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1.
J Indian Assoc Pediatr Surg ; 28(4): 325-327, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37635883

RESUMO

A 4-year-old male child presented with complaints of abdominal pain and vomiting along with yellowish discoloration of the eyes. Investigations were suggestive of acute pancreatitis and double gall bladder (GB) with dilated common bile duct (CBD) with intraluminal calculi and Type II choledochal cyst. He underwent surgical resection of double GB with dilated CBD with hepatico-docho-jejunostomy. On follow-up, the patient was asymptomatic. Our case highlights the importance of preoperative diagnosis to deal with increased operative difficulty and complications.

2.
J Indian Assoc Pediatr Surg ; 26(1): 44-47, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33953512

RESUMO

Pancreatic pseudocysts are cystic cavities which are localized collection of pancreatic secretions, rich in amylase and other enzymes, present in and around pancreas, encased in a false epithelial lining of fibrous or reactive granulation tissue. Extension of a pancreatic pseudocyst into the mediastinum is rare. We are reporting a case of a 5-year-old child with mediastinal pancreatic pseudocyst which was successfully drained by cystojejunostomy.

3.
J Indian Assoc Pediatr Surg ; 26(2): 120-122, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34083897

RESUMO

Foreign body ingestion is common in young children. Very few cases require surgical exploration for removal. We report a case of superabsorbent gel ball ingestion causing intestinal obstruction, managed by a combination of endoscopic and open surgical removal under intraoperative ultrasound guidance.

4.
J Indian Assoc Pediatr Surg ; 26(3): 144-147, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34321784

RESUMO

AIM: The aim of this study is to compare suction rectal biopsy (SRB) with full-thickness rectal biopsy (FTRB) in suspected cases of Hirschsprung's disease (HD). MATERIALS AND METHODS: Between 2014 and 2018, we enrolled 41 consecutive children with suspected HD. We analyzed demographics, sex, age, clinical symptoms, radiological images, and biopsy reports. All the children had undergone X-ray of the abdomen and pelvis and contrast enema. All of them have undergone both SRB and FTRB, and their results were compared. RESULTS: Out of 41 children, 26 were male and 15 were female. The children were aged from 5 days to 12 years. All of them presented with delayed passage of meconium, abdominal distension, and severe constipation. They all were on oral laxatives. The sensitivity and specificity of SRB are 80.95% and 90.00% when compared to FTRB which has 100% and 100%, respectively. CONCLUSION: FTRB is the gold standard test for diagnosing HD. SRB may be a good screening test in suspected HD cases. SRB is not as equal and effective as FTRB for diagnosing HD.

5.
J Indian Assoc Pediatr Surg ; 25(6): 390-392, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33487943

RESUMO

Anorectal malformations (ARMs) have coexisting congenital anomalies. These can affect the overall prognosis. Anomalous craniofacial associations are less common. Recently, we managed two patients of ARM associated with unilateral microphthalmia, without any other major systemic anomalies. This was found to be a rare association on extensive literature search.

6.
J Indian Assoc Pediatr Surg ; 25(5): 280-285, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33343108

RESUMO

AIM: To find out association between liver function, liver histopathology and outcomes of biliary atresia (BA) following Kasai Portoenterostomy (KPE). MATERIALS AND METHODS: This is a retrospective study of children who underwent KPE at a single institute by single surgeon. The patient records analyzed and data of complete blood counts, liver function tests, coagulation profile and histopathology reports collected. The outcomes recorded as alive and jaundice free, alive but jaundiced, and deceased. Statistical analysis done using SPSS 23. OBSERVATIONS: Total of 148 children operated during January 2000 to December 2018. Of these, 26 matched inclusion criteria. The parameters assessed were percentage of direct bilirubin, ratios of Aspartate transaminase (AST) to Alanine transaminase (ALT); Gamma glutamyl transferase (GGT) to AST; GGT to ALT and Aspartate transaminase to platelet ratio index (APRi). Among histopathology reports, fibrosis grade and bile ductular size noted. Among 26, 16 alive and ten are deceased. Among 16 alive, all are jaundice free. Of the parameters, ratio of AST to ALT, APRi and grade of fibrosis found statistically significant and further analysis showed if AST to ALT ratio < 2.1, APRi < 1.8 and grade of fibrosis < four, irrespective of age at surgery, had 96.2 % probability of successful KPE. Based on these observations, a scoring system and risk prediction model constructed based on Receiver operating characteristic (ROC) curves which are first in BA management. RESULTS AND CONCLUSION: Although numbers are sufficient for statistical analysis, we further intend to validate the scoring system in a prospective trial. BA children can be subjected to risk prediction model and KPE performed in those who have a score less than seven and offered to those with score between eight and 16 out of 20. KEY MESSAGE: The scoring system and risk prediction model can guide in the management and post-operative follow up of children with biliary atresia.

