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1.
Indian J Surg Oncol ; 12(2): 272-278, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34295070

RESUMO

The ACOSOG Z0011 study, heralded as a "practice changing" trial, suggested that women with T1-2 breast cancer with 1-2 SLN+, undergoing breast conservation therapy, need not be offered further ALND. However, whether these results are applicable to all women in the Indian setting, it remains debatable. A retrospective audit of all cN0 operated from 2013 to 2018 was conducted. We analyzed the percentage of additional LN positive (LN+) in the ALND group and compared it to the ACOZOG Z11 trial. Of the 2350 cN0 with EBC who underwent LAS, 687 (29%) had positive lymph nodes on final histopathology. Five hundred ninety-seven (86.9%) patients had 1-2 LN+, 40 (5.8%) patients had 3 LN+, and 50 (7.3%) had 4 or more nodes positive. Demographic features in the ACOSOG Z11 are different from those in our study, looking at ACOZOG Z11 versus our cohort-median pT 1.7 cm versus 3 cm, 45% micrometastasis versus 99.16% macrometastasis, and 28-30% grade 3 tumors versus 73.7%. In our cohort 31.82% of the 1-2 LN positive had additional LN+ on ALND. Keeping in mind the difference in clinicopathological features between our cohort and that of ACOZOG Z0011 and that 31.82% of women had additional LN+ on ALND, it may not be appropriate to apply the results of the ACOSOG Z0011 trial directly to our general population. Possibly, only a select subset of patients who match the trial population of the ACOSOG Z11 could be offered observation of the axilla and validated nomograms can be used to identify high-risk patients.

2.
J Exp Clin Cancer Res ; 39(1): 78, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375866

RESUMO

The majority of high-risk neuroblastomas can be divided into three distinct molecular subgroups defined by the presence of MYCN amplification, upstream TERT rearrangements or alternative lengthening of telomeres (ALT). The common defining feature of all three subgroups is altered telomere maintenance; MYCN amplification and upstream TERT rearrangements drive high levels of telomerase expression whereas ALT is a telomerase independent telomere maintenance mechanism. As all three telomere maintenance mechanisms are independently associated with poor outcomes, the development of strategies to selectively target either telomerase expressing or ALT cells holds great promise as a therapeutic approach that is applicable to the majority of children with aggressive disease.Here we summarise the biology of telomere maintenance and the molecular drivers of aggressive neuroblastoma before describing the most promising therapeutic strategies to target both telomerase expressing and ALT cancers. For telomerase-expressing neuroblastoma the most promising targeted agent to date is 6-thio-2'-deoxyguanosine, however clinical development of this agent is required. In osteosarcoma cell lines with ALT, selective sensitivity to ATR inhibition has been reported. However, we present data showing that in fact ALT neuroblastoma cells are more resistant to the clinical ATR inhibitor AZD6738 compared to other neuroblastoma subtypes. More recently a number of additional candidate compounds have been shown to show selectivity for ALT cancers, such as Tetra-Pt (bpy), a compound targeting the telomeric G-quadruplex and pifithrin-α, a putative p53 inhibitor. Further pre-clinical evaluation of these compounds in neuroblastoma models is warranted.In summary, telomere maintenance targeting strategies offer a significant opportunity to develop effective new therapies, applicable to a large proportion of children with high-risk neuroblastoma. In parallel to clinical development, more pre-clinical research specifically for neuroblastoma is urgently needed, if we are to improve survival for this common poor outcome tumour of childhood.


Assuntos
Neuroblastoma/terapia , Telômero/fisiologia , Linhagem Celular Tumoral , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Neuroblastoma/tratamento farmacológico , Neuroblastoma/genética , Telômero/efeitos dos fármacos , Telômero/genética , Telômero/metabolismo
3.
Indian J Cancer ; 54(1): 352-357, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29199721

