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2.
J Minim Access Surg ; 19(3): 450-452, 2023.
Article in English | MEDLINE | ID: mdl-37282442

ABSTRACT

Standard minimally invasive Ivor Lewis oesophagectomy is performed through a multiport technique using carbon dioxide. However, access to video-assisted thoracoscopic surgery (VATS) is increasingly shifting to a single-port approach due to its proven safety and efficacy in lung surgeries. Therefore, the preamble of this submission is to describe, 'How I do differently' uniportal VATS MIO in three major steps: (a) VATS dissection through a single 4-cm incision in a semi-prone position without artificial capnothorax; (b) fluorescence dye to check conduit perfusion and (c) intrathoracic overlay anastomosis with a linear stapler.

3.
Am J Med Genet A ; 188(3): 788-805, 2022 03.
Article in English | MEDLINE | ID: mdl-34863015

ABSTRACT

Hypohidrotic ectodermal dysplasia (HED) is a rare genetic disorder caused by mutational inactivation of a developmental pathway responsible for generation of tissues of ectodermal origin. The X-linked form accounts for the majority of HED cases and is caused by Ectodysplasin (EDA) pathogenic variants. We performed a combined analysis of 29 X-linked hypohidrotic ectodermal dysplasia (XLHED) families (including 12 from our previous studies). In addition to the classical triad of symptoms including loss (or reduction) of ectodermal structures, such as hair, teeth, and sweat glands, we detected additional HED-related clinical features including facial dysmorphism and hyperpigmentation in several patients. Interestingly, global developmental delay was identified as an unusual clinical symptom in many patients. More importantly, we identified 22 causal pathogenic variants that included 15 missense, four small in-dels, and one nonsense, splice site, and large deletion each. Interestingly, we detected 12 unique (India-specific) pathogenic variants. Of the 29 XLHED families analyzed, 11 (38%) harbored pathogenic variant localized to the furin cleavage site. A comparison with HGMD revealed significant differences in the frequency of missense pathogenic variants; involvement of specific exons and/or protein domains and transition/transversion ratios. A significantly higher proportion of missense pathogenic variants (33%) localized to the EDA furin cleavage when compared to HGMD (7%), of which p.R155C, p.R156C, and p.R156H were detected in three families each. Therefore, the first comprehensive analysis of XLHED from India has revealed several unique features including unusual clinical symptoms and high frequency of furin cleavage site pathogenic variants.


Subject(s)
Ectodermal Dysplasia 1, Anhidrotic , Ectodermal Dysplasia, Hypohidrotic, Autosomal Recessive , Ectodermal Dysplasia , Limb Deformities, Congenital , Ectodermal Dysplasia/genetics , Ectodermal Dysplasia 1, Anhidrotic/diagnosis , Ectodermal Dysplasia 1, Anhidrotic/genetics , Ectodysplasins/genetics , Furin/genetics , Humans , Pedigree
4.
Br J Cancer ; 121(11): 934-943, 2019 11.
Article in English | MEDLINE | ID: mdl-31673102

ABSTRACT

BACKGROUND: Interleukin-8 (IL-8) and heat shock protein 60 (Hsp60) play crucial roles in cell survival and maintenance of cellular homoeostasis. However, cross talks between these two proteins are not defined. METHODS: IL-8 expression in tumour tissue sections was analysed by immunohistochemistry. IL-8 expression and release in cancer cells was quantified using enzyme-linked immunosorbent assay (ELISA). Apoptosis was quantified using caspase activity and Annexin-V/PI staining. RESULTS: We observed IL-8 release from cancer cells in response to histone deacetylase inhibitor, apicidin (Api), and non-competitive inhibitor of the sarco/endoplasmic reticulum Ca2+ ATPase, thapsigargin (TG). IL-8 release was increased upon TG-treatment. TG-induced IL-8 expression was reduced in the presence of Api in Bax-dependent manner. Increased apoptosis was associated with decreased IL-8 expression in response to combined treatment of TG and Api. TG and Api combination induced caspase-8 and caspase-9 dependent apoptosis. Hsp60 knockdown abrogated IL-8 expression induced by Api, TG, and their combination. The level of TGF-ß, an upstream regulator of IL-8, was decreased upon Hsp60-silencing. Knocking down Hsp60 decreased IL-8 expression and its release in prostate cancer cell xenograft tumours in SCID mice. CONCLUSION: This study describes the underlying mechanism associated with apoptosis resistance mediated via Hsp60-IL-8 axis in cancer.