7.
Proc Natl Acad Sci U S A ; 113(44): 12408-12413, 2016 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-27791090

RESUMO

People who are more avoidant of pathogens are more politically conservative, as are nations with greater parasite stress. In the current research, we test two prominent hypotheses that have been proposed as explanations for these relationships. The first, which is an intragroup account, holds that these relationships between pathogens and politics are based on motivations to adhere to local norms, which are sometimes shaped by cultural evolution to have pathogen-neutralizing properties. The second, which is an intergroup account, holds that these same relationships are based on motivations to avoid contact with outgroups, who might pose greater infectious disease threats than ingroup members. Results from a study surveying 11,501 participants across 30 nations are more consistent with the intragroup account than with the intergroup account. National parasite stress relates to traditionalism (an aspect of conservatism especially related to adherence to group norms) but not to social dominance orientation (SDO; an aspect of conservatism especially related to endorsements of intergroup barriers and negativity toward ethnic and racial outgroups). Further, individual differences in pathogen-avoidance motives (i.e., disgust sensitivity) relate more strongly to traditionalism than to SDO within the 30 nations.


Assuntos
Doenças Transmissíveis/parasitologia , Individualidade , Modelos Psicológicos , Parasitos/fisiologia , Política , Adulto , Animais , Atitude , Doenças Transmissíveis/psicologia , Feminino , Humanos , Masculino , Predomínio Social , Inquéritos e Questionários , Adulto Jovem
8.
Cogn Emot ; 30(1): 20-32, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-25787295

RESUMO

We investigated the intensely positive emotional experiences arising from participation in a large-scale collective event. We predicted such experiences arise when those attending a collective event are (1) able to enact their valued collective identity and (2) experience close relations with other participants. In turn, we predicted both of these to be more likely when participants perceived crowd members to share a common collective identity. We investigated these predictions in a survey of pilgrims (N = 416) attending a month-long Hindu pilgrimage festival in north India. We found participants' perceptions of a shared identity amongst crowd members had an indirect effect on their positive experience at the event through (1) increasing participants' sense that they were able to enact their collective identity and (2) increasing the sense of intimacy with other crowd members. We discuss the implications of these data for how crowd emotion should be conceptualised.


Assuntos
Emoções , Processos Grupais , Identificação Social , Percepção Social , Idoso , Feminino , Humanos , Relações Interpessoais , Masculino , Comportamento de Massa , Comportamento Social
9.
Exp Cell Res ; 317(10): 1368-81, 2011 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-21473864

RESUMO

Unlike the well-characterized nuclear function of the Notch intracellular domain, it has been difficult to identify a nuclear role for the ligands of Notch. Here we provide evidence for the nuclear function of the Notch ligand Delta-like 1 in colon cancer (CC) cells exposed to butyrate. We demonstrate that the intracellular domain of Delta-like 1 (Dll1icd) augments the activity of Wnt signaling-dependent reporters and that of the promoter of the connective tissue growth factor (CTGF) gene. Data suggest that Dll1icd upregulates CTGF promoter activity through both direct and indirect mechanisms. The direct mechanism is supported by co-immunoprecipitation of endogenous Smad2/3 proteins and Dll1 and by chromatin immunoprecipitation analyses that revealed the occupancy of Dll1icd on CTGF promoter sequences containing a Smad binding element. The indirect upregulation of CTGF expression by Dll1 is likely due to the ability of Dll1icd to increase Wnt signaling, a pathway that targets CTGF. CTGF expression is induced in butyrate-treated CC cells and results from clonal growth assays support a role for CTGF in the cell growth-suppressive role of butyrate. In conclusion, integration of the Notch, Wnt, and TGFbeta/Activin signaling pathways is in part mediated by the interactions of Dll1 with Smad2/3 and Tcf4.