RESUMO

BACKGROUND: Role of postmastectomy radiotherapy (PMRT) in early breast cancer with 1-3 positive axillary nodes is still controversial. Hence, there is a need to identify subgroup of patients who have sufficiently high risk of disease recurrence to benefit from PMRT. AIM: The aim is to evaluate clinical outcomes of patients postmastectomy having pathological T1-T2 tumors with 1-3 positive axillary lymph nodes (LNs) treated with adjuvant systemic therapy and develop a predictive nomogram. MATERIALS AND METHODS: Data collected retrospectively from eligible patients from 2005 to 2011. Kaplan-Meier survival analysis was used for all time-to-event analysis. Various known clinical and pathological risk factors were correlated with outcome using uni- and multi-variable analysis in SPSS version 21. All comparisons were two-tailed and P < 0.05 were considered statistically significant. The nomogram to predict the risk of loco-regional control (LRC) was developed using least absolute shrinkage and selection operator shrinkage model in hdnom.io software. RESULTS: 38/242 (15.7%) patients had recurrent disease at loco-regional (10 patients), distant sites (22 patients) and simultaneous loco-regional and distant sites (6 patients) at a median follow-up 59.5 (range 4-133) months. Five years estimate of LRC, distant disease-free survival (DFS), DFS, cause-specific survival and overall survival was 87.8%, 85.4%, 84.2%, 93.1%, and 91.5%, respectively. Pathological tumor size, margin status, LN ratio as continuous variables and grade and triple negative breast cancer status as categorical variables were the risk factors included in the model for building nomogram. CONCLUSION: The nomogram developed based on institutional data can be a valuable tool in guiding adjuvant PMRT depending on the risk of 5 years loco-regional recurrence.


Assuntos
Neoplasias da Mama/cirurgia , Metástase Linfática/radioterapia , Recidiva Local de Neoplasia/cirurgia , Radioterapia Adjuvante , Adulto , Idoso , Axila/patologia , Axila/efeitos da radiação , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Linfonodos/patologia , Linfonodos/efeitos da radiação , Linfonodos/cirurgia , Metástase Linfática/patologia , Mastectomia/efeitos adversos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Nomogramas
4.
Ann Oncol ; 28(9): 2225-2232, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28911092

RESUMO

BACKGROUND: Recent breast cancer treatment guidelines recommend that higher-risk premenopausal patients should receive ovarian function suppression (OFS) as part of adjuvant endocrine therapy. If chemotherapy is also given, it is uncertain whether to select concurrent or sequential OFS initiation. DESIGN AND METHODS: We analyzed 1872 patients enrolled in the randomized phase III TEXT and SOFT trials who received adjuvant chemotherapy for hormone receptor-positive, HER2-negative breast cancer and upon randomization to an OFS-containing adjuvant endocrine therapy, initiated gonadotropin-releasing-hormone-agonist triptorelin. Breast cancer-free interval (BCFI) was compared between patients who received OFS concurrently with chemotherapy in TEXT (n = 1242) versus sequentially post-chemotherapy in SOFT (n = 630). Because timing of trial enrollment relative to adjuvant chemotherapy differed, we implemented landmark analysis re-defining BCFI beginning 1 year after final dose of chemotherapy (median, 15.5 and 8.1 months from enrollment to landmark in TEXT and SOFT, respectively). As a non-randomized treatment comparison, we implemented comparative-effectiveness propensity score methodology with weighted Cox modeling. RESULTS: Distributions of several clinico-pathologic characteristics differed between groups. Patients who were premenopausal post-chemotherapy in SOFT were younger on average. The median duration of adjuvant chemotherapy was 18 weeks in both groups. There were 231 (12%) BC events after post-landmark median follow-up of about 5 years. Concurrent use of triptorelin with chemotherapy was not associated with a significant difference in post-landmark BCFI compared with sequential triptorelin post-chemotherapy, either in the overall population (HR = 1.11, 95% CI 0.72-1.72; P = 0.72; 4-year BCFI 89% in both groups), or in the subgroup of 692 women <40 years at diagnosis (HR = 1.13, 95% CI 0.69-1.84) who are less likely to develop chemotherapy-induced amenorrhea. CONCLUSION: Based on comparative-effectiveness modeling of TEXT and SOFT after about 5 years median follow-up, with limited statistical power especially for the subgroup <40 years, neither detrimental nor beneficial effect of concurrent administration of OFS with chemotherapy on the efficacy of adjuvant therapy that includes chemotherapy was detected. CLINICALTRIALS.GOV: NCT00066690 and NCT00066703.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Ovário/efeitos dos fármacos , Pré-Menopausa , Adulto , Neoplasias da Mama/fisiopatologia , Feminino , Humanos , Pessoa de Meia-Idade , Ovário/fisiopatologia
5.
JNMA J Nepal Med Assoc ; 54(201): 8-16, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27935905

