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1.
Arch Virol ; 160(2): 499-508, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25395243

RESUMEN

Saffron and its components have been suggested as promising candidates for cancer prevention. Carotenoids and monoterpene aldehydes are two potent ingredients of saffron. The goal of the current study was to investigate the anti-tumor effect of chemo-immunotherapy using saffron and its ingredients followed by E7-NT (gp96) DNA vaccine against tumors expressing the E7 protein of human papillomavirus. The in vitro cytotoxic and apoptotic effects of aqueous saffron extract and its components were evaluated in malignant TC-1 and non-malignant COS-7 cell lines. Then, multimodality treatments using E7-NT (gp96) DNA vaccine combined with saffron extract and its ingredients as well as single-modality treatments were tested for their efficacy in inhibiting large and bulky tumor growth. Saffron and its components exerted a considerable anti-tumor effect through prevention of cell growth and stimulation of programmed cell death. Furthermore, 100 % of mice treated with crocin were tumor-free, in contrast to DNA vaccine alone (~66.7 %) and DNA + crocin (~33.3 %) indicating the high potency of crocin as a chemotherapeutic agent. Interestingly, the multimodality treatment using DNA vaccine along with picrocrocin augmented the anti-tumor effects of picrocrocin. Thus, the combination of DNA vaccine with saffron extract and crocin at certain concentrations did not potentiate protective and therapeutic effects compared to mono-therapies for the control of TC-1 tumors.


Asunto(s)
Antineoplásicos/uso terapéutico , Vacunas contra el Cáncer/uso terapéutico , Carotenoides/uso terapéutico , Crocus/química , Ciclohexenos/uso terapéutico , Glucósidos/uso terapéutico , Neoplasias/terapia , Proteínas E7 de Papillomavirus/inmunología , Vacunas contra Papillomavirus/uso terapéutico , Terpenos/uso terapéutico , Animales , Apoptosis/efectos de los fármacos , Células COS , Vacunas contra el Cáncer/inmunología , Línea Celular Tumoral , Chlorocebus aethiops , Terapia Combinada , Femenino , Inmunoterapia , Ratones , Ratones Endogámicos C57BL , Neoplasias/tratamiento farmacológico , Neoplasias/prevención & control , Vacunas contra Papillomavirus/inmunología , Fitoterapia/métodos , Extractos Vegetales/uso terapéutico , Polietileneimina/farmacología , Transformación Genética , Vacunación , Vacunas de ADN/inmunología , Vacunas de ADN/uso terapéutico
2.
Phytother Res ; 28(8): 1252-9, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24711260

RESUMEN

Indukantha Ghritha (IG), a polyherbal drug used for centuries in Ayurveda, is claimed to be successful in the treatment of respiratory diseases and as a rejuvenating drug. To date, little is known about the immunomodulatory role of IG in recurrent upper respiratory tract infections (RURIs). This study was designed to scientifically validate and evaluate the immunological response mechanisms in patients with RURI. Primarily, immunological functioning of the lymphocyte subsets, Th1 and Th2 cytokines, and immunoglobulins was evaluated before and after administration of IG in patients (n=48) and normal subjects (n=25) for a period of 28 days. Flow cytometry revealed a significant increase in the CD3+, CD4+ T cells and CD56+ natural killer cells with a concomitant reduction of percentage of B cells during IG treatment. Increased Th1 cytokines, IL-2 and IFN-γ, and decreased Th2 cytokine, IL-4, were also observed with IG treatment. IgG was markedly decreased, and IgM was increased with no changes in IgA. Assessment of liver and kidney functions and cholesterol levels was within normal limits in patients administered IG, which reinforces its drug utility as a non-toxic polyherbal drug. Overall, IG provides symptomatic relief by functioning as a potent immunostimulator that can induce type 1 and decrease type 2 immune responses thereby maintaining immunological homeostasis in RURI patients.


