Arif M.,Molecular Biology and Genetics Unit |
Vedamurthy B.M.,Molecular Biology and Genetics Unit |
Choudhari R.,Molecular Biology and Genetics Unit |
Ostwal Y.B.,Molecular Biology and Genetics Unit |
And 3 more authors.
Chemistry and Biology | Year: 2010
Altered histone acetylation is associated with several diseases, including cancer. We report here that, unlike in most cancers, histones are found to be highly hyperacetylated in oral squamous cell carcinoma (OSCC; oral cancer) patient samples. Mechanistically, overexpression, as well as enhanced autoacetylation, of p300 induced by nucleophosmin (NPM1) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) causes the hyperacetylation, which is nitric oxide (NO) signal dependent. Inhibition of the histone acetyltransferase (HAT) activity of p300 by a water-soluble, small molecule inhibitor, Hydrazinocurcumin (CTK7A), substantially reduced the xenografted oral tumor growth in mice. These results, therefore, not only establish an epigenetic target for oral cancer, but also implicate a HAT inhibitor (HATi) as a potential therapeutic molecule. © 2010 Elsevier Ltd.
Sanjay P.,Auckland City Hospital |
Sanjay P.,Ninewells Hospital and Medical School |
Takaori K.,Kyoto University |
Govil S.,Bangalore Institute of Oncology |
And 3 more authors.
British Journal of Surgery | Year: 2012
Background: The technique of pancreatoduodenectomy (PD) has evolved. Previously, non-resectability was determined by involvement of the portal vein-superior mesenteric vein. Because venous resection can be achieved safely and with greater awareness of the prognostic significance of the status of the posteromedial resection margin, non-resectability is now determined by involvement of the superior mesenteric artery (SMA). This change, with a need for early determination of resectability before an irreversible step, has promoted the development of an 'artery-first' approach. The aim of this study was to review, and illustrate, this approach. Methods: An electronic search was performed on MEDLINE, Embase and PubMed databases from 1960 to 2011 using both medical subject headings and truncated word searches to identify all published articles that related to this topic. Results: The search revealed six different surgical approaches that can be considered as 'artery first'. These involved approaching the SMA from the retroperitoneum (posterior approach), the uncinate process (medial uncinate approach), the infracolic region medial to the duodenojejunal flexure (inferior infracolic or mesenteric approach), the infracolic retroperitoneum lateral to the duodenojenunal flexure (left posterior approach), the supracolic region (inferior supracolic approach) and through the lesser sac (superior approach). Conclusion: The six approaches described provide a range of options for the early determination of arterial involvement, depending on the location and size of the tumour, and before the 'point of no return'. Whether these approaches will achieve an increase in the proportion of patients with negative margins, improve locoregional control and increase long-term survival has yet to be determined. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.
Venkatesh T.,Indian Institute of Science |
Nagashri M.N.,Indian Institute of Science |
Swamy S.S.,Bangalore Institute of Oncology |
Mohiyuddin S.M.A.,lappa Hospital And Research Center |
And 2 more authors.
PLoS ONE | Year: 2013
Mutations in the MCPH1 (microcephalin 1) gene, located at chromosome 8p23.1, result in two autosomal recessive disorders: primary microcephaly and premature chromosome condensation syndrome. MCPH1 has also been shown to be downregulated in breast, prostate and ovarian cancers, and mutated in 1/10 breast and 5/41 endometrial tumors, suggesting that it could also function as a tumor suppressor (TS) gene. To test the possibility of MCPH1 as a TS gene, we first performed LOH study in a panel of 81 matched normal oral tissues and oral squamous cell carcinoma (OSCC) samples, and observed that 14/71 (19.72%) informative samples showed LOH, a hallmark of TS genes. Three protein truncating mutations were identified in 1/15 OSCC samples and 2/5 cancer cell lines. MCPH1 was downregulated at both the transcript and protein levels in 21/41 (51.22%) and 19/25 (76%) OSCC samples respectively. A low level of MCPH1 promoter methylation was also observed in 4/40 (10%) tumor samples. We further observed that overexpression of MCPH1 decreased cellular proliferation, anchorage-independent growth in soft agar, cell invasion and tumor size in nude mice, indicating its tumor suppressive function. Using bioinformatic approaches and luciferase assay, we showed that the 3′-UTR of MCPH1 harbors two non-overlapping functional seed regions for miR-27a which negatively regulated its level. The expression level of miR-27a negatively correlated with the MCPH1 protein level in OSCC. Our study indicates for the first time that, in addition to its role in brain development, MCPH1 also functions as a tumor suppressor gene and is regulated by miR-27a. © 2013 Venkatesh et al.