RESUMO

INTRODUCTION: An outbreak of acute gastroenteritis had occurred in Rajpara village of Bhavnagar district. The objective of this study was to find out the socio-demographic, epidemiological and environmental determinants of this outbreak. METHODS: A case-control study was conducted in Rajpara village among 238 cases of acute gastroenteritis and an equal number of controls in January 2015. Multiple logistic regression was used for identifying the variables independently predicting acute gastroenteritis. RESULTS: Upper socio-economic status, occupation requiring travel outside village, source of drinking water from well of 'new' Rajpara village, change in taste of water, use of chlorine tablets, travel outside village in last week, another family member affected with acute gastroenteritis, using common utensil for hand washing, hand washing before eating, ate food from outside in last week, having sanitary latrine at house, waste disposal in a common dump (instead of at house), waste accumulation around house and flies inside house were significantly associated with occurrence of acute gastroenteritis. On multiple logistic regression, change in taste of water (P<0.001), waste disposal in a common dump (P=0.012), another family member been affected (P<0.001), waste accumulation around house (P<0.001), higher socio-economic status (P=0.002) and eating outside food (P=0.011) made a significant contribution to prediction. CONCLUSIONS: Socio-demographic factors (higher socio-economic status), epidemiological correlates (change in taste of water, another family member been affected with acute gastroenteritis and eating outside food) and environmental determinants (waste disposal in a common dump and waste accumulation around house) significantly determines the occurrence of cases of acute gastroenteritis.


Assuntos
Surtos de Doenças/estatística & dados numéricos , Gastroenterite/epidemiologia , Doença Aguda , Estudos de Casos e Controles , Gastroenterite/etiologia , Humanos , Higiene , Índia/epidemiologia , Ocupações , Análise de Regressão , Fatores Socioeconômicos , Gerenciamento de Resíduos , Abastecimento de Água
6.
Eur J Cancer ; 66: 153-61, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27573429

RESUMO

BACKGROUND: Current evidence suggests that the relationship between obesity and breast cancer (BC) risk may vary between ethnic groups. METHODS: A total of 1633 BC cases and 1504 controls were enrolled in hospital-based case-control study in Mumbai, India, from 2009 to 2013. Along with detailed questionnaire, we collected anthropometric measurements on all participants. We used unconditional logistic regression models to estimate odds ratios (ORs) and 95% confidence interval (CI) for BC risk associated with anthropometry measurements, stratified on tumour subtype and menopausal status. RESULTS: Waist-to-hip ratio (WHR) of ≥0.95 was strongly associated with risk of BC compared to WHR ≤0.84 in both premenopausal (OR = 4.3; 95% CI: 2.9-6.3) and postmenopausal women (OR = 3.4; 95% CI: 2.4-4.8) after adjustment for body mass index (BMI). Premenopausal women with a BMI ≥30 were at lower risk compared to women with normal BMI (OR = 0.5; 95% CI: 0.4-0.8). A similar protective effect was observed in women who were postmenopausal for <10 years (OR = 0.6; 95% CI: 0.4-0.9) but not in women who were postmenopausal for ≥10 years (OR = 1.8; 95% CI: 1.1-3.3). Overweight and obese women (BMI: 25-29.9 and ≥ 30 kg/m(2), respectively) were at increased BC risk irrespective of menopausal status if their WHR ≥0.95. Central obesity (measured in terms of WC and WHR) increased the risk of both premenopausal and postmenopausal BCs irrespective of hormone receptor (HR) status. CONCLUSIONS: Central obesity appears to be a key risk factor for BC irrespective of menopausal or HR status in Indian women with no history of hormone replacement therapy.