Asunto(s)
Medicina Ayurvédica , Preparaciones de Plantas/uso terapéutico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/inmunología , Adolescente , Adulto , Linfocitos B/inmunología , Linfocitos T CD4-Positivos/inmunología , Estudios de Casos y Controles , Femenino , Homeostasis , Humanos , Interferón gamma/inmunología , Interleucina-2/inmunología , Interleucina-4/inmunología , Células Asesinas Naturales/inmunología , Subgrupos Linfocitarios , Masculino , Persona de Mediana Edad , Proyectos Piloto , Plantas Medicinales , Balance Th1 - Th2 , Adulto Joven
3.
Front Microbiol ; 14: 1301478, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38029101

RESUMEN

Background: S. Typhi is a Gram-negative bacterium that causes typhoid fever in humans. Its virulence depends on the TolC outer membrane pump, which expels toxic compounds and antibiotics. However, the role of TolC in the host cell adhesion and invasion by S. Typhi is unclear. Objective: We aimed to investigate how deleting the tolC affects the adhesion and invasion of HT-29 epithelial and THP-1 macrophage cells by S. Typhi in vitro. Methods: We compared the adhesion and invasion rates of the wild-type and the tolC mutant strains of S. Typhi using in vitro adhesion and invasion assays. We also measured the expression levels of SPI-1 genes (invF, sipA, sipC, and sipD) using quantitative PCR. Results: We found that the tolC mutant showed a significant reduction in adhesion and invasion compared to the wild-type strain in both cell types. We also observed that the expression of SPI-1 genes was downregulated in the tolC mutant. Discussion: Our results suggest that TolC modulates the expression of SPI-1 genes and facilitates the adhesion and invasion of host cells by S. Typhi. Our study provides new insights into the molecular mechanisms of S. Typhi pathogenesis and antibiotic resistance. However, our study is limited by the use of in vitro models and does not reflect the complex interactions between S. Typhi and host cells in vivo.

4.
ScientificWorldJournal ; 2012: 361382, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22593679

RESUMEN

Antitumor activity of polysaccharide PST001 isolated from the seed kernel of Tamarindus indica was evaluated using different cancer cell lines. Human cancer cell lines A549, KB, and MCF-7 and murine cancer cell lines DLA and EAC were treated with PST001 and cell growth inhibition was assessed by MTT assay. In vivo studies were carried out for toxicity, tumor reduction and immunomodulation. The respective IC(50) of PST001 in A549, KB, and DLA was at 80.72, 190.99, and 91.14 µg/mL. Significant tumor reduction was obtained in both DLA and EAC tumors on treatment with PST001 which was more prominent when PST001 was administered with CTX/5-fluorouracil. Increase in total WBC, CD4(+) T-cell population, and bone marrow cellularity suggested strong immunomodulatory activity for this compound. No significant abnormality was observed in toxicity studies. Thus the results of the present study suggest that PST001 has immunomodulatory and tumor inhibitory activities and has the potential to be developed as an anticancer agent and immunomodulator either as a sole agent or as an adjuvant to other chemotherapeutic drugs.


Asunto(s)
Antineoplásicos/farmacología , Factores Inmunológicos/farmacología , Polisacáridos/farmacología , Semillas/química , Tamarindus/química , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/toxicidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/farmacología , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/farmacología , Humanos , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/toxicidad , Concentración 50 Inhibidora , Masculino , Ratones , Ratones Endogámicos BALB C , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/patología , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacología , Extractos Vegetales/toxicidad , Polisacáridos/administración & dosificación , Polisacáridos/toxicidad , Pruebas de Toxicidad , Carga Tumoral/efectos de los fármacos
5.
ScientificWorldJournal ; 2012: 439479, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22666123

RESUMEN

Eupatorium odoratum (EO) contains many biologically active compounds, the anticancer effects of which are not well documented. This study evaluates the cytotoxic effects and mechanism of action of EO extracts on MCF-7 and Vero cell lines. Evaluation of the cytotoxic activity using MTT assay, morphological alterations, and apoptosis were carried out. Autophagy was evaluated by LC3-A protein expression. Cytotoxic activity, membrane blebbing and ballooning at 24 hours, replacement by mass vacuolation, and double membrane vesicles mimicking autophagy and cell death were observed in the cancer cells. No apoptosis was observed by DNA fragmentation assay. Overexpression of LC3-A protein indicated autophagic cell death. Cell cycle analysis showed G0 and G2/M arrest. The Vero cells did not show significant cell death at concentrations <100 µg/mL. These results thus suggest that acetone and ethyl acetate extracts of EO induce cell death through induction of autophagy and hold potential for development as potential anticancer drugs.