Subject(s)
Apoptosis/drug effects , Chaperonin 60/metabolism , Interleukin-8/metabolism , Mitochondrial Proteins/metabolism , Neoplasms/metabolism , Animals , Caspase 8/genetics , Caspase 9/genetics , Chaperonin 60/genetics , Gene Knockdown Techniques , HCT116 Cells , Heterografts , Humans , Interleukin-8/genetics , Male , Mice , Mice, SCID , Mitochondrial Proteins/genetics , Neoplasms/pathology , PC-3 Cells , Peptides, Cyclic/pharmacology , Signal Transduction/drug effects , Thapsigargin/pharmacology
5.
J Clin Diagn Res ; 11(1): UC09-UC12, 2017 Jan.
Article in English | MEDLINE | ID: mdl-28274023

ABSTRACT

INTRODUCTION: Awake intubation via Fiberoptic Bronchoscope (FB) is the gold standard for management of difficult airway but patients had to face problems like oxygen desaturation, tachycardia, hypertension and anxiety due to awake state. This study was conducted to assess feasibility of Fastrach Laryngeal Mask Airway (FLMA) to manage difficult airway as a conduit for intubation as well as for ventilation. MATERIALS AND METHODS: After ethical approval and informed consent, 60 patients with difficult airway were randomly enrolled in FB group and FLMA group. In FB group, patients were sedated with midazolam/fentanyl. Airway anaesthetization of oropharynx was done with xylocaine spray and viscous and larynx and trachea by superior laryngeal nerve block and transtracheal block respectively. In FLMA group, initially patients were induced with propofol for FLMA insertion then succinylcholine was given for Tracheal Intubation (TI). The first TI attempt was done blindly via the FLMA and all subsequent attempts were performed with fiberoptic guidance. Haemodynamic monitoring was done during induction, intubation, immediately post insertion and there after at five minutes interval for 30 minutes. RESULTS: All patients in the FLMA group were successfully ventilated (100%). In both the groups 28 (93.33%) patients were successfully intubated. However, first/second/third attempt intubation rate in FLMA vs FB group was 15 (50%) vs 13 (43.3%), 8 (26.66%) vs 10 (33.33%) and 5 (16.66%) in both groups respectively. Patients in the FLMA group were more satisfied with their method of TI and had lesser complications (p<0.05). CONCLUSION: So the FLMA may be a better technique for management of patients with difficult airways.

6.
J Clin Diagn Res ; 10(9): UC08-UC12, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27790554

ABSTRACT

INTRODUCTION: Postoperative pain after thoracotomy is being considered one of the most severe pain and if not treated well, can result in various respiratory and other complications. AIM: Present study was conducted with the aim to compare continuous thoracic epidural infusion with continuous paravertebral infusion for postoperative pain using Visual Analogue Scale (VAS) score and four point observer ranking. The secondary outcomes measured were pulmonary functions and any complication like hypotension, bradycardia, nausea, vomiting, urinary retention and neurological complications if any. MATERIALS AND METHODS: Sixty patients of age group 18-60 years posted for anterolateral thoracotomy surgery for lung resection were randomised either to epidural or paravertebral group in this randomised prospective double blind study. In Epidural group 7.5ml bolus of 0.125% Bupivacaine with 50µg Fentanyl and in Paravertebral group 15ml bolus of 0.125% Bupivacaine with 50µg Fentanyl was given 30 minutes before the anticipated end of surgery. Bolus dose was followed by infusion of 0.125% Bupivacaine with 2µg/ml Fentanyl at the rate of 5 ml/hr in both groups. Parameters noted were Mean Arterial Pressure (MAP), Heart Rate (HR), Oxygen Saturation (SpO2), Arterial Blood Gas (PaCO2, P/F ratio), Visual Analogue Scale (VAS) and Four Point Observer Ranking Scale (FPORS) for pain, number of sensory segments blocked (by checking for pinprick sensation), requirement of infusion top ups and rescue analgesia (Tramadol), pre and postoperative pulmonary function test {(Forced Expiratory Volume (FEV)1, Forced Vital Capacity (FVC), FEV1/FVC, Peak Expiratory Flow Rate (PEFR)} and complications from start of infusion till 24 hours in the postoperative period. RESULTS: Both the techniques were effective in relieving pain but pain relief was significantly better with epidural. Postoperatively, HR, SpO2, P/F ratio and PaCO2 were comparable between group E and P. There was significant decline in FeV1, FVC, FeV1/FVC and PEFR in postoperative period as compared to preoperative value in both the groups. Hypotension and bradycardia were more in group E. CONCLUSION: Both the techniques, continuous thoracic epidural block and continuous thoracic paravertebral block were effective for post-thoracotomy pain relief; however, epidural block provides better pain relief. The incidence of sympatholytic complications was more in epidural group. The effect on respiratory mechanics was equivalent. Hence, paravertebral block can be used in post thoracotomy pain relief in those patients where thoracic epidural is contraindicated.