Assuntos
Menopausa/etnologia , Obesidade Abdominal/complicações , Adulto , Idoso , Índice de Massa Corporal , Neoplasias da Mama/etnologia , Neoplasias da Mama/etiologia , Estudos de Casos e Controles , Feminino , Humanos , Índia/etnologia , Pessoa de Meia-Idade , Obesidade Abdominal/etnologia , Receptor ErbB-2/fisiologia , Receptores de Estrogênio/fisiologia , Receptores de Progesterona/fisiologia , Fatores de Risco , Circunferência da Cintura/etnologia , Adulto Jovem
8.
Indian J Surg ; 77(Suppl 1): 79-80, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25972653

RESUMO

Femoral hernias are elusive conditions that, despite having life-threatening complications, are often undiagnosed in asymptomatic patients. They are less common than inguinal hernias and occur more frequently in females [Purushotham et al. (2014) J Evol Med Dent Sci 3(05):1160-1163]. In the first place, femoral hernia in a male patient is itself, a very rare clinical presentation, let alone complications like obstruction or strangulation in the second place. Thus, despite the fact that femoral hernias account for only 2-4 % of all groin hernias, their timely and correct diagnosis is vital due to the increased mortality associated with emergency surgery for their complications [Arkoulis et al. (2012) Ox J Med, J Surg Case Rep 2012(6):6]. This, however, is not always easy, where mortality has been found to be tenfold. Here, we present a case of right-sided obstructed femoral hernia of Richter's variety in a male of 52 years of age.

9.
Physiotherapy ; 101(1): 82-7, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25125386

RESUMO

OBJECTIVE: To compare sensitivity of pathology on imaging between referrals from primary care, physiotherapists, spinal surgeons and other secondary care providers. DESIGN AND SETTING: A retrospective review of 200 consecutive magnetic resonance imaging (MRI) scans of patients' first presentations to radiology for MR lumbar scanning at a tertiary orthopaedic centre. A scan report was defined as positive if there was any evidence of neural compromise. Fisher's exact 2×2 contingency analyses were performed. RESULTS: Eighty-seven (44%) scans were positive and 113 (57%) were negative. Forty-four percent of scans requested by general practitioners (GPs) were reported as positive compared with 57% of scans requested by physiotherapists. Only 40% and 20% of scans requested by specialist spinal surgeons and non-spinal team secondary care providers were positive, respectively. Physiotherapist referrals for MRI lumbar spine scans were significantly more likely to be positive compared with GPs (P=0.05), spinal surgeons (P=0.03) and others (P=0.004). CONCLUSION: When appropriate, referrals via the extended physiotherapy service should be encouraged, rather than referrals directly from GPs. With appropriate training and in the appropriate clinical context, extended physiotherapy services could include inpatients and could accept outpatient referrals from other secondary care providers and not just from GPs; this would improve efficiency and reduce the workload of the radiology department and the spinal surgical unit.


Assuntos
Procedimentos Clínicos/organização & administração , Dor Lombar/diagnóstico , Vértebras Lombares/patologia , Imageamento por Ressonância Magnética/estatística & dados numéricos , Encaminhamento e Consulta/estatística & dados numéricos , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Degeneração do Disco Intervertebral/diagnóstico , Degeneração do Disco Intervertebral/reabilitação , Dor Lombar/reabilitação , Masculino , Pessoa de Meia-Idade , Avaliação das Necessidades , Neurocirurgia/estatística & dados numéricos , Avaliação de Resultados em Cuidados de Saúde , Fisioterapeutas/estatística & dados numéricos , Médicos de Atenção Primária/estatística & dados numéricos , Estudos Retrospectivos , Atenção Secundária à Saúde/estatística & dados numéricos , Reino Unido , Listas de Espera
10.
Vet World ; 8(5): 561-6, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-27047135