Assuntos
Ativinas/metabolismo , Núcleo Celular/metabolismo , Neoplasias do Colo/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas de Membrana/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Proteínas Wnt/metabolismo , Apoptose/efeitos dos fármacos , Western Blotting , Butiratos/farmacologia , Proteínas de Ligação ao Cálcio , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Imunoprecipitação da Cromatina , Neoplasias do Colo/tratamento farmacológico , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Humanos , Imunoprecipitação , Luciferases/metabolismo , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Células Tumorais Cultivadas
10.
BMJ Case Rep ; 15(3)2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35304355

RESUMO

Superior mesenteric artery syndrome (SMAS), also known as Wilkie's syndrome, is a rare cause of upper gastrointestinal tract obstruction. We report a case of a 10-year-old girl with persistent abdominal pain for over 3 months, who on extensive investigations was diagnosed with SMAS. She underwent a surgical procedure to bypass the obstructed portion of the intestine for relief of her symptoms.


Assuntos
Síndrome da Artéria Mesentérica Superior , Criança , Família , Feminino , Humanos , Síndrome da Artéria Mesentérica Superior/diagnóstico , Síndrome da Artéria Mesentérica Superior/diagnóstico por imagem
11.
Br J Soc Psychol ; 60(2): 678-699, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32856331

RESUMO

Much research addresses the proposition that identifying with a group shapes individuals' behaviour. Typically, such research employs experimental or survey methods, measuring or manipulating social identification and relating this to various outcome variables. Although shedding much light on the processes involved in the identity-behaviour relationship, such research tends to overlook the various constraints that limit individuals' abilities to act in accordance with their identities. Using interview data gathered in north India, we explore the factors affecting the enactment of a religious identity. More specifically, using data gathered at a religious mass gathering, we compare and contrast participants' reports of identity enactment when they are at the event and when they are in their home villages. These two contexts differ in terms of their social organization, especially the degree to which they are marked by the presence of a shared identity. Exploring participants' accounts of such differences in social organization, we consider the social processes that constrain or facilitate identity enactment. In so doing, our analysis contributes to a richer analysis of the identity-behaviour relationship.


Assuntos
Férias e Feriados , Identificação Social , Humanos , Inquéritos e Questionários
12.
Biochem Biophys Res Commun ; 391(1): 674-8, 2010 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-19961831

RESUMO

Obesity is associated with low-grade inflammation in adipose tissue, which contributes to the development of obesity-related diseases such as insulin resistance, hypertension and arteriosclerosis. Here we developed an animal model that non-invasively monitors inflammation in adipose tissue using in vivo bioluminescent imaging (BLI) technique. In vitro, stimulation with TNFalpha or co-culture with RAW264 macrophages increased bioluminescence in 3T3-L1 adipocytes expressing NF-kappaB-mediated luciferase gene (3T3-L1/NF-kappaB-re-luc2P). In vivo, lipopolysaccharide increased bioluminescence in mice transplanted with 3T3-L1/NF-kappaB-re-luc2P cells. Moreover, light emission derived from implanted cells was significantly higher in diet-induced obese mice transplanted with 3T3-L1/NF-kappaB-re-luc2P than in lean mice. Our results showed that BLI technique and 3T3-L1/NF-kappaB-re-luc2P cells provide a useful approach to non-invasively monitor obesity-induced inflammation in adipose tissue in in vivo.


Assuntos
Tecido Adiposo/patologia , Inflamação/patologia , Medições Luminescentes , Obesidade/patologia , Células 3T3-L1 , Animais , Modelos Animais de Doenças , Genes Reporter , Inflamação/etiologia , Lipopolissacarídeos , Luciferases/genética , Masculino , Camundongos , Camundongos SCID , Monitorização Fisiológica , NF-kappa B/metabolismo
13.
R Soc Open Sci ; 7(11): 201063, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33391796

RESUMO

Given top-down effects on perception, we examined the effect of group identity on time perception. We investigated whether the duration of an ambiguous sound clip is processed differently as a function of group congruent or incongruent source attribution. Group congruent (in-group) and incongruent (out-group) context was created by attributing the source of an identical ambiguous sound clip to Hindu or Muslim festivals. Participants from both the religious groups (Hindus and Muslims) prospectively listened to a 20 s long ambiguous sound clip and reproduced its duration (experiment 1a). Both groups reproduced significantly longer durations when the sound clip was associated with the group congruent compared to the group incongruent festival contexts. The two groups did not differ significantly in reproduced duration when the sound attributed to a non-religious common (busy city street) context (experiment 1b). With multiple durations (1, 5, 10 and 20 s), longer durations were reproduced for group congruent labelling at objectively longer durations (experiment 2). According to the internal clock model of time perception, the significant slope effect indicated that the group congruent context influences temporal experience through changes in pacemaker frequency. We argue that the duration appearing relevant to one's own group is processed differently possibly owing to differences in attentional deployment, which influences the pacemaker frequency.