Asunto(s)
Autofagia/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Chromolaena/química , Extractos Vegetales/farmacología , Acetatos/química , Acetona/química , Animales , Línea Celular Tumoral , Chlorocebus aethiops , Humanos , Técnicas In Vitro , Células Vero
6.
Int J Mol Sci ; 13(5): 5607-5627, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22754319

RESUMEN

In the present study, we aimed to preincubate MCF-10A cells with pioglitazone and/or serum-rich growth media and to determine adhesive and non-adhesive interactions of the preincubated MCF-10A cells with BT-474 cells. For this purpose, the MCF-10A cells were preincubated with pioglitazone and/or serum-rich growth media, at appropriate concentrations, for 1 week. The MCF-10A cells preincubated with pioglitazone and/or serum-rich growth media were then co-cultured adhesively and non-adhesively with BT-474 cells for another week. Co-culture of BT-474 cells with the preincubated MCF-10A cells, both adhesively and non-adhesively, reduced the growth of the cancer cells. The inhibitory effect of the preincubated MCF-10A cells against the growth of BT-474 cells was likely produced by increasing levels of soluble factors secreted by the preincubated MCF-10A cells into the conditioned medium, as immunoassayed by ELISA. However, only an elevated level of a soluble factor distinguished the conditioned medium collected from the MCF-10A cells preincubated with pioglitazone and serum-rich growth medium than that with pioglitazone alone. This finding was further confirmed by the induction of the soluble factor transcript expression in the preincubated MCF-10A cells, as determined using real-time PCR, for the above phenomenon. Furthermore, modification of the MCF-10A cells through preincubation did not change the morphology of the cells, indicating that the preincubated cells may potentially be injected into mammary fat pads to reduce cancer growth in patients or to be used for others cell-mediated therapy.


Asunto(s)
Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Medios de Cultivo Condicionados/farmacología , Hipoglucemiantes/farmacología , Tiazolidinedionas/farmacología , Mama/efectos de los fármacos , Mama/patología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Adhesión Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Técnicas de Cocultivo , Medios de Cultivo Condicionados/metabolismo , Femenino , Humanos , Pioglitazona , Suero/metabolismo
7.
Int J Mol Sci ; 11(5): 2188-99, 2010 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-20559509

RESUMEN

Chrysin is a natural flavonoid currently under investigation due to its important biological anti-cancer properties. In most of the cancer cells tested, chrysin has shown to inhibit proliferation and induce apoptosis, and is more potent than other tested flavonoids in leukemia cells, where chrysin is likely to act via activation of caspases and inactivation of Akt signaling in the cells. Moreover, structure-activity relationships have revealed that the chemical structure of chrysin meets the key structural requirements of flavonoids for potent cytotoxicity in leukemia cells. It is possible that combination therapy or modified chrysin could be more potent than single-agent use or administration of unmodified chrysin. This study may help to develop ways of improving the effectiveness of chrysin in the treatment of leukemia and other human cancers in vitro.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Flavonoides/farmacología , Leucemia , Antineoplásicos/química , Caspasas/metabolismo , Línea Celular Tumoral , Activación Enzimática/efectos de los fármacos , Flavonoides/química , Humanos , Leucemia/tratamiento farmacológico , Leucemia/metabolismo , Leucemia/patología , Proteínas de Neoplasias/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Relación Estructura-Actividad
8.
Int J Med Microbiol ; 299(3): 177-85, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18845475

RESUMEN

Bacterial persistence is of major concern worldwide in the control of a number of bacterial infections. The carriers who are asymptomatic act as reservoirs of the bacteria. Knowledge of the host response, of the persistence process, and of the potential of biological mediators as diagnostic markers is essential towards development of prophylactic and treatment modalities for these diseases. Immune mechanisms related to recognition and elimination of the bacteria play pivotal roles in the control of bacterial infections. The majority of the studies on bacterial infections detail the immune mechanisms in the active phase of infection, and reports on the immune status in carriers are scanty. The present review describes the role of recognition molecules (TLRs) and the immune mediators (cytokines) in bacterial persistence. It appears that the TLR-mediated induction of cytokine profiles differs in active infection and bacterial persistence, with an active Th1 response being beneficial for the clearance of a high load of bacteria and at the same time conducive for the persistence of low bacterial load. Immunomodulation aiming at stimulation of the immune responses should be carried out with care as it could give rise to a carrier state in individuals with low load of the bacteria.


