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1.
Langmuir ; 35(17): 5702-5710, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-30920224

RESUMO

We present a dynamic mean field theory (DMFT) and nonequilibrium dual control volume grand canonical molecular dynamics (GCMD) simulation study of steady-state fluid transport in slit-shaped mesopores under an applied chemical potential gradient. The main focus is on states where the bulk conditions on one side of the pore would lead to a capillary condensed state in the pore at equilibrium while those on the other side would lead to a vapor state in the pore. This choice of conditions is motivated by certain separation applications in which condensable vapors permeate through mesoporous membranes. Under these circumstances, we have found partially filled states with a liquid-like state at the high chemical potential end of the pore and a vapor-like state at the low chemical potential end. This phenomenon is accompanied by hysteresis. The existence of partially filled states has been hypothesized in previous work but the present paper reveals them as an emergent feature of the systems. We find that predictions of DMFT are in good qualitative agreement with the overall GCMD results. However, the GCMD results demonstrate that the transport is faster through the partially filled pore than through the unfilled pore, a feature not captured by DMFT.

2.
J Chem Phys ; 149(1): 014703, 2018 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-29981543

RESUMO

We use results from grand canonical molecular dynamics (GCMD) to test the predictions from dynamic mean field theory (DMFT) for the pore filling and capillary condensation mechanisms of a fluid confined in slit shaped mesopores. The theory predicts that capillary condensation occurs by a nucleation process in which a liquid bridge forms between the two walls, and the pore is filled via the growth of this bridge. For longer pores, multiple bridging is seen. These mechanisms are confirmed by the molecular dynamics simulations. The primary difference between the theory and simulations lies in the role of fluctuations. DMFT predicts a single nucleation time and location, while in GCMD (and in nature) a distribution of nucleation times and locations is seen.

3.
J Environ Biol ; 36(2): 467-71, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25895272

RESUMO

Field experiments were carried out at Oilseeds Research Area of CCS Haryana Agricultural University, Hisar during rabi, 2008-09 to 2011-12 to find out the possible role of soil application of different micronutrients alone and in combinations in defense to white rust and Alternaria blight diseases in Indian mustard [Brassica juncea (L.) Czern & Coss.]. Among the sole application of micronutrients, minimum disease severity of both white rust (35.0%) and Alternaria blight (31.8%) was observed when S @ 40 kg ha in the form of Gypsum was applied as basal dose in the soil. When Gypsum was supplemented with Borax @10 kg ha(-1) or with ZnSO4 @15 kg ha(-1) the level of tolerance seems to be improved for both the diseases as compared to the sole treatment of each nutrient, i.e., ZnSO4 @ 15 kg/ha, Borax @ 10 kg ha' and Gypsum @ 250 kg ha(-1). Furthermore, minimum disease severity of both white rust (31.3 %) and Alternaria blight (26.3 %) was observed with soil application of ZnSO4 @ 15 kg ha(-1) + Borax @ 10 kg ha(-1) + Gypsum @250 kg ha(-1) as basal dose as compared to the severity of white rust (43.6%) and Alternaria blight (38.6%) in untreated check. Significant increase in seed yield (1612 kg ha(-1)) was also recorded in above mentioned treatment as compared to the yield (1337 kg ha(-1)) in untreated check. These findings will also be helpful in maintaining soil health and minimizing the losses due to both the fungal diseases for eco-friendly sustainability of Indian mustard.


Assuntos
Alternaria/fisiologia , Mostardeira/metabolismo , Doenças das Plantas/microbiologia , Índia
4.
Sci Rep ; 14(1): 22421, 2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39341935

RESUMO

Electronic spins associated with the Nitrogen-Vacancy (NV) center in diamond offer an opportunity to study spin-related phenomena with extremely high sensitivity owing to their high degree of optical polarization. Here, we study both single- and double-quantum transitions (SQT and DQT) in NV centers between spin-mixed states, which arise from magnetic fields that are non-collinear to the NV axis. We demonstrate the amplification of the ESR signal from both these types of transition under laser illumination. We obtain hyperfine-resolved X-band ESR signal as a function of both excitation laser power and misalignment of static magnetic field with the NV axis. This, combined with our analysis using a seven-level model that incorporates thermal polarization and double quantum relaxation, allows us to comprehensively analyze the polarization of NV spins under off-axis fields. Such detailed understanding of spin-mixed states in NV centers under photo-excitation can help greatly in realizing NV-diamond platform's potential in sensing correlated magnets and biological samples, as well as other emerging applications, such as masing and nuclear hyperpolarization.