RESUMO

AIM: The aim was to study the seroprevalence and efficacy of the different serological tests used for detection of antibody against Brucella species in small ruminants of Banaskantha district of North-Gujarat. MATERIALS AND METHODS: Total 1000 serum samples comprising of 485 from sheep and 515 from goat tested for detection of antibodies against the Brucella species by three different serological tests viz., Rose bengal plate test (RBPT), Standard tube agglutination test (STAT), and Indirect Enzyme-linked immunosorbent assay (I-ELISA). RESULTS: The seroprevalence of brucellosis in small ruminants was 11.30%, 11.10%, and 8.80% by RBPT, STAT, and I-ELISA, respectively. The seroprevalence of brucellosis was found to be higher in sheep than goats. The sensitivity of RBPT was found slight more than STAT, but the specificity of both tests was same. In this study, the overall agreement of RBPT and STAT with I-ELISA was found 92.50% and 92.30% in small ruminants, respectively. CONCLUSION: I-ELISA was a better serological test as compared to RBPT and STAT in the sense of sensitivity, specificity, and rapidity and it could be advocated for screening of brucellosis in sheep and goats.

11.
Indian J Pharm Sci ; 76(3): 225-9, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-25035534

RESUMO

High-performance liquid chromatographic and UV spectrophotometric methods were developed and validated for the quantitative determination of pirfenidone, a novel antifibrotic agent used in idiopathic pulmonary fibrosis. Chromatography was carried out by isocratic technique on a reversed-phase C18 Zorbax Eclipse plus column with mobile phase consisting of acetonitrile:water (35:65 %v/v) at flow rate of 0.7 ml/min. The UV spectrophotometric determinations were performed at 317 nm using methanol as a solvent. The proposed methods were validated according to International Conference on Harmonization ICH Q2 (R1) guidelines. The linearity range for pirfenidone was 0.2-5.0 and 3-25 µg/ml for HPLC and UV method, respectively. Both the methods were accurate and precise with recoveries in the range of 98 and 102 % and relative standard deviation <2 %. The developed methods were successfully applied for determination of pirfenidone in tablets.

12.
Indian J Cancer ; 51(1): 73-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24947101

RESUMO

The management of hormone receptor-positive Her2-negative breast cancer patients with advanced or metastatic disease is a common problem in India and other countries in this region. This expert group used data from published literature, practical experience, and opinion of a large group of academic oncologists, to arrive at practical consensus recommendations for use by the community oncologists.


Assuntos
Neoplasias da Mama/terapia , Consenso , Guias de Prática Clínica como Assunto , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Neoplasias da Mama/metabolismo , Terapia Combinada , Gerenciamento Clínico , Feminino , Humanos , Sociedades Médicas
13.
Clin Neurol Neurosurg ; 123: 155-63, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24956545

RESUMO

Refractory pain syndromes often have far reaching effects and are quite a challenge for primary care providers and specialists alike to treat. With the help of site-specific neuromodulation and appropriate patient selection these difficult to treat pain syndromes may be managed. In this article, we focus on supraspinal stimulation (SSS) for treatment of intractable pain and discuss off-label uses of deep brain stimulation (DBS) and motor cortex stimulation (MCS) in context to emerging indications in neuromodulation. Consideration for neuromodulatory treatment begins with rigorous patient selection based on exhaustive conservative management, elimination of secondary gains, and a proper psychology evaluation. Trial stimulation prior to DBS is nearly always performed while trial stimulation prior to MCS surgery is symptom dependent. Overall, a review of the literature demonstrates that DBS should be considered for refractory conditions including nociceptive/neuropathic pain, phantom limb pain, and chronic cluster headache (CCH). MCS should be considered primarily for trigeminal neuropathic pain (TNP) and central pain. DBS outcome studies for post-stroke pain as well as MCS studies for complex regional pain syndrome (CRPS) show more modest results and are also discussed in detail.