7.
J Clin Diagn Res ; 10(6): UC05-8, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27504383

ABSTRACT

INTRODUCTION: Buprenorphine is a semi-synthetic derivative of thebaine; its low concentration is sufficient to provide effective pain relief. AIM: To evaluate the efficacy of transdermal buprenorphine patch in postoperative pain management. MATERIALS AND METHODS: After ethical approval and taking informed consent from the patients, they were randomized into three groups (n=30 in each group) using a computer generated random number table. Group A: placebo patch; Group B: buprenorphine (10mg) patch and Group C: buprenorphine (20mg) patch. Haemodynamic and analgesic effects were compared by using analysis of variance (ANOVA) followed by Turkey's post hoc test. The proportion of side effects was compared using the Chi-square test. RESULTS: Haemodynamic changes were not statistically different in all the three groups A, B and C, whereas at the end of surgery VAS score of Group A subjects was significantly higher (4.93±0.98) as compared to Group B (1.73±0.64) and Group C (1.40±0.50). On 2(nd) postoperative day, no pain was reported by the Group C patients and on 4(th) day after surgery, no pain was reported by Group B patients. CONCLUSION: The transdermal buprenorphine patch (20mg) was effective in attenuating postoperative pain, maintaining haemodynamic stability requiring no rescue analgesia, with fewer postoperative rescue analgesic requirements in low dose of buprenorphine patch (10mg) group.

8.
J Clin Diagn Res ; 10(1): UC05-8, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26894151

ABSTRACT

INTRODUCTION: Multimodal analgesia includes regional anaesthesia in the form of nerve block may improve recovery along with optimal rehabilitation and early resumption of day-to-day activity following major surgery. Conventional general anaesthesia consists of premedication, induction, intubation and maintenance. AIM: The aim of the study is to compare the multimodal versus conventional approach in oral cancer surgery. MATERIALS AND METHODS: The patients were randomly allocated into three groups, 30 patients in each group using the computer generated random table to one of the following groups: Group A: Fentanyl 1 µg/kg, Group B: Fentanyl 1 µg/kg + bupivacaine local infiltration, Group C: Fentanyl 1 µg/kg + bupivacaine local infiltration + Dexemedetomidine infusion (Loading 0.5 µg/kg, Maintenance 0.2µg/kg/hr). RESULTS: No significant (p>0.05) difference was found in mean arterial pressure and heart rate at different time intervals among the groups. The VAS was lower in Group C than Group B and A. The ramsay sedation scale was higher in Group C than Group B and A. The rescue analgesic for 24 hour was lower in Group C than Group B and A. The time of first time analgesia requirement was significantly (p=0.001) higher in Group C than Group B and A. The rescue analgesic was significantly (p=0.001) lower in Group C (39.29±19.67) than Group B (68.33±18.49) and A (160.83±35.16). CONCLUSION: Multimodal analgesia has beneficial haemodynamic effects during oral cancer surgery with reliable postoperative analgesia and sedation and less postoperative complication. Dose of drugs used in our study is not associated with any major adverse effect.