5.
Trop Gastroenterol ; 32(2): 122-7, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21922876

RESUMO

BACKGROUND: Colorectal cancer is rare in younger age group. Most cases occur in the second decade of life and are clinically aggressive. The prognosis of these patients is generally poor. This is a retrospective study in which data of Indian patients was compared to standard literature. METHODS: Data on 32 young patients with colorectal cancer between ages of 10-25 years treated between January 2000 and December 2006 was reviewed. Clinical presentation, natural history and response to therapy were evaluated. RESULTS: Studied cases comprised 9.9% of the total number of colorectal cancer patients. The median age of presentation was 21.5 years. Four-fifths of the cases presented in late stage. Nodal involvement was seen in 38% cases and metastatic disease in 12% cases. The rectum was the most commonly involved site. A majority of the patients presented with pain (81%), altered bowel habits (72%) and bleeding per rectum (78%). Surgery was done in 16 cases; radiotherapy in 16 patients; while chemotherapy was used in 19 cases. Responses at completion of treatment were seen in 28% cases; while 1 year post treatment only 12% cases were alive and only 6% at 2 years. CONCLUSIONS: Colorectal cancer in younger age is rare and a high level of suspicion is necessary to diagnose it at an early and curable stage. Rectal bleeding therefore should not be ignored but evaluated further with at least a digital rectal examination and a sigmoidoscopy. Failure to do so results in late presentation with consequent dismal survival rates.


Assuntos
Neoplasias Colorretais/epidemiologia , Adolescente , Adulto , Criança , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Feminino , Humanos , Índia/epidemiologia , Masculino , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
6.
Emerg Infect Dis ; 15(2): 295-8, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19193277

RESUMO

An outbreak of viral encephalitis occurred in northern India in 2006. Attempts to identify an etiologic agent in cerebrospinal fluid by using reverse transcription-PCR showed positivity to enterovirus (EV) in 66 (21.6%) of 306 patients. Sequencing and phylogenetic analyses of PCR products from 59 (89.3%) of 66 specimens showed similarity with EV-89 and EV-76 sequences.


Assuntos
Líquido Cefalorraquidiano/virologia , Surtos de Doenças , Encefalite Viral , Enterovirus , Doença Aguda , Adolescente , Animais , Linhagem Celular , Linhagem Celular Tumoral , Criança , Pré-Escolar , Cricetinae , Encefalite Viral/diagnóstico , Encefalite Viral/epidemiologia , Encefalite Viral/virologia , Enterovirus/classificação , Enterovirus/genética , Enterovirus/isolamento & purificação , Infecções por Enterovirus/diagnóstico , Infecções por Enterovirus/epidemiologia , Infecções por Enterovirus/virologia , Humanos , Índia/epidemiologia , Lactente , Recém-Nascido , Filogenia , RNA Viral/análise , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA
7.
Trop Gastroenterol ; 29(2): 112-3, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18972776

RESUMO

Krukenberg tumour (KT) is a metastatic ovarian tumour with primary usually seen in the gastrointestinal tract. Here we report the case of a 50-year old menopausal patient with gastric tumour presenting with solitary metastasis to the ovary within 5 months of primary gastric surgery, for which total abdominal hysterectomy with bilateral salpingo-oophorectomy was done. This case stresses the urgent need for early detection and surveillance of treatable tumours metastasising to the ovary.


