) and 710(12%) were HIV-infected. 146(21%) HIV-infected TB patients were on ART prior to TB diagnosis. Of the remaining 564, 497(88%) were assessed for ART eligibility; of these, 436(88%) were eligible for ART according to 2006 WHO ART guidelines. Altogether, 487(69%) HIV-infected TB patients received ART during TB treatment. About 80% started ART within 8 weeks of TB treatment and 95% received an efavirenz based regimen. CONCLUSION: In Karnataka, India, about nine out of ten HIV-infected TB patients were eligible for ART according to 2006 WHO ART guidelines. The efficiency of HIV case finding, ART evaluation, and ART initiation was relatively high, with 78% of eligible HIV-infected patients actually initiated on ART, and 80% within 8 weeks of diagnosis. ART could be extended to all HIV-infected TB patients irrespective of CD4 count with relatively little additional burden on the national ART programme.
Assuntos
Terapia Antirretroviral de Alta Atividade/estatística & dados numéricos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Guias de Prática Clínica como Assunto , Tuberculose/complicações , Organização Mundial da Saúde , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Índia , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Fatores de Tempo , Adulto JovemRESUMO
The capacity of microwave non-destructive testing (NDT) technique to characterize the matrix property of binary polymeric films for use as transdermal drug delivery system was investigated. Hydroxypropylmethylcellulose (HPMC) and polyethylene glycol (PEG) 3000 were the choice of polymeric matrix and plasticizer, respectively with loratadine as the model drug. Both blank and drug loaded HPMC-PEG 3000 films were prepared using the solvent-evaporation method. These films were conditioned at the relative humidity of 25, 50 and 75% prior to physicochemical characterization using the established methods of ultra-violet spectrophotometry, differential scanning calorimetry and Fourier transform infrared spectroscopy methods, as well as, novel microwave NDT technique. Blank films exhibited a greater propensity of polymer-polymer interaction at the O-H domain upon storage at a lower level of relative humidity, whereas drug loaded films exhibited a greater propensity of polymer-polymer, polymer-plasticizer and/or drug-polymer interaction via the O-H, C-H and/or aromatic C=C functional groups when they were stored at a lower or moderate level of relative humidity. The absorption and transmission characteristics of both blank and drug loaded films for microwave varied with the state of polymer-polymer, polymer-plasticizer, and/or drug-polymer interaction of the matrix. The measurements of microwave NDT test at 8 and 12 GHz were sensitive to the polar fraction of film involving functional group such as O-H moiety and the less polar environment of matrix consisting of functional groups such as C-H and aromatic C=C moieties. The state of interaction between polymer, plasticizer and/or drug of a binary polymeric film can be elucidated through its absorption and transmission profiles of microwave.