9.
J Clin Diagn Res ; 8(8): GC09-13, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25302210

ABSTRACT

BACKGROUND: Feeling of pain is one of the most important emotional determinants which dominate the perception of females who undergo the process of labour and delivery. Patient controlled epidural labour analgesia (PCEA) is convenient and safer technique for this purpose. Very few studies compared clonidine and fentanyl with ropivacaine in labour analgesia in past. This study was undertaken to compare fentanyl and clonidine in PCEA. AIMS: To compare low concentration ropivacaine with or without fentanyl or clonidine for labour analgesia and its effect on maternal and foetal safety. SETTINGS AND DESIGN: Prospective, double blind, randomized, comparative study. MATERIALS AND METHODS: Ninety primegravida in labour were divided into three groups (n=30) and patient controlled epidural labour analgesia was given to them: Initial bolus of 10ml of ropivacaine 0.125% in Group I; with fentanyl 2 µg/ml in Group II and with clonidine 1µg/kg in Group III. Subsequently each group received ropivacaine 0.125% through patient controlled epidural analgesia (PCEA) as background infusion of 5 ml/hr with lockout interval time of 10min and subsequent bolus of 5ml. Hemodynamic parameters, sensory level, motor block and pain relief were noted. Total analgesic dose of local anaesthetic and feto-maternal adverse effects were also recorded. RESULTS: At baseline, groups were matched demographically, hemodynamically as well as for intensity of pain. There was a statistically significant decrease in hemodynamic parameters from baseline in all groups with maximum reduction in group III. A significant difference among groups in VAS was observed at zero min and from 120min till 240min intervals and lowest values were in Group III. No significant difference was observed among the groups for mode of delivery and expulsive efforts. Total analgesic dose and PCA bolus requirement was maximum in Group I and minimum in Group III and the difference was statistically significant among groups. Six (20%) patients had shivering in Group II and hypotension was recorded in only 1 (3.3%) patient of Group III. CONCLUSION: Ropivacaine 0.125% was effective in decreasing labour pain without any motor blockade. Clonidine 1µg/kg was superior to fentanyl 2µg/ml as an adjuvant in PCEA for labour without any significant feto-maternal adverse effects.

10.
Mutat Res ; 753(1): 7-23, 2013.
Article in English | MEDLINE | ID: mdl-23370482

ABSTRACT

Matrix metalloproteinase (MMP) comprises a family of zinc-dependent endopeptidases that degrade various components of the extracellular matrix (ECM) and basement membrane. MMPs are involved in solid and hematological malignancy through modification of cell growth, activation of cancer cells and modulation of immune functions. Several polymorphisms of different MMPs such as MMP-1 (-1607 1G/2G), MMP-2 (-1306 C/T), MMP-3 (-1171 5A/6A) & MMP-9 (-1562 C/T) and their expression levels have been well documented in different types of solid cancer. These polymorphic variations were found to be associated with angiogenesis, cancer progression, invasion and metastasis. There is paucity of data available in the field of hematological malignancies. Hence the field of matrix biology of hematological malignancies is an area of active exploration. A number of MMP inhibitors (MMPIs) have been developed for the cancer treatment. The most extensively studied classes of MMP inhibitors include Batimastat, Marismastat, Salimatat, Prinomastat and Tanomastat. However, their efficacy and action have not been confirmed and more data is required. The application of one or more selective targeted MMPIs in combination with conventional anti-leukemic treatment may represent a positive approach in combat against hematopoietic malignancies. Balance of MMPs and TIMPs is altered in different malignancies and biochemical pathways. These alternations will add another dimension in the matrix biology of both solid tumor and leukemia. MMP and TIMP singly and in combination are increasingly being recognized as an important player in basic cellular biology. Exploration and exploitation of MMP and TIMP balance in various malignant and nonmalignant lesions is going to be one of the most interesting facets of future use of this system for human health care.


Subject(s)
Antineoplastic Agents/therapeutic use , Hematologic Neoplasms/drug therapy , Matrix Metalloproteinase Inhibitors/therapeutic use , Matrix Metalloproteinases/chemistry , Neoplasms/drug therapy , Animals , Hematologic Neoplasms/enzymology , Humans , Matrix Metalloproteinases/metabolism , Neoplasms/enzymology
11.
Biomarkers ; 16(7): 577-86, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21958210

ABSTRACT

The aim of this study was to explore the association of MMP-2 (-1306 C/T and -168 G/T) and MMP-9 (-1562 C/T) promoter polymorphisms in oral submucous fibrosis (OSMF) and head and neck squamous cell carcinoma (HNSCC) cases. These SNP were genotyped by PCR-RFLP. Total of 1260 individuals were recruited, of which 412 OSMF, 422 HNSCC and 426 were controls. In HNSCC, MMP-2 (-1306 C/T) and MMP-9 (-1562C/T) polymorphism, T allele showed strong association (p < 0.00 and p < 0.01) as compared to healthy control respectively, but not in case of OSMF and showed significant association with increasing progression of clinico-pathological grading. We concluded that SNPs in the MMP-2 and -9 promoter region may be associated with susceptibility to HNSCC not in OSMF.