Assuntos
Tumor de Krukenberg/secundário , Neoplasias Ovarianas/secundário , Neoplasias Gástricas/patologia , Feminino , Humanos , Tumor de Krukenberg/diagnóstico , Tumor de Krukenberg/cirurgia , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/cirurgia
8.
Indian J Pathol Microbiol ; 51(3): 386-8, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18723965

RESUMO

Primitive neuroectodermal tumors (PNETs) are malignant proliferations of small, undifferentiated neuroectodermal cells occurring mainly in children and share the same reciprocal translocation between chromosomes 11 and 22 and the same patterns of biochemical and oncogene expression as osseus and extraosseus Ewing's sarcoma. Some PNETs occur in the brain, while others (the peripheral PNETs) occur in sites outside the brain, such as in the extremities, pelvis and the chest wall. They mostly originate in the chest, pelvis and retroperitoneum; in rare cases, occurrence in the head and neck area has also been seen. We present a rare case of primitive neuroectodermal tumor arising in the prostate gland in a 25-year-old male. To the best of our knowledge, this is the first documentation of a primary peripheral primitive neuroectodermal tumor in the prostate gland of any patient from India and rarely reported in English literature.


Assuntos
Tumores Neuroectodérmicos Primitivos/diagnóstico , Tumores Neuroectodérmicos Primitivos/patologia , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Adulto , Biópsia por Agulha , Humanos , Índia , Masculino
9.
Indian Phytopathol ; 71(3): 407-413, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30595619

RESUMO

Fourteen isolates of Sclerotinia sclerotiorum were collected from different locations of mustard growing regions of India and were studied for cultural, morphological and molecular variability at CCS HAU, Hisar. Variability was observed for colony colour, type of growth, diameter of mycelial growth, sclerotia initiation, number and pattern of sclerotia formation among the isolates. Mycelial growth and sclerotia initiation were faster in Bhiwani isolate as compared to others. Bhiwani isolate was found to be the most diverse and had least similarity with Chhanibari isolate on the basis of molecular variability. Hence, morphological and cultural variability observed in the present investigation is by and large strongly correlated to molecular marker based variability.

10.
J Tradit Complement Med ; 8(4): 506-514, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30302331

RESUMO

In view of the overall health impact of NIDDM, inventers understand the necessity of improving glycemic control in adults with type 2 diabetes. BGR-34 provides an effective treatment option for adults with type 2 diabetes who have been inadequately controlled on lifestyle with or without other oral hypoglycemic agents (OHGAs) such as metformin, sulfonylurea, or a glitazones. BGR-34 is an appropriate option to consider for addition to a managed care drug formulary. Treatment with BGR-34 produced clinically relevant and statistically significant reductions in all three key measures of glucose control studied -FPG, PPBG and HbA1c- when compared with placebo. BGR-34, showed the promising result with respect to glycemic parameters in NIDDM patient with a significant reduction in fasting blood sugar by 34.3%, postprandial blood sugar 35.5% & glycosylated haemoglobin by 20.31% as compared to placebo group showing a reduction by 13.2%, 10.9% & 10.87% respectively. The trial has also been registered to CTRI, India. This study has been registered in the clinical trial registry-India.

11.
South Asian J Cancer ; 7(2): 137-141, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29721481

RESUMO

Metastatic breast cancer (MBC) is cancer that has spread from the breast to another part of the body or has come back in another distant location. Treatment options for MBC depend on several factors. One of these factors is the levels of hormone receptors (HRs) in the tumor. Cancers with high levels of HRs, called HR-positive, use the hormones estrogen and progesterone to grow and spread. Hormonal therapy is a type of treatment specifically for HR-positive breast cancer. This expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at these practical consensus recommendations in regards with the use of hormonal therapy and the management of HR-positive MBC for the benefit of community oncologists.

12.
South Asian J Cancer ; 7(2): 146-150, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29721483

RESUMO

Metastatic breast cancer (MBC) is cancer that has spread from the breast to another part of the body or has come back in another distant location. Treatment options for MBC depend on several factors, including where the cancer has spread, the patient's overall health, and the levels of hormone receptors and HER2 in the tumour. Over-expression of HER2 is generally considered to be a negative prognostic feature because it accompanies an increase in breast cancer mortality. However, the development of agents that specifically target HER2 has improved the management of patients with these tumours.[7],[8],[9],[10] This expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at these practical consensus recommendations in regards with the use of these agents and the management of HER2 positive MBC for the benefit of community oncologists.