14.
J Pediatr Surg ; 55(10): 2183-2186, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32553452

RESUMO

INTRODUCTION: Budd-Chiari syndrome (BCS) is a rare condition affecting children. It is characterized by occlusion of venous outflow from liver at the level of hepatic veins (HV) or inferior vena cava (IVC). The management of BCS in children revolves around forming new collaterals for venous outflow or by elimination of blockage in the venous outflow tracts. These can be achieved by balloon venoplasty (BV), transjugular intrahepatic portosystemic shunting (TIPSS) or open shunt surgeries. AIM: The aim of this study is to evaluate the management of BCS in children with balloon venoplasty as primary modality of treatment. MATERIALS AND METHODS: This is a retrospective study which includes children diagnosed with BCS managed by balloon venoplasty by a single surgeon at a single institute. Once confirmed, the child was posted for balloon venoplasty and liver biopsy. When venoplasty was successful, child was subsequently heparinized and dose titrated. Routine follow up was mandated and dose adjustments were continued during follow up. In case of unsuccessful venoplasty, depending on the liver biopsy report, shunt procedure or liver transplantation is offered to patients. An algorithm was then designed for management of BCS in children. RESULTS: A total of 35 children who underwent evaluation of symptoms associated with Budd-Chiari syndrome were included in the study. Of all the children, 14 are alive and symptom free, 9 are deceased and 12 lost to follow up. Hepatic vein was the most common site of obstruction (85%), followed by both IVC and HV (15%). Overall, in 35 children, 26 had a successful balloon venoplasty, in 3 venoplasty was not done (2 spontaneous resolution and 1 died awaiting), in 6 it was unsuccessful (3 technical failures: 1 underwent TIPSS and 2 lost to follow up, 3 clinical failures: portocaval shunt for failed venoplasty). CONCLUSION: Budd-Chiari syndrome is a rare condition affecting children. Balloon venoplasty as a primary modality of treatment for BCS is a promising option for management in children. Early and aggressive use of radiological intervention can help achieve recanalization in children. TYPE OF STUDY: Clinical research paper. LEVEL OF EVIDENCE: Level IV.


Assuntos
Angioplastia com Balão , Síndrome de Budd-Chiari/cirurgia , Veias Hepáticas/cirurgia , Veia Cava Inferior/cirurgia , Algoritmos , Biópsia , Síndrome de Budd-Chiari/complicações , Síndrome de Budd-Chiari/diagnóstico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Fígado/patologia , Transplante de Fígado , Masculino , Derivação Portossistêmica Transjugular Intra-Hepática , Estudos Retrospectivos , Resultado do Tratamento
15.
Philos Trans R Soc Lond B Biol Sci ; 375(1805): 20190430, 2020 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-32594880

RESUMO

Rituals are performed within specific socio-ecological niches, yet the different effects of the same ritual form across different niches (community contexts) remains unclear. Here, using longitudinal measures over a two-week period during Diwali (the Indian festival of light), we investigate the relationship between ritual time allocation and social cohesion in two Indian communities. First, the positive effects of ritual on social bonding, perceived health and affect were highest on the focal day of the festival. Second, we observed anticipatory effects of ritualistic commitment on affect prior to the main day of the festival. Third, social bonding patterns were similar in the two Indian settings, indicating that Diwali fosters social cohesion across diverse social ecologies (cultural niches). However, individually focused emotional benefits appear to dampened in more cosmopolitan environments. Finally, time investments reveal diminishing marginal utilities for ritual activities on social cognition. Ritual time investments were linked to greater affect and family cohesion up to a certain limit. We argue that attention to the diminishing returns of ritual time investments on social cohesion across diverse human ecologies is an important horizon for future cross-cultural investigations. This article is part of the theme issue 'Ritual renaissance: new insights into the most human of behaviours'.