Asunto(s)
Portador Sano/inmunología , Portador Sano/microbiología , Citocinas/inmunología , Infecciones por Mycobacterium/inmunología , Infecciones por Salmonella/inmunología , Receptores Toll-Like/inmunología , Humanos
9.
Immunobiology ; 213(8): 641-9, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18765169

RESUMEN

Indukantha Ghritha (IG) is a polyherbal preparation consisting of 17 plant components widely prescribed by ayurvedic physicians for various ailments. Though it is a known ayurvedic drug, no attempt has been made to scientifically validate its mechanism of action. Preliminary studies in our laboratory showed IG to possess considerable immunomodulatory effects with a Th1 type of immune response. In this regard, we attempted to elucidate its role as an adjuvant to cancer chemotherapy. BALB/c mice were administered IG, for a period of 14 days and parameters such as Hb, total and differential WBC count, bone marrow cellularity, lymphocyte proliferation and function, macrophage phagocytosis and tumor remission were studied. Administration of IG could inhibit tumor development in mice challenged with Dalton's lymphoma ascites. IG-induced leukopoiesis and enhanced median survival time as well as life span in tumor bearing animals. Macrophage phagocytic capacity was also elevated. Flow cytometric analysis of lymphocyte subsets and MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H-tetrazolium salt] assay for lymphocyte proliferation, yielded promising results which reinforces its use as an adjuvant to cancer chemotherapy. The polyherbal drug could reverse cyclophosphamide-induced myelosuppression in control tumor bearing animals significantly to values near or above normal levels. These results demonstrate the potential of IG, especially in several immunosuppressed conditions and patients suffering from leukopenia as a consequence of cancer chemotherapy.


Asunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Quimioterapia Adyuvante , Linfoma/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Adyuvantes Inmunológicos/efectos adversos , Animales , Proliferación Celular/efectos de los fármacos , Quimioterapia Adyuvante/efectos adversos , Interacciones de Hierba-Droga , Inyecciones Intraperitoneales , Leucopenia/inducido químicamente , Leucopenia/tratamiento farmacológico , Leucopenia/inmunología , Linfoma/inmunología , Linfoma/patología , Medicina Ayurvédica , Ratones , Ratones Endogámicos BALB C , Trasplante de Neoplasias , Fagocitosis/efectos de los fármacos , Fagocitosis/inmunología , Extractos Vegetales/efectos adversos , Células TH1/metabolismo , Células TH1/patología
10.
J Clin Diagn Res ; 11(6): DC10-DC13, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28764158

RESUMEN

INTRODUCTION: Typhoid fever remains a scourge of humanity, especially in developing and under-developed countries due to poor sanitation and food hygiene. Diagnostic methods available for detection of this disease are not satisfactory due to a lack of sensitive, specific, rapid and convenient diagnostic test kits available in the market. AIM: To evaluate the feasibility of a Dot-EIA method for Ig-class specific salivary antibody detection for diagnosis of typhoid fever. MATERIALS AND METHODS: Paired saliva and serum samples were collected in the year 2010 from patients and normal volunteers in Hospital Universiti Sains Malaysia, Kelantan, Malaysia, which is endemic for typhoid fever. A total of 11 culture-confirmed typhoid fever patients, 43 non-typhoid fever patients and 53 normal human control subjects were evaluated for antibodies against a 50 kDa antigen specific for Salmonella Typhi using Dot-EIA. RESULTS: Ig class-specific screening of the test samples showed a higher sensitivity for IgA (90.9%) compared to either IgG (72.7%) or IgM (72.7%) antibodies in saliva, but for serum, IgG (90.9%) had a higher degree of sensitivity compared to IgA (36.4%) and IgM (63.6%). Combining all isotypes (IgA, IgG or IgM), serum showed a higher sensitivity (100.0%) compared to saliva (90.9%). Also, the specificity for serum (100.0%) was much higher than saliva (85.4%). CONCLUSION: Salivary IgA anti-50kDa antibody was found to be more suitable biomarker for routine screening, whereas serum IgG was more suitable for confirmatory test as it has higher specificity. Nevertheless, salivary IgA Dot-EIA is a convenient method for rapid testing, such as for Point-of-Care Diagnostics (POCD) and field epidemiological studies, due to its non-invasive nature and ease of use.