13.
Mol Cell Biol ; 11(6): 3339-47, 1991 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-2038336

RESUMO

In Dictyostelium discoideum, there is a group of genes that are expressed following starvation and when exponentially growing cells reach high densities. We have examined the expression of one of these genes, alpha-mannosidase. Using an alpha-mannosidase cDNA probe in Northern (RNA) blot analysis, we have shown that the previously observed increase in alpha-mannosidase enzyme-specific activity during development is due to an increase in the levels of alpha-mannosidase mRNA. mRNA levels reach a maximum by 8 h of development and then begin to decline by 14 to 22 h. Using nuclear run-on analysis, we have found that this gene is regulated at the level of transcription. We also examined the effects of cell-cell contacts, cyclic AMP levels, and protein synthesis on expression of this gene and found that they were not critical in regulating its expression. However, cell density did play a major role in the expression of alpha-mannosidase. High cell density or the presence of buffer conditioned by high-density cells was sufficient to induce expression of alpha-mannosidase, indicating that this is one of the prestarvation response genes. Finally, the alpha-mannosidase gene was not expressed in aggregation-negative mutant strain HMW 404.


Assuntos
Dictyostelium/genética , Regulação Enzimológica da Expressão Gênica , Regulação Fúngica da Expressão Gênica , Genes Fúngicos , Manosidases/genética , Transcrição Gênica , Northern Blotting , Sondas de DNA , Dictyostelium/enzimologia , Dictyostelium/crescimento & desenvolvimento , Cinética , RNA Fúngico/genética , RNA Fúngico/isolamento & purificação , RNA Mensageiro/genética , RNA Mensageiro/isolamento & purificação , Fatores de Tempo , alfa-Manosidase
15.
Indian J Cancer ; 54(1): 308-312, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29199711

RESUMO

Cancer is hypercoagulable state. Patients with cancer are at high risk to develop venous thromboembolism (VTE). Relative risk of developing VTE is approximately seven times higher in patients with active cancer. The incidence of occult malignancy is 7%-12% in patients with idiopathic deep vein thrombosis (DVT). However, little research has been focused on cancer with thromboembolism. Lowmolecularweight heparin most frequently used pharmacologic agents as recommended by established guidelines. The aim was to evaluate the magnitude of problem in cancer patients and treatment option as per established guidelines. EMBASE, MEDLINE, and PubMed search of the literature were done to evaluate the association of DVT with various malignancy, magnitude of problem, approach, and various guidelines for the management of DVT. References of all publication were also searched to enrich this article for recent update. Thromboprophylaxis in cancer patient is gray zone area. This need lot of investigational work to find highrisk patients who would benefit from primary thromboprophylaxis.


Assuntos
Neoplasias/patologia , Tromboembolia Venosa/patologia , Trombose Venosa/patologia , Heparina/uso terapêutico , Humanos , Índia/epidemiologia , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologia , Fatores de Risco , Tromboembolia Venosa/complicações , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/epidemiologia , Trombose Venosa/complicações , Trombose Venosa/epidemiologia
16.
J Natl Cancer Inst ; 92(16): 1303-7, 2000 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-10944551