Assuntos
Afeto , Comportamento Ritualístico , Autoavaliação Diagnóstica , Comportamento Social , Humanos , Índia , Estudos Longitudinais
16.
Afr J Paediatr Surg ; 15(1): 31-35, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30829306

RESUMO

BACKGROUND: Chronic refractory constipation (CRC) is an uncommon type of constipation. These children have persistent symptoms even after treatment with high dose laxatives, which may cause abdominal distension, vomiting, cramping and bloating. We conducted this study to assess the diagnostic and therapeutic role of anorectal myomectomy in children with CRC. MATERIALS AND METHODS: This study includes 107 patients who fit the criteria of CRC. Complete bowel preparation with polyethylene glycol solution, enemas and antibiotics was carried out before surgery in all patients. The anorectal myomectomy was carried out under general anaesthesia with the patient in the high lithotomy position. The patients were followed up from 6 months to 13 years postoperatively. The success of myomectomy was based on the daily and complete passage of stools without the need for medication or enemas. RESULTS: A total of 99 patients were included in the study, of which, 86 (86.86%) patients showed a good response to anorectal myomectomy. Of these, 32 patients had normal histology, 14 had histology suggestive of Hirschsprung's disease, 8 had hypoganglionosis, 10 had ultra-short segment Hirschsprung's disease and 22 had hypertrophic nerves with immature ganglia. Poor response was seen in 13 (13.13%) patients of whom 5 had normal histology, 5 had Hirschsprung's disease, 2 had hypoganglionosis and 1 had ultra-short segment Hirschsprung's disease. CONCLUSION: Anorectal myomectomy is an effective and technically simple procedure in selected patients with CRC for both diagnostic and therapeutic purposes.


Assuntos
Canal Anal/cirurgia , Constipação Intestinal/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Previsões , Doença de Hirschsprung/cirurgia , Reto/cirurgia , Criança , Pré-Escolar , Doença Crônica , Constipação Intestinal/etiologia , Constipação Intestinal/fisiopatologia , Defecação/fisiologia , Feminino , Seguimentos , Doença de Hirschsprung/complicações , Humanos , Lactente , Masculino , Resultado do Tratamento
17.
Int J Surg Case Rep ; 41: 407-410, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29546003

RESUMO

This case report has been reported in line with the SCARE criteria; Consensus-based surgical case report guidelines of International Journal of Surgery 2016. INTRODUCTION: Transverse Testicular Ectopia (TTE) is a rare condition which manifests with unilateral undescended testis and contralateral hernia. Till now around 100 cases have been described in the literature. The management depends on the anatomy of the vas, vessels and testis found on surgical exploration. An algorithm exists for its management and we propose a modified algorithm for management of TTE. CASE PRESENTATION: Five year male presented with complaints of unilateral undescended testis on the right and hernia on the left. Clinically the right testis was impalpable and left testis palpable in the left hemiscrotum and fluid hernia on the same side. DISCUSSION: Transverse testicular ectopia is a rare condition presenting with UDT and contralateral inguinal hernia. Although more than 100 cases have been described in the literature so far, those managed with a transeptal contralateral orchidopexy are two cases to the best of our knowledge. TTE was first described by Von Lenhossek in 1886. The mean age of presentation is around 4 years and most of the cases are diagnosed on surgical exploration. The management of TTE remains controversial even though an algorithm has been described for its management due to its varied presenting scenarios. CONCLUSION: TTE is a rare condition which requires high index of suspicion for diagnosis preoperatively. Whenever suspected we recommend an USG and/or MRI prior to diagnostic laparoscopy and proceed with orchidopexy. Diagnostic laparoscopy is both helpful in diagnosis and management. Transeptal contralateral orchidopexy gives good tension free fixation of testes in the scrotum.