11.
Virus Res ; 115(1): 85-90, 2006 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16139912

RESUMEN

Treatment failure in nasopharyngeal carcinoma (NPC) is mainly due to local and regional recurrence and at present lacks a marker to identify such cases. VEGF, a potent endothelial cell mitogen and vascular permeability-inducing agent, plays a critical role in tumor growth and neo-vascularisation. VEGF expression was assessed in 103 NPC and 26 benign adenoid lesions by immunohistochemistry and Epstein Bar Virus (EBV) presence by PCR using primers directed against EBNA-1 gene. The localization of the virus to the tumour cells was confirmed by in situ hybridization using EBER in situ hybridization. Over expression of VEGF was seen in 67% of NPC cases. Higher expression of VEGF in EBV positive tumours was related to higher rate of recurrence, nodal positivity and lower survival. This is the first report evaluating the correlation between VEGF expression levels, EBV status and recurrence in Indian NPC. The results point towards the potential of the expression pattern of VEGF as a tumor marker for the early diagnosis of metastastic NPC and also show that presence of EBV is related to up regulation of VEGF.


Asunto(s)
Carcinoma/metabolismo , Carcinoma/virología , Herpesvirus Humano 4/aislamiento & purificación , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/virología , Nasofaringe/metabolismo , Nasofaringe/virología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Biomarcadores de Tumor , Antígenos Nucleares del Virus de Epstein-Barr/genética , Herpesvirus Humano 4/genética , Humanos , Ganglios Linfáticos/metabolismo , Ganglios Linfáticos/virología , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/virología , Reacción en Cadena de la Polimerasa
12.
Cytotechnology ; 68(5): 1771-87, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26754842

RESUMEN

The goal of this study was to determine the effects of PGZ and MK886 on the mRNA expression of PPARα and other associated genes in MDA-MB-231 cells, and the biological mechanisms induced by both drugs were also assessed. The levels of PPARα mRNA expression in PGZ-treated and MK886-treated MDA-MB-231 cells were determined using real-time PCR; the growth inhibitory effects of PGZ and MK886 were determined using the trypan blue exclusion assay; the induction of apoptosis by PGZ and MK886 was determined using DNA fragmentation assay and real-time PCR; and the invasion of PGZ-treated and MK886-treated MDA-MB-231 cells was determined using the wound healing and transwell migration assays. In addition, we correlated the expression of PPARα mRNA with other genes, including PPARγ, FGF4 and 5LOX, in drug-treated MDA-MB-231 cells. Our results demonstrated that the treatment of MDA-MB-231 cells with PGZ increased the expression of PPARα/γ mRNA and that this expression could be inhibited by treatment with MK886. Both drugs reduced the viability of MDA-MB-231 cells independently of PPARα/γ mRNA expression but did not induce apoptosis. The wound caused by invasion was not healed by PGZ-treated MDA-MB-231 cells, but it was healed by MK886-treated cancer cells, indicating that the reduction of invasion in PGZ-treated MDA-MB-231 cells was eliminated by treatment with MK886, and this finding was validated by the transwell migration assay. This phenomenon might also be associated with the expression of PPARα/γ, FGF4 and 5LOX mRNA in the treated cancer cells. This study provides useful information regarding the mRNA expression levels of PPARα and other related genes in MDA-MB-231 cells. These genes could be attractive targets for reducing the invasion of breast cancer.