Assuntos
Estimulação Encefálica Profunda , Córtex Motor/fisiopatologia , Neuralgia/terapia , Dor Intratável/terapia , Ensaios Clínicos como Assunto , Estimulação Encefálica Profunda/métodos , Humanos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/fisiopatologia
14.
Breast ; 22(6): 1081-6, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23948301

RESUMO

BACKGROUND: Sentinel node biopsy (SNB) was initially conceived as excision of the first station axillary lymph node(s) (LN) identified by radioactive and/or blue dye uptake. The definition was subsequently enlarged to also include palpable lymph nodes in the vicinity of sentinel node(s) (SN). We reasoned that the excision of this combination of nodes might be best achieved by sampling the lower axilla. METHODS: Each patient underwent low axillary sampling (LAS) and identification of SN in the excised specimen followed by complete axillary lymph node dissection (ALND). LAS was defined as excision of all fibrofatty tissue overlying the second digitation of serratus anterior below the intercostobrachial nerve and was carried out following a pre-operative injection of radioactive colloid and an intra-operative injection of blue dye. Blue and/or hot nodes (B&/HN) in the dissected tissue and remaining axilla, along with any palpable nodes within the sampled tissue, were defined as SN. The primary endpoint of the study was to compare false negative rates (FNR) of SN with that of LAS in predicting axillary LN status (NCT00128362). FINDINGS: The study was performed between March 2004 and December 2011 in 478 women with clinically node negative axilla. On histopathological evaluation the median tumor size was 2.5 cm and axillary nodal metastases were found in 34.1% of patients. The FNR of SNB (12.7%, 95% CI 8.1-19.4) and LAS (10.5%, 95% CI 6.6-16.2) were not significantly different (p = 0.56). The FNR of B&/HN alone, without palpable nodes, (29.0%, 95% CI 22.5-36.6) was significantly inferior to those of SNB (p = 0.0007) and LAS (p = 0.0003). INTERPRETATION: LAS is as accurate as SNB in predicting axillary LN status in women with clinically node negative operable breast cancer. Confining SNB procedure to excision of B&/HN, significantly increases the risk of leaving behind metastatic lymph nodes in the axilla. LAS is an effective and low cost procedure that minimizes axillary surgery and can be implemented widely. Registry Name: Clinicaltrials.gov. REGISTRATION NUMBER: NCT00128362.


Assuntos
Neoplasias da Mama/patologia , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Biópsia de Linfonodo Sentinela , Tecido Adiposo/cirurgia , Axila , Neoplasias da Mama/cirurgia , Corantes , Reações Falso-Negativas , Feminino , Humanos , Linfonodos/diagnóstico por imagem , Metástase Linfática , Azul de Metileno , Pessoa de Meia-Idade , Cintilografia , Compostos Radiofarmacêuticos , Coloide de Enxofre Marcado com Tecnécio Tc 99m
15.
Cell Death Dis ; 3: e402, 2012 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-23059821

RESUMO

DAMTC (7,8-diacetoxy-4-methylcoumarin) is a thioderivative of 4-methyl coumarin, and previously we have shown that DAMTC is a potent inhibitor of cell growth and an inducer of apoptosis in non-small cell lung cancer (A549) cells. It induces apoptosis through mitochondrial pathway by modulating NF-κB, mitogen-activated protein kinase (MAPK) and p53 pathways. Herein, we explored the genome-wide effects of DAMTC in A549 cells using the concerted approach of transcriptomics and proteomics. In addition to apoptotic pathways, which have been validated earlier, the bioinformatic analysis of microarray data identified small GTPase-mediated signal transduction among the significantly altered biological processes. Interestingly, we observed significant downregulation of some members of the Rho family GTPases in the proteomics data too. Downregulation of Rho GTPases (RhoGDIα (Rho GDP dissociation inhibitor-α, also known as ARHGDIA), Ras homolog family member A, Ras-related C3 botulinum toxin substrate 1 and cell division cycle 42) was validated by western blotting. The Rho protein family is implicated in maintaining the actin filament assembly and cell motility, and we also observed that DAMTC treatment causes actin cytoskeletal reorganization, promotes filopodia formation and inhibits cell motility in A549 cells. The effect of DAMTC treatment on cytoskeleton was reversed after the overexpression of RhoGDIα. In addition, DAMTC augmented the apoptotic effect of etoposide, a proapoptotic chemotherapeutic drug. This elucidation of the mechanism behind DAMTC-induced apoptosis and inhibition of cell motility in A549 cells may make it a potential therapeutic for lung cancer.