Subject(s)
Carcinoma, Squamous Cell/genetics , Head and Neck Neoplasms/genetics , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 9/genetics , Oral Submucous Fibrosis/genetics , Polymorphism, Single Nucleotide , Promoter Regions, Genetic/genetics , Adult , Aged , Chi-Square Distribution , Female , Gene Frequency , Genetic Predisposition to Disease/genetics , Genotype , Humans , India , Male , Middle Aged , Odds Ratio , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length
12.
Virol J ; 7: 253, 2010 Sep 23.
Article in English | MEDLINE | ID: mdl-20863370

ABSTRACT

BACKGROUND: Oral malignancy is a major global health problem. Besides the main risk factors of tobacco, smoking and alcohol, infection by human papillomavirus (HPV) and genetic alterations are likely to play an important role in these lesions. The purpose of this study was to compare the efficacy of HC-II assay and PCR for the detection of specific HPV type (HPV 16 E6) in OSMF and OSCC cases as well as find out the prevalence of the high risk HPV (HR-HPV) in these lesions. METHODS AND MATERIALS: Four hundred and thirty patients of the potentially malignant and malignant oral lesions were taken from the Department of Otorhinolaryngology, Moti Lal Nehru Medical College, Allahabad, India from Sept 2007-March 2010. Of which 208 cases were oral submucous fibrosis (OSMF) and 222 cases were oral squamous cell carcinoma (OSCC). The HC-II assay and PCR were used for the detection of HR-HPV DNA. RESULT: The overall prevalence of HR-HPV 16 E6 DNA positivity was nearly 26% by PCR and 27.4% by the HC-II assay in case of potentially malignant disorder of the oral lesions such as OSMF. However, in case of malignant oral lesions such as OSCC, 32.4% HPV 16 E6 positive by PCR and 31.4% by the HC-II assay. In case of OSMF, the two test gave concordant result for 42 positive samples and 154 negative samples, with an overall level of agreement of 85.4% (Cohen's kappa = 66.83%, 95% CI 0.553-0.783). The sensitivity and specificity of the test were 73.7% and 92.05% (p < 0.00). In case of OSCC, the two test gave concordant result for 61 positive samples and 152 negative samples, with an overall level of agreement of 88.3% (Cohen's kappa = 79.29, 95% CI 0.769-0.939) and the sensitivity and specificity of the test were 87.14% and 92.76% (p < 0.00). CONCLUSION: This study concluded that slight difference was found between the positivity rate of HR-HPV infection detected by the HC-II and PCR assay in OSMF and OSCC cases and the HC II assay seemed to have better sensitivity in case of OSCC.


Subject(s)
Carcinoma, Squamous Cell/virology , Mouth Neoplasms/virology , Nucleic Acid Hybridization/methods , Oral Submucous Fibrosis/virology , Papillomaviridae/isolation & purification , Papillomavirus Infections/diagnosis , Polymerase Chain Reaction/methods , Adult , Aged , DNA, Viral/genetics , DNA, Viral/isolation & purification , Female , Humans , India , Male , Middle Aged , Papillomaviridae/genetics , Sensitivity and Specificity , Virology/methods
13.
Biomarkers ; 15(8): 684-92, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20860530

ABSTRACT

Matrix metalloproteinases (MMP) are a family of zinc-dependent proteases that degrade the entire component of the extracellular matrix. Our study explores the association of the MMP1 gene promoter (-1607 1G/2G) polymorphisms in oral submucous fibrosis (OSMF) and head and neck squamous cell carcinoma (HNSCC) in an Indian population. The MMP1 single-nucleotide polymorphism (SNP) was genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis in 412 patients with OSMF, 422 with HNSCC and 426 controls. Our results showed that the frequency of 1G/2G or 2G/2G promoter genotypes having the 2G allele is associated with higher enzymatic activity and significantly increases in OSMF (p<0.001) and HNSCC cases (p<0.00). In this study, results concluded that SNPs in the MMP1 promoter region may be associated with susceptibility to OSMF as well as HNSCC in an Indian population and addiction habits such as areca nut chewing and alcohol abuse may enhance the expression of the 2G allele of MMP1 genes in OSMF and HNSCC cases.


Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/genetics , Head and Neck Neoplasms/genetics , Matrix Metalloproteinase 1/genetics , Oral Submucous Fibrosis/genetics , Polymorphism, Single Nucleotide , Promoter Regions, Genetic , Adult , Base Sequence , Case-Control Studies , DNA Primers , Female , Humans , India , Male , Middle Aged , Polymerase Chain Reaction
14.
Asian Pac J Cancer Prev ; 11(1): 257-60, 2010.
Article in English | MEDLINE | ID: mdl-20593967