13.
J Clin Diagn Res ; 10(6): DM01-3, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27504289

RESUMEN

INTRODUCTION: The Salmonella typhi (S. typhi) haemolysin E protein (HlyE) has been shown to be a sensitive and specific antigen for the detection of typhoid fever through the detection of anti-HlyE antibodies in sera. Saliva can also be a useful diagnostic fluid as it also contains antibodies against bacterial pathogens. AIM: This study aims to evaluate the potential detection of salivary anti-HlyE antibodies as a diagnosis of typhoid fever. MATERIALS AND METHODS: Saliva was collected from acute typhoid patients (n=16) who presented at Hospital Universiti Sains Malaysia with prolonged fever of more than five days and were positive for S. Typhi blood culture. Saliva was also collected from convalescent typhoid patients (n=11), patients with other febrile fevers (n=15), and from healthy individuals (n=25). An ELISA was developed to detect the presence of IgA antibodies against HlyE in the saliva of typhoid patients. RESULTS: The acute typhoid group had a higher mean absorbance value of 1.496 compared to the convalescent typhoid (0.538), other febrile fevers (0.678), and healthy individuals (0.457) group. CONCLUSION: This study demonstrated the utility of salivary anti-HlyE IgA antibody as a biomarker for the diagnosis of typhoid fever. Follow-up studies with a larger sample size will allow the optimization of the sensitivity and specificity of the assay. This non-invasive method can be useful for mass screening programs.

14.
Dent Res J (Isfahan) ; 12(4): 307-14, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26288619

RESUMEN

BACKGROUND: The role of retinoblastoma (Rb) protein in cell cycle regulation prompted us to take up this study with the aim of assessing its role in the progression of oral cancer and to correlate with various clinicopathological parameters, including habits such as smoking, Paan chewing, and alcoholism. MATERIALS AND METHODS: This observational study included surgical specimens from 10 apparently normal oral mucosa, 14 oral reactive lesions (ORL), 29 precancerous lesions and 43 oral cancers. The expression of Rb protein in tissue samples were evaluated by immunohistochemistry and correlated with clinicopathological data. The percentage and mean expression of Rb protein were statistically analyzed using Student's t-test and P < 0.05 was considered as statistically significant difference. RESULTS: The expression of Rb protein was found to increase from normal, ORL, precancerous lesions to cancers. A consistently high expression of Rb protein was seen in oral cancers, with an increase in well-differentiated and moderately differentiated tumors. Patients with combined habits of Paan chewing, smoking, and alcohol consumption had a higher expression compared with those without habits. CONCLUSION: Within the limitations of this study, it seems that overexpression of Rb protein noted in oral cancer, with an increase in well and moderately differentiated tumors suggest a possible role of Rb in differentiation. The high expression of Rb in patients with combined habits of Paan chewing, smoking and alcohol consumption indicates that Rb pathway may be altered in habit-related oral malignancies.

15.
Int J Biochem Cell Biol ; 59: 153-66, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25541375

RESUMEN

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an attractive target for cancer therapy due to its ability to selectively induce apoptosis in cancer cells, without causing significant toxicity in normal tissues. We previously reported that galactoxyloglucan (PST001) possesses significant antitumor and immunomodulatory properties. However, the exact mechanism in mediating this anticancer effect is unknown. This study, for the first time, indicated that PST001 sensitizes non-small cell lung cancer (A549) and nasopharyngeal (KB) cells to TRAIL-mediated apoptosis. In vitro studies suggested that PST001 induced apoptosis primarily via death receptors and predominantly activated caspases belonging to the extrinsic apoptotic cascade. Microarray profiling of PST001 treated A549 and KB cells showed the suppression of survivin (BIRC5) and anti-apoptotic Bcl-2, as well as increased cytochrome C. TaqMan low density array analysis of A549 cells also confirmed that the induction of apoptosis by the polysaccharide occurred through the TRAIL-DR4/DR5 pathways. This was finally confirmed by in silico analysis, which revealed that PST001 binds to TRAIL-DR4/DR5 complexes more strongly than TNF and Fas ligand-receptor complexes. In summary, our results suggest the potential of PST001 to be developed as an anticancer agent that not only preserves innate biological activity of TRAIL, but also sensitizes cancer cells to TRAIL-mediated apoptosis.