Assuntos
Movimento Celular/efeitos dos fármacos , Cumarínicos/farmacologia , Citoesqueleto/efeitos dos fármacos , Proteômica , Transcriptoma/efeitos dos fármacos , Actinas/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Cumarínicos/química , Citoesqueleto/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo , Proteína Desglicase DJ-1 , Transdução de Sinais , Proteínas rho de Ligação ao GTP/metabolismo , Inibidor alfa de Dissociação do Nucleotídeo Guanina rho/genética , Inibidor alfa de Dissociação do Nucleotídeo Guanina rho/metabolismo
16.
J Pharm Bioallied Sci ; 4(Suppl 1): S74-6, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23066214

RESUMO

Spray formulation can minimize pain and irritation experience during the application of conventional dosage forms. Econazole Nitrate is an active ingredient of the aerosol concentrate to be used for twice-daily application because of its long durability in the superficial layers of the fungal infected skin. The aim of this study is preliminary investigation of Econazole Nitrate spray by varying the concentrations of different constituents of the spray. The ratios of Propylene glycol (PG) and isopropyl myristate (IPM) were selected as independent variables in 2(2) full factorial designs, keeping the concentration of solvent, co-solvent and propellant LPG constant. Aerosol also contained Ethanol as solvent and Isopropyl alcohol as co-solvent. All ingredients of the aerosol were packaged in an aluminum container fitted with continuous-spray valves. Physical properties evaluated for the Econazole Nitrate spray included delivery rate, delivery amount, pressure, minimum fill, leakage, flammability, spray patterns, particle image and plume angle. Glass containers were used to study incompatibility between concentrate and propellant due to the ease of visible inspection. Isopropyl myristate at lower concentrate showed turbidity, while at high concentration it met the requirements for aerosol and produced Econazole Nitrate spray with expected characteristics.

17.
Natl Med J India ; 25(3): 132-6, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22963288

RESUMO

BACKGROUND: Neoadjuvant chemotherapy is now the standard approach for most large breast cancers including locally advanced cancers of the breast. The majority of patients respond satisfactorily to chemotherapy with effective downsizing of tumours to consider breast conservation surgery. Pathological complete response (pathCR) is known to be a strong predictor of good outcome; however, many factors are known to influence the extent of response to chemotherapy. It has been observed that smaller the tumour, better is the response achieved in contrast to larger and locally advanced tumours where only one-third may respond well enough to merit breast conservation. Various other clinical, biological and molecular factors are also being evaluated as effective predictors of chemosensitivity. Most of these are either not easily available for all patients in developing countries or are overtly expensive and not applicable for all patients. METHODS: We evaluated the clinical and pathological predictors of response to chemotherapy in 1402 women with locally advanced breast cancer. RESULTS: There was a higher rate of pathCR in smaller tumours, younger women and ER-negative as well as triple negative tumours. The presence of ductal carcinoma in situ (DCIS) and lymphatic and vascular invasion (LVI) were associated with lower pathCR. CONCLUSION: In the absence of ready availability of expensive molecular and genomic assays, clinical parameters and standard histopathological variables can also be useful indicators of response to neoadjuvant chemotherapy. Additionally, they can help identify those who could be eventually conserved or have a better outcome.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carcinoma Ductal/tratamento farmacológico , Carcinoma Ductal/patologia , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Carcinoma in Situ/tratamento farmacológico , Carcinoma in Situ/metabolismo , Carcinoma in Situ/patologia , Carcinoma Ductal/metabolismo , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Pessoa de Meia-Idade , Valor Preditivo dos Testes
18.
Work ; 41 Suppl 1: 3404-11, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22317239

RESUMO

Subjective Visual Disturbances are silent adversaries that appear over a period of continued exposure and arise when the visual demands of the tasks exceed the visual abilities of the user. Jewellery manufacturing activity involves precision designs, setting the metal and stones, polishing and filing which requires higher visual demand. Therefore, it is expected that the jewellery manufacturing workers may experience subjective visual disturbances. This study was taken up with the following objectives 1) To study the presence of subjective visual disturbances among jewellery manufacturing workers and compare the same with VDT operators 2) To study the effect of work exposures on subjective visual disturbances and 3) to ascertain whether subjective visual disturbances have any permanent vision related problems. The study was carried out on jewellery manufacturing workers, VDT operators and on graduate students. The symptoms of subjective visual disturbances were identified using a questionnaire developed by Sheedy (2003). Viewing distances were measured and visual angles were calculated. The eye check--ups were also carried out. The subjective visual disturbances were higher in jewellery manufacturing workers. The findings suggest that work exposure has an impact on the causation of subjective visual disturbances. No pathological conditions of the eyes were observed.