ABSTRACT

OBJECTIVE: The objective of this study is to analyze cases of oral submucous fibrosis (OSMF) Grade I, II, III and IV morphometrically with regard to epithelium, vasculature and fibrosis and determine any correlation with histological grading after Pindborg and Sirsat. MATERIALS AND METHODS: Eighty three oral submucous fibrosis cases were analyzed morpometrically using an interactive image analysis system in the Department of Pathology, M.L.N Medical College, Allahabad, U.P, India. Paraffin embedded sections of 3-4 microm thickness were stained with hematoxylin/eosin, Van Gieson's picric acid and acid fuchsin stain and Masson's trichrome stains. Image analysis was performed with specific software (Image Pro Plus 6.0) and data obtained were finally transported to Excel sheets for calculation of average values for each parameter. RESULTS: With the grading criteria applied, 9 cases of OSMF were grade I, 32 grade II, 39 grade III and 3 grade IV. Clinical trismus was most frequent in Grade IV followed by Grade III, II and I respectively. OSMF Grade I cases did not show any measurable amount of collagenization, whereas it showed a significant increase with OSMF I and II grades [Pearson's chi2 test= 85.72; p= 0.051] and OSMF-III and IV [Pearson's chi2 test=188.74; p<0.001]. Numbers of endothelial cells per low power field consistently decreased with the increasing grade. CONCLUSIONS: We concluded that mean blood vessel area and the mean vessel diameter showed a marked increase in grade II and a marker decrease in grade IV and the grade III, collagen thickness (mum) increases according to increasing grade while density of endothelial cells decreases.


Subject(s)
Head and Neck Neoplasms/pathology , Image Processing, Computer-Assisted , Oral Submucous Fibrosis/pathology , Adolescent , Adult , Female , Humans , Male , Middle Aged , Neoplasm Staging , Prognosis , Young Adult
15.
J Biomed Sci ; 17: 10, 2010 Feb 15.
Article in English | MEDLINE | ID: mdl-20152059

ABSTRACT

Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases that are capable of cleaving all extra cellular matrix (ECM) substrates. Degradation of matrix is a key event in progression, invasion and metastasis of potentially malignant and malignant lesions of the head and neck. It might have an important polymorphic association at the promoter regions of several MMPs such as MMP-1 (-1607 1G/2G), MMP-2 (-1306 C/T), MMP-3 (-1171 5A/6A), MMP-9 (-1562 C/T) and TIMP-2 (-418 G/C or C/C). Tissue inhibitors of metalloproteinases (TIMPs) are naturally occurring inhibitors of MMPs, which inhibit the activity of MMPs and control the breakdown of ECM. Currently, many MMP inhibitors (MMPIs) are under development for treating different malignancies. Useful markers associated with molecular aggressiveness might have a role in prognostication of malignancies and to better recognize patient groups that need more antagonistic treatment options. Furthermore, the introduction of novel prognostic markers may also promote exclusively new treatment possibilities, and there is an obvious need to identify markers that could be used as selection criteria for novel therapies. The objective of this review is to discuss the molecular functions and polymorphic association of MMPs and TIMPs and the possible therapeutic aspects of these proteinases in potentially malignant and malignant head and neck lesions. So far, no promising drug target therapy has been developed for MMPs in the lesions of this region. In conclusion, further research is required for the development of their potential diagnostic and therapeutic possibilities.


Subject(s)
Head and Neck Neoplasms/genetics , Matrix Metalloproteinases/genetics , Polymorphism, Genetic , Tissue Inhibitor of Metalloproteinases/genetics , Animals , Gene Expression Regulation, Neoplastic , Genetic Predisposition to Disease , Humans , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 3/genetics , Matrix Metalloproteinase 9/genetics , Neovascularization, Pathologic/genetics , Tissue Inhibitor of Metalloproteinase-1/genetics , Tissue Inhibitor of Metalloproteinase-2/genetics
16.
J Oral Pathol Med ; 39(6): 460-4, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20070487