Asunto(s)
Apoptosis/efectos de los fármacos , Glucanos/farmacología , Ligando Inductor de Apoptosis Relacionado con TNF/farmacología , Anexina A5/metabolismo , Proteínas Reguladoras de la Apoptosis , Caspasas/metabolismo , Línea Celular Tumoral , Permeabilidad de la Membrana Celular/efectos de los fármacos , Forma de la Célula/efectos de los fármacos , Tamaño de la Célula/efectos de los fármacos , Cromatina/efectos de los fármacos , Cromatina/metabolismo , Citometría de Flujo , Colorantes Fluorescentes/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Simulación del Acoplamiento Molecular , Análisis de Secuencia por Matrices de Oligonucleótidos , Propidio/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Reproducibilidad de los Resultados , Espectrometría de Fluorescencia , Coloración y Etiquetado
16.
Asia Pac J Public Health ; 27(2): NP2740-8, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23000800

RESUMEN

Chronic carriers of Salmonella Typhi act as reservoirs for the organism and become the agents of typhoid outbreaks in a community. In this study, chronic carriers in Kelantan, Malaysia were first identified using the culture and polymerase chain reaction method. Then, a novel serological tool, designated Typhidot-C, was evaluated in retrospect using the detected individuals as control positives. Chronic carriage positive by the culture and polymerase chain reaction method was recorded at 3.6% (4 out of 110) among individuals who previously had acute typhoid fever and a 9.4% (10 out of 106) carriage rate was observed among food handlers screened during outbreaks. The Typhidot-C assay was able to detect all these positive carriers showing its potential as a viable carrier screening tool and can be used for efficient detection of typhoid carriers in an endemic area. These findings were used to establish the first carrier registry for S Typhi carriers in Malaysia.


Asunto(s)
Portador Sano/epidemiología , Sistema de Registros/estadística & datos numéricos , Salmonella typhi/aislamiento & purificación , Fiebre Tifoidea/epidemiología , Heces/microbiología , Manipulación de Alimentos , Humanos , Técnicas para Inmunoenzimas , Malasia/epidemiología , Reacción en Cadena de la Polimerasa
17.
J Soc Gynecol Investig ; 9(2): 111-5, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-11963831

RESUMEN

OBJECTIVE: Although nm23-H1 protein expression has been related to invasion in many cancers, its expression and prognostic significance in complete hydatidiform moles has not yet been investigated. The search for biologic parameters in molar placentas, which are useful for identifying patients who show myometrial invasion of the tumor, is crucial. We examined the clinical significance of nm23-H1 expression in complete hydatidiform mole. METHODS: Sections of 105 cases of complete hydatidiform moles (including 25 cases of invasive mole) and 95 cases of gestational age--matched normal placentas were immunohistochemically stained with anti-nm23-H1 antibody, which recognizes the nm23-H1/NDP kinase A gene product. RESULTS: Expression of nm23-H1 was detected in the cytotrophoblasts and syncytiotrophoblasts of molar placentas and normal placentas, whereas it was not detected in stromal tissue. Expression of nm23-H1 showed a negative relation to invasion, suggesting its use as a potential marker of myometrial invasion in complete hydatidiform moles. CONCLUSION: nm23-H1 expression could be used as a marker for accurate evaluation of myometrial invasion in complete hydatidiform mole.


Asunto(s)
Mola Hidatiforme/química , Mola Hidatiforme/patología , Proteínas de Unión al GTP Monoméricas/análisis , Miometrio/patología , Nucleósido-Difosfato Quinasa , Factores de Transcripción/análisis , Neoplasias Uterinas/química , Gonadotropina Coriónica Humana de Subunidad beta/sangre , Femenino , Edad Gestacional , Humanos , Inmunohistoquímica , Nucleósido Difosfato Quinasas NM23 , Placenta/química , Embarazo , Trofoblastos/química , Neoplasias Uterinas/patología
18.
Pathol Oncol Res ; 8(2): 125-8, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-12172576

RESUMEN

Endothelial cell adhesion molecules (CAMs) are important in tumorigenesis and host defense mechanism. Their status in breast cancer with regard to nodal invasion is not yet known. Hence we looked at the expression of three important CAMs: VCAM, ICAM and E-selectin. A downregulation of all these CAMs was noted in node positive breast cancer in comparison to node negative cases. This suggests shedding of these molecules in cases with nodal metastasis which might help the tumor cells to escape the host defense mechanism. On multi-variate analysis, VCAM alone emerged as an independent predictor of nodal metastasis.