RESUMO

BACKGROUND: Retinoic acid plays an important role in lung development and differentiation, acting primarily via nuclear receptors encoded by the retinoic acid receptor-beta (RARbeta) gene. Because receptor isoforms RARbeta2 and RARbeta4 are repressed in human lung cancers, we investigated whether methylation of their promoter, P2, might lead to silencing of the RARbeta gene in human lung tumors and cell lines. METHODS: Methylation of the P2 promoter from small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) cell lines and tumor samples was analyzed by the methylation-specific polymerase chain reaction (PCR). Expression of RARbeta2 and RARbeta4 was analyzed by reverse transcription-PCR. Loss of heterozygosity (LOH) was analyzed by PCR amplification followed by electrophoretic separation of PCR products. Statistical differences were analyzed by Fisher's exact test with continuity correction. RESULTS: The P2 promoter was methylated in 72% (63 of 87) of SCLC and in 41% (52 of 127) of NSCLC tumors and cell lines, and the difference was statistically significant (two-sided P:<.001). By contrast, in 57 of 58 control samples, we observed only the unmethylated form of the gene. Four tumor cell lines with unmethylated promoter regions expressed both RARbeta2 and RARbeta4. Four tumor lines with methylated promoter regions lacked expression of these isoforms, but demethylation by exposure to 5-aza-2'-deoxycytidine restored their expression. LOH at chromosome 3p24 was observed in 100% (13 of 13) of SCLC lines and 67% (12 of 18) of NSCLC cell lines, and the difference was statistically significant (two-sided P: =.028). CONCLUSIONS: Methylation of the RARbeta P2 promoter is one mechanism that silences RARbeta2 and RARbeta4 expression in many lung cancers, particularly SCLC. Chemical demethylation is a potential approach to lung cancer therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma de Células Pequenas/metabolismo , Perda de Heterozigosidade , Neoplasias Pulmonares/metabolismo , Regiões Promotoras Genéticas , Receptores do Ácido Retinoico/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Pequenas/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Metilação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas
17.
Diabetes ; 33(6): 586-9, 1984 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-6327438

RESUMO

The level of superoxide anion was found to be significantly elevated in polymorphonuclear leukocytes (PMNL) from diabetic subjects as compared with those from normal subjects. This elevation was attributed to the significant reduction in the activities of both cytoplasmic and mitochondrial superoxide dismutase (SOD), the effect being more pronounced in the cytoplasmic fraction. Although the content of copper decreased considerably in the diabetic PMNL, the decrease in the zinc content was less significant, with an insignificant alteration in the content of manganese. PMNL obtained from insulin-treated diabetic patients showed considerable alleviation of SOD levels. The implication of these results are discussed herein.


Assuntos
Diabetes Mellitus/enzimologia , Neutrófilos/enzimologia , Superóxido Dismutase/sangue , Adulto , Cobre/sangue , Humanos , Masculino , Manganês/sangue , Pessoa de Meia-Idade , Superóxidos/sangue , Zinco/sangue
18.
Mech Dev ; 36(3): 173-82, 1992 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-1315152

RESUMO

Throughout growth, Dictyostelium cells continuously produce an autocrine factor, PSF, that accumulates in proportion to cell density. Production of PSF declines rapidly when cells are shifted to starvation conditions, and the properties of PSF are distinct from those of regulatory factors produced by starving cells. During late exponential growth, PSF induces expression of several early developmental genes, including those for proteins important in cAMP signaling and cell aggregation. Examples are the aggregation stage cAMP receptor (cAR1), the aggregation-specific form of cyclic nucleotide phosphodiesterase, and gp24 (contact sites B). Through PSF, growing cells detect environmental conditions (cell number high, food approaching depletion) that are appropriate for production of the gene products needed to initiate aggregation and development.


Assuntos
Dictyostelium/genética , Regulação Fúngica da Expressão Gênica , Substâncias de Crescimento/genética , Animais , Northern Blotting , Agregação Celular , Comunicação Celular , Diferenciação Celular/genética , Células Cultivadas/efeitos dos fármacos , Cicloeximida/farmacologia , Endopeptidases/farmacologia , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Substâncias de Crescimento/metabolismo , Diester Fosfórico Hidrolases/análise , Diester Fosfórico Hidrolases/genética , Receptores de AMP Cíclico/análise , Receptores de AMP Cíclico/genética
19.
Clin Cancer Res ; 7(3): 584-9, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11297252