ABSTRACT

BACKGROUND: Oral submucous fibrosis (OSMF) is a widely prevalent, potentially malignant disorder of the oral cavity in the Indian subcontinent. Areca nut has been incriminated as the main causative factor. However, other factors, including viruses may also play a role in the initiation/development of these lesions. This study was designed to assess the correlation of addictive factors, human papilloma virus infection and histopathology of OSMF. METHODS: One hundred and thirteen cases of OSMF were studied. Demographic information of each patient, including the patient's age, sex, addiction habits and histopathological grading was obtained. Presence of high-risk human papilloma virus (HR-HPV) DNA was detected using the Hybrid Capture II assay. RESULTS: Of 105 cases finally included in the study, 33 (31.4%) patients were found to be positive for HR-HPV, while 72 (68.6%) were negative. A total of 52/105 (49.5%) patients chewed areca nut, of whom 18 (34.6%) patients were found to be positive and 34 (63.5%) were negative (P = 0.08). A total of 18/105 (17.1%) patients were addicted to smoking, of whom five (27.7%) were positive (0.69). Only one (11.1%) patient, who was only habituated to alcohol, was positive (1.08). Of the 105 patients 26 (24.7%) chewed as well as smoked tobacco, of whom, nine (34.6%) were positive and 17(65.3%) were negative (P = 0.67). Thus, there was no significant association between the various addiction habits and the presence of HR-HPV. On correlating the various histopathological grades of the disease with HR-HPV positivity a Pearson correlation of 0.053 was obtained (P = 0.588). Thus, again no significant correlation was observed between the different histopathological grades and HR-HPV positivity. CONCLUSION: In conclusion, it was found that there is neither significant correlation between HR-HPV infection and the various addiction habits nor with the different histopathological grades of the disease. To the best of our knowledge, a study of these different factors has never been attempted before in patients with OSMF.


Subject(s)
Areca/adverse effects , Oral Submucous Fibrosis/etiology , Papillomavirus Infections/complications , Smoking/adverse effects , Adult , Alcohol Drinking/adverse effects , Case-Control Studies , DNA, Viral/analysis , Female , Humans , Male , Middle Aged , Oral Submucous Fibrosis/pathology , Viral Load , Young Adult
17.
Lipids Health Dis ; 8: 29, 2009 Jul 24.
Article in English | MEDLINE | ID: mdl-19630946

ABSTRACT

BACKGROUND: Changes in lipid profile have long been associated with malignancies as lipids play a key role in maintenance of cell integrity. This study evaluated the alterations in extended lipid profile in untreated patients of oral submucous fibrosis (OSMF) and studied the correlation between lipid levels with tobacco consumption. MATERIALS AND METHODS: In this hospital-based study, 65 clinically diagnosed and histopathologically proven patients of OSMF and 42 age and sex matched controls were studied. In these samples serum lipids including: (i) Total cholesterol, (ii) LDL cholesterol (LDLC), (iii) HDL cholesterol (HDLC) (iv) VLDL cholesterol (VLDLC) (v) triglycerides (vi) Apo-A1 (viii) Apo-B and (viii) LPa were analyzed. RESULTS: A significant decrease in plasma total cholesterol, HDLC and Apo-A1 was observed in patients with OSMF as compared to the controls. Thus an inverse relationship between plasma lipid levels and patients was found in OSMF. CONCLUSION: The lower levels of plasma cholesterol and other lipid constituents in patients might be due to their increased utilization. The findings strongly warrant an in-depth study of alterations in plasma lipid profile in patients with oral precancerous conditions.


Subject(s)
Lipids/blood , Oral Submucous Fibrosis/blood , Substance-Related Disorders/blood , Adolescent , Adult , Apolipoprotein A-I/blood , Apolipoproteins B/blood , Case-Control Studies , Child , Chronic Disease , Female , Humans , India , Lipoprotein(a)/blood , Male , Middle Aged , Oral Submucous Fibrosis/etiology , Precancerous Conditions/blood , Precancerous Conditions/etiology , Smoking , Young Adult
18.
Head Neck Oncol ; 1: 22, 2009 Jun 25.
Article in English | MEDLINE | ID: mdl-19555477

ABSTRACT

Head and neck malignancies are characterized by a multiphasic and multifactorial etiopathogenesis. Tobacco and alcohol consumption are the most common risk factors for head and neck malignancy. Other factors, including DNA viruses, especially human papilloma virus (HPV), may also play a role in the initiation or development of these lesions. The pathways of HPV transmission in the head and neck mucosal lesions include oral-genital contact, more than one sexual partner and perinatal transmission of HPV to the neonatal child. The increase in prevalence of HPV infection in these lesions may be due to wider acceptance of oral sex among teenagers and adults as this is perceived to be a form of safe sex. The prevalence of HPV in benign lesions as well as malignancies has been assessed by many techniques. Among these, the polymerase chain reaction is the most sensitive method. Review of literature reveals that HPV may be a risk factor for malignancies, but not in all cases. For confirmation of the role of HPV in head and neck squamous cell carcinoma, large population studies are necessary in an assortment of clinical settings. Prophylactic vaccination against high-risk HPV types eventually may prevent a significant number of cervical carcinomas. Of the two vaccines currently available, Gardasil (Merck & Co., Inc.) protects against HPV types 6, 11, 16 and 18, while the other vaccine, Cervarix (GlaxoSmithKline, Rixensart, Belgium) protects against HPV types 16 and 18 only. However, the HPV vaccine has, to the best of our knowledge, not been tried in head and neck carcinoma. The role of HPV in etiopathogenesis, prevalence in benign and malignant lesions of this area and vaccination strategies are briefly reviewed here.