Asunto(s)
Neoplasias de la Mama/metabolismo , Selectina E/metabolismo , Molécula 1 de Adhesión Intercelular/metabolismo , Molécula 1 de Adhesión Celular Vascular/metabolismo , Neoplasias de la Mama/patología , Comunicación Celular , Regulación hacia Abajo , Femenino , Humanos , Técnicas para Inmunoenzimas , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Pronóstico
19.
Indian J Pathol Microbiol ; 47(2): 181-5, 2004 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-16295463

RESUMEN

Nasopharyngeal carcinoma (NPC) is a rare malignancy world-wide. It shows an increasing trend in the southern parts of India. Genetic alterations brought about by environmental factors, HPV and EBV are thought to be crucial for NPC carcinogenesis. This study reports for the first time the incidence of HPV infection in NPC in Southern India. Detection of HPV was carried out in 36 NPC and 10 adenoid lesions by immunohistochemical analysis. 38.8% of NPC were positive for HPV with higher positivity in WHO Type I and WHO Type II cancers. One among 10 adenoid lesions also showed presence of HPV. The patients belonged to low socio-economic status and had exposure to either tobacco or alcohol alone or in combination or kitchen smoke.


Asunto(s)
Neoplasias Nasofaríngeas/complicaciones , Neoplasias Nasofaríngeas/patología , Papillomaviridae , Infecciones por Papillomavirus/complicaciones , Adolescente , Adulto , Anciano , Carcinoma de Células Escamosas/complicaciones , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/virología , Niño , Femenino , Humanos , India , Masculino , Persona de Mediana Edad , Neoplasias Nasofaríngeas/virología , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/virología
20.
Integr Cancer Ther ; 13(1): 68-78, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23729467

RESUMEN

Emerging trends for cancer chemotherapy show promising developments with the better understanding of molecules delivering more potent and powerful capabilities. But these are severely limited because of increased side effects and higher probability of tumor recurrence. In this scenario, putative exploration of the indigenous and untapped resources modulating immune system to deliver adequate but potent chemopreventive effects appeals considerable interest. However, these require rigorous scientific validation with regard to potency compared with the existing drugs. Aegle marmelos (Linnaeus) Correa (family Rutaceae), a plant component of polyherbal formulation, Indukantha Ghritha, is known for its widespread medicinal values. But the chemopreventive potential has not been explored in comparison to existing anticancer agents. Our attempt contributes the scientific evidence for beneficial immunoprophylactic and antitumor functions in mice challenged with ascites tumors, Dalton's lymphoma ascites, and Ehrlich's ascites carcinoma either alone or in combination with cyclophosphamide and 5-fluorouracil. Specifically, the petroleum ether extracts of this plant (AM(PE)) prophylactically activated a cascade of host defense mechanisms by stimulating or restoring total white blood cell count, macrophage phagocytosis, hematopoiesis, lymphocyte proliferation and functions (CD4+ and CD8+) either naturally or under conditions of impaired immunity like in ascites tumor or during standard agent chemotherapy. Overall, AM(PE) also elicited strong antitumor effects by increasing median survival time and life span, while reducing murine ascites tumor volume and viable tumor counts on par with cyclophosphamide and 5-fluorouracil especially when administered prophylactically. This study also identified 2 putative components, xanthorrhizol and marmelosin, which could be imparting the immunoprophylactic and antitumor effects in transplantable tumor models. Thus, our attempts provide sufficient proof to warrant further to test this drug in higher animal models or in patients with high risk for tumor recurrence and/or immunocompromised diseases.


Asunto(s)
Aegle , Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias/prevención & control , Preparaciones de Plantas/uso terapéutico , Animales , Carcinoma de Ehrlich/patología , Carcinoma de Ehrlich/prevención & control , Quimioprevención/métodos , Evaluación Preclínica de Medicamentos , Femenino , Masculino , Ratones , Ratones Endogámicos BALB C , Trasplante de Neoplasias , Neoplasias/patología , Fitoterapia , Resultado del Tratamiento
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