18.
Eur J Soc Psychol ; 44(7): 787-798, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26160989

RESUMO

Identifying with a group can contribute to a sense of well-being. The mechanisms involved are diverse: social identification with a group can impact individuals' beliefs about issues such as their connections with others, the availability of social support, the meaningfulness of existence, and the continuity of their identity. Yet, there seems to be a common theme to these mechanisms: identification with a group encourages the belief that one can cope with the stressors one faces (which is associated with better well-being). Our research investigated the relationship between identification, beliefs about coping, and well-being in a survey (N = 792) administered in rural North India. Using structural equation modelling, we found that social identification as a Hindu had positive and indirect associations with three measures of well-being through the belief that one can cope with everyday stressors. We also found residual associations between participants' social identification as a Hindu and two measures of well-being in which higher identification was associated with poorer well-being. We discuss these findings and their implication for understanding the relationship between social identification (especially with large-scale group memberships) and well-being. We also discuss the application of social psychological theory developed in the urban West to rural north India. © 2014 The Authors. European Journal of Social Psychology published by John Wiley & Sons, Ltd.

19.
PLoS One ; 7(10): e47291, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23082155

RESUMO

How does participation in a long-duration mass gathering (such as a pilgrimage event) impact well-being? There are good reasons to believe such collective events pose risks to health. There are risks associated with communicable diseases. Moreover, the physical conditions at such events (noise, crowding, harsh conditions) are often detrimental to well-being. Yet, at the same time, social psychological research suggests participation in group-related activities can impact well-being positively, and we therefore investigated if participating in a long-duration mass gathering can actually bring such benefits. In our research we studied one of the world's largest collective events - a demanding month-long Hindu religious festival in North India. Participants (comprising 416 pilgrims who attended the gathering for the whole month of its duration, and 127 controls who did not) completed measures of self-assessed well-being and symptoms of ill-health at two time points. The first was a month before the gathering commenced, the second was a month after it finished. We found that those participating in this collective event reported a longitudinal increase in well-being relative to those who did not participate. Our data therefore imply we should reconceptualise how mass gatherings impact individuals. Although such gatherings can entail significant health risks, the benefits for well-being also need recognition. Indeed, an exclusive focus on risk is misleading and limits our understanding of why such events may be so attractive. More importantly, as our research is longitudinal and includes a control group, our work adds robust evidence to the social psychological literature concerning the relationship between participation in social group activities and well-being.


Assuntos
Aglomeração/psicologia , Saúde , Hinduísmo , Participação Social , Feminino , Humanos , Índia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
20.
PLoS One ; 6(11): e27308, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22073312

RESUMO

Butyrate, a fermentation product of fiber in the colon, acts as a histone deacetylase inhibitor (HDACi) and induces apoptosis in colon cancer (CC) cells in vitro. We have reported that the apoptotic effects of butyrate are dependent upon the hyperactivation of the Wnt/beta-catenin pathway. However, prolonged exposure of CC cells to increasing concentrations of butyrate results in the acquisition of resistance to the Wnt/beta-catenin- and apoptosis-inducing effects of this agent, as well as cross-resistance to structurally different HDACis. Here we report that one mechanism whereby HDACi resistance arises is through the increase of beta-catenin-independent (noncanonical) Wnt signaling. Compared to HDACi-sensitive HCT-116 CC cells, HDACi-resistant HCT-R cells exhibit higher levels of AKT/PKB cell survival signaling, which is in part induced by WNT5A and its receptor ROR2. The induction of AKT signaling by HDACis is also detected in other CC cell lines, albeit to a lesser extent than in the drug-resistant HCT-R cells. The observations suggested that the apoptotic effect of butyrate and other HDACis in CC cells can be augmented by inhibitors of pAKT. In agreement with the hypothesis, the combination of MK2206, a pAKT inhibitor, and a HDACi (butyrate or LBH589) induced higher apoptosis in CC cells compared to each agent alone. The exposure to both agents also re-sensitized the HCT-R cells to apoptosis. Finally, the concept of simultaneously inducing canonical Wnt activity and suppressing AKT signaling was translated into a combination of diet-derived agents. Diet-derived pAKT inhibitors (caffeic acid phethyl ester, sulforaphane, dilallyl trisulfide) suppressed the butyrate-induced levels of pAKT, and increased the apoptotic effects of butyrate in both drug-sensitive and drug-resistant CC cells.Our findings can be translated into (a) CC therapy employing combinations of synthetic HDACis and inhibitors of pAKT, as well as (b) CC prevention based upon diets that result in sufficient amounts of butyrate and pAKT inhibitors.


Assuntos
Neoplasias do Colo/metabolismo , Resistencia a Medicamentos Antineoplásicos , Transdução de Sinais , Proteínas Wnt/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias do Colo/patologia , Inibidores de Histona Desacetilases/farmacologia , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo
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