Subject(s)
Head and Neck Neoplasms/virology , Papillomaviridae/isolation & purification , Gene Expression Profiling , Head and Neck Neoplasms/etiology , Head and Neck Neoplasms/pathology , Humans , Immunohistochemistry , In Situ Hybridization , Papillomavirus Vaccines/immunology , Polymerase Chain Reaction
19.
Head Neck Oncol ; 1: 10, 2009 May 02.
Article in English | MEDLINE | ID: mdl-19409103

ABSTRACT

BACKGROUND: Oral submucous fibrosis is a common oral health problem in India. This study was conducted to correlate the histopathological diagnosis with habits and clinical findings in patients suffering from oral submucous fibrosis (OSF). METHODS: Patients suffering from oral submucous fibrosis from the Departments of Otorhinolaryngology and Pathology, Moti Lal Nehru Medical College, Allahabad, India were studied from 2004-2008. Detailed information was gathered in a pretested proforma. Emphasis was given to the various addictions, clinical findings and histological examination was done. RESULTS: Two hundred and thirty nine patients were studied, yielding a male to female ratio of 6.8:1. Maximum patients were in the 21-30 years age group with a marked male predominance. Of these, 197 (82.4%) patients chewed areca nut/dohra, 14 (5.8%) were smokers and 2 (0.8%) patients were habituated to alcohol. 89 (37.2%) patients reported difficulty in opening of the mouth (trismus). 51 (57.4%) patients were found to have stage II (2-3 cm) trismus while rest had stage I and III. The buccal mucosa was found to be the most commonly involved site. On the basis of histopathological examination, 52 (21.7%) were classified as OSF grade I, 75 (31.3%) patients as grade II and 112 (46.8%) had grade III disease. CONCLUSION: The widespread habit of chewing dohra/paan masala is a major risk factor of OSF, especially in the younger age group. In this study, an increase in histopathological grading was found with severity and duration of addiction habit. However no significant correlation was found between clinical staging and histopathological grading.


Subject(s)
Areca/adverse effects , Oral Submucous Fibrosis/etiology , Oral Submucous Fibrosis/pathology , Adult , Aged , Female , Humans , Male , Middle Aged , Mouth Mucosa/pathology , Oral Submucous Fibrosis/therapy , Risk Factors , Smoking/adverse effects
20.
Asian Pac J Cancer Prev ; 10(6): 1173-5, 2009.
Article in English | MEDLINE | ID: mdl-20192607

ABSTRACT

OBJECTIVE: The present study was designed to identify a core promotor mutation in the HBV genome in patients suffering from HBV related chronic liver disease. MATERIALS AND METHODS: 154 chronic liver disease patients were selected for study of DNA extracted using a pure viral DNA extraction kit. The core promoter mutation was detected by the polymerase chain reaction- based restriction fragment length polymorphism (PCR-RFLP) method, using the Sau 3AI restriction enzyme to see if cleavage would occur at this specific site. RESULTS: Among the total of 154, 78 patients were found positive for HBsAg and 71 samples were found to be positive for HBV DNA by first round PCR. The over all prevalence of core mutant was 51(71%) in the 71 patients. 11 (68.8%) of 16 patients, excluding 1 patients with mixed type mutation was detected in inactive HBsAg carriers, 39 (81.3%), excluding 2 patients with mixed type was detected in chronic hepatitis B, and 4/7 (57%) in patients with liver cirrhosis were found. CONCLUSION: Our study concluded that the prevalence of the core promoter mutation in the BCP region was higher in the patients with chronic hepatitis B than in liver cirrhosis and HBsAg carriers. The Sau3AI assay, which is much more convenient than sequencing, was shown to be useful for the detection of the core promoter mutant in an extensive number of clinical samples. Monitoring and detection of HBV variants by PCR-RFLP in chronic infection may improve the management of these patients.


Subject(s)
DNA, Viral/analysis , Hepatitis B Core Antigens/genetics , Hepatitis B virus/genetics , Hepatitis B, Chronic/genetics , Mutation/genetics , Promoter Regions, Genetic , Viral Core Proteins/genetics , Female , Humans , India , Male , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length
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