RESUMO

We studied the pattern of aberrant methylation during the multistage pathogenesis of cervical cancers. We analyzed a total of 73 patient samples and 10 cervical cancer cell lines. In addition, tissue samples [peripheral blood lymphocytes (n = 10) and buccal epithelial cells (n = 12)] were obtained from 22 healthy volunteers. On the basis of the results of preliminary analysis, the cervical samples were grouped into three categories: (a) nondysplasia/low-grade cervical intraepithelial neoplasia (CIN; n = 37); (b) high-grade CIN (n = 17); and (c) invasive cancer (n = 19). The methylation status of six genes was determined (p16, RARbeta, FHIT, GSTP1, MGMT, and hMLH1). Our main findings are as follows: (a) methylation was completely absent in control tissues; (b) the frequencies of methylation for all of the genes except hMLH1 were >20% in cervical cancers; (c) aberrant methylation commenced early during multistage pathogenesis and methylation of at least one gene was noted in 30% of the nondysplasia/low-grade CIN group; (d) an increasing trend for methylation was seen with increasing pathological change; (e) methylation of RARbeta and GSTP1 were early events, p16 and MGMT methylation were intermediate events, and FHIT methylation was a late, tumor-associated event; and (f) methylation occurred independently of other risk factors including papillomavirus infection, smoking history, or hormone use. Although our findings need to be extended to a larger series, they suggest that the pattern of aberrant methylation in women with or without dysplasia may help identify subgroups at increased risk for histological progression or cancer development.


Assuntos
Hidrolases Anidrido Ácido , Metilação de DNA , Proteínas de Neoplasias , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Colo do Útero/metabolismo , Feminino , Genes p16/genética , Glutationa S-Transferase pi , Glutationa Transferase/metabolismo , Humanos , Isoenzimas/metabolismo , Metilação , Proteínas/metabolismo , Receptores do Ácido Retinoico/genética , Células Tumorais Cultivadas
20.
Clin Cancer Res ; 7(7): 1998-2004, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11448917

RESUMO

The adenomatous polyposis coli (APC) gene is a tumor suppressor gene associated with both familial and sporadic cancer. Despite high rates of allelic loss in lung and breast cancers, point mutations of the APC gene are infrequent in these cancer types. Aberrant methylation of the APC promoter 1A occurs in some colorectal and gastric malignancies, and we investigated whether the same mechanism occurs in lung and breast cancers. The methylation status of the APC gene promoter 1A was analyzed in 77 breast, 50 small cell (SCLC), and 106 non-small cell (NSCLC) lung cancer tumors and cell lines and in 68 nonmalignant tissues by methylation-specific PCR. Expression of the APC promoter 1A transcript was examined in a subset of cell lines by reverse transcription-PCR, and loss of heterozygosity at the gene locus was analyzed by the use of 12 microsatellite and polymorphic markers. Statistical tests were two-sided. Promoter 1A was methylated in 34 of 77 breast cancer tumors and cell lines (44%), in 56 of 106 NSCLC tumors and cell lines (53%), in 13 of 50 SCLC cell lines (26%), and in 3 of 68 nonmalignant samples (4%). Most cell lines tested contained the unmethylated or methylated form exclusively. In 27 cell lines tested, there was complete concordance between promoter methylation and silencing of its transcript. Demethylation with 5-aza-2'-deoxycytidine treatment restored transcript 1A expression in all eight methylated cell lines tested. Loss of heterozygosity at the APC locus was observed in 85% of SCLCs, 83% of NSCLCs, and 63% of breast cancer cell lines. The frequency of methylation in breast cancers increased with tumor stage and size. In summary, aberrant methylation of the 1A promoter of the APC gene and loss of its specific transcript is frequently present in breast and NSCLC cancers and cell lines and, to a lesser extent, in SCLC cell lines. Our findings may be of biological and clinical importance.


Assuntos
Neoplasias da Mama/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Proteínas do Citoesqueleto/genética , Metilação de DNA , Neoplasias Pulmonares/genética , Regiões Promotoras Genéticas/genética , Proteína da Polipose Adenomatosa do Colo , Processamento Alternativo , Neoplasias da Mama/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Cromossomos Humanos Par 5/genética , DNA de Neoplasias/genética , DNA de Neoplasias/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Perda de Heterozigosidade , Neoplasias Pulmonares/patologia , Repetições de Microssatélites , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas
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