Assuntos
Oftalmopatias/epidemiologia , Joias , Doenças Profissionais/epidemiologia , Adolescente , Adulto , Terminais de Computador , Técnicas de Diagnóstico Oftalmológico , Oftalmopatias/diagnóstico , Humanos , Índia/epidemiologia , Masculino , Doenças Profissionais/diagnóstico , Prevalência , Adulto Jovem
19.
Clin Oncol (R Coll Radiol) ; 24(9): 604-9, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22014455

RESUMO

AIM: To study the toxicity profile and response rates of weekly paclitaxel given as neoadjuvant chemotherapy (NACT) in patients with locally advanced breast cancer. MATERIALS AND METHODS: The study was planned as a single arm, prospective phase II study. Twenty-six patients with locally advanced breast cancer were enrolled in the study from December 2006 to October 2007. These patients underwent NACT with weekly paclitaxel at 100 mg/m(2) for 8 consecutive weeks followed by surgery. This was followed by anthracycline-based chemotherapy for three to four cycles followed by radiation. The patients received standard adjuvant hormonal therapy. The patients were carefully monitored for side-effects using common toxicity criteria. The clinical and pathological response rates were documented. The response rates were descriptively stated. RESULTS: The median age of the patients was 52 years (30-67 years) and the median tumour size was 7 cm (2.5-15 cm). Of the 208 planned weekly cycles, 207 could be given. The rates of grade 3-4 neutropenia, thrombocytopenia and neuropathy were 4, 12 and 4%, respectively. A complete clinical response was observed in 10 patients (38.5%) and a completed pathological response, defined as the absence of invasive cancer from the breast and axillary nodes, was seen in 11.5% of patients. Breast-conserving surgery was possible in 23% of patients. CONCLUSION: The regimen of weekly single agent paclitaxel is feasible in patients with locally advanced breast cancer with acceptable toxicity. It resulted in a pathological response rate that was comparable with other regimens in this group of advanced stage patients. Considering the efficacy and low toxicity of this regimen, it is worth exploring in larger studies.


Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico , Adulto , Idoso , Neoplasias da Mama/patologia , Esquema de Medicação , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Estudos Prospectivos
20.
Curr Med Chem ; 18(25): 3758-824, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21831039

RESUMO

Prunus is a genus of trees and shrubs, including the plums, cherries, peaches, apricots and almonds. Nearly five hundred seventy chemical compounds have so far been isolated from several Prunus species. This comprehensive review summarizes the isolation of chemical compounds reported during the period 1908 to June 2010. As per scrutiny of literature, we did not find any review on the chemistry or biology of genus Prunus or on the biological activities of its constituents. Extensive work has been done at the Department of Chemistry, University of Delhi by several groups on the isolation, identification, biological activity evaluation and synthesis of a large number of novel compounds from different Prunus species during the the last six decades (1940-2000), primarly by Seshadri, Nagarajan and Parmar et al. on P. domestica, P. cerasus, P. cerasoides, P. puddum and P. communis. This comprehensive review will benefit a large number of researchers in the fields of chemistry, botany, drug industries and pharmacology.


Assuntos
Extratos Vegetais/química , Extratos Vegetais/farmacologia , Prunus/química , Animais , Carotenoides/química , Carotenoides/isolamento & purificação , Carotenoides/farmacologia , Cumarínicos/química , Cumarínicos/isolamento & purificação , Cumarínicos/farmacologia , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Humanos , Extratos Vegetais/isolamento & purificação , Esteroides/química , Esteroides/isolamento & purificação , Esteroides/farmacologia
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