Govil S.,Bangalore Institute of Oncology
Hepato-Gastroenterology | Year: 2014
Ante-situm liver resection under hypothermic total vascular exclusion is used to resect large tumours that involve the hepatic veins close to the vena cava or the cava itself. This procedure traditionally requires venovenous bypass when it is necessary to clamp the cava, or portocaval shunt when caval continuity is maintained by piggyback dissection of the liver. We present a technique of ante-situm liver resection, operating on one side of the liver at a time while maintaining prograde portal flow through the opposite side of the liver, thereby avoiding venovenous bypass, portacaval shunt and portal vein reconstruction. © H.G.E. Update Medical Publishing S.A.
Sellakumar P.,Bangalore Institute of Oncology |
James Jebaseelan Samuel E.,Vellore Institute of Technology
Radiation Measurements | Year: 2010
The normoxic polymer gel dosimeter evaluated with X-Ray computed tomography has emerged as a promising tool for measuring the dose delivered during radiotherapy in three dimensions. This study presents the dependence of PAGAT normoxic polymer gel sensitivity to different photon and electron energies. PAGAT polymer gel was prepared under normal atmospheric condition and irradiated with different photon energies of 1.25 MeV from Co-60 and 6 MV and 15 MV from linear accelerator and electron energies of 6, 9, 12, 15, 18 and 21 MeV from linear accelerator. Evaluation of dosimeter was performed with an X-Ray CT scanner. Images were acquired with optimum scanning protocols to reduce the signal-to-noise ratio. The averaged image was subtracted from the unirradiated polymer gel image for background. Central axis depth dose (PDD) curves obtained for each energy and polymer gel dosimeter measurements were in good agreement with diode and film measurements. Hounsfield (HU) - dose response curve for each photon and electron energy were derived from the PDD curve obtained from the gel dosimeter measurements. From the study it was clear that the HU-dose response curve was linear in the region 1-10 Gy. The dosimeter sensitivity was defined as a slope of these linear HU-dose response curves and found that the sensitivity of polymer gel decreases with increase in both photon and electron energies. This trend in dependence of PAGAT gel dosimeter sensitivity to different photon and electron energies was not dosimetrically significant. However, to evaluate the test phantom exposed with one energy using the calibration curve derived at another energy can produce clinically significant error. Crown Copyright © 2009.
Vallath N.,Bangalore Institute of Oncology
Indian Journal of Palliative Care | Year: 2010
Chronic pain is multi-dimensional. At the physical level itself, beyond the nociceptive pathway, there is hyper arousal state of the components of the nervous system, which negatively influences tension component of the muscles, patterns of breathing, energy levels and mindset, all of which exacerbate the distress and affect the quality of life of the individual and family. Beginning with the physical body, Yoga eventually influences all aspects of the person: vital, mental, emotional, intellectual and spiritual. It offers various levels and approaches to relax, energize, remodel and strengthen body and psyche. The asanas and pranayama harmonize the physiological system and initiate a "relaxation response" in the neuro endocrinal system. This consists of decreased metabolism, quieter breathing, stable blood pressure, reduced muscle tension, lower heart rate and slow brain wave pattern. As the neural discharge pattern gets modulated, hyper arousal of the nervous system and the static load on postural muscle come down. The function of viscera improves with the sense of relaxation and sleep gets deeper and sustained; fatigue diminishes. Several subtle level notional corrections can happen in case the subject meditates and that changes the context of the disease, pain and the meaning of life. Meditation and pranayama, along with relaxing asanas, can help individuals deal with the emotional aspects of chronic pain, reduce anxiety and depression effectively and improve the quality of life perceived.
Pradhan S.,Indian Institute of Science |
Nagashri M.N.,Indian Institute of Science |
Gopinath K.S.,Bangalore Institute of Oncology |
Kumar A.,Indian Institute of Science
PLoS ONE | Year: 2011
Oral Squamous Cell Carcinoma (OSCC) has a very flagitious treatment regime. A prodrug approach is thought to aid in targeting chemotherapy. CYP1B1, a member of cytochrome P450 family, has been implicated in chemical carcinogenesis. There exists a general accordance that this protein is overexpressed in a variety of cancers, making it an ideal candidate for a prodrug therapy. The activation of the prodrug facilitated by CYP1B1 would enable the targeting of chemotherapy to tumor tissues in which CYP1B1 is specifically overexpressed as a result reducing the non-specific side effects that the current chemotherapy elicits. This study was aimed at validating the use of CYP1B1 as a target for the prodrug therapy in OSCC. The expression profile of CYP1B1 was analysed in a panel of 51 OSCC tumors, their corresponding normal tissues, an epithelial dysplasia lesion and its matched normal tissue by qRT-PCR, Western blotting and Immunohistochemistry. CYP1B1 was found to be downregulated in 77.78% (28/36) tumor tissues in comparison to their corresponding normal tissues as well as in the epithelial dysplasia lesion compared to its matched normal tissue at the transcriptional level, and in 92.86% (26/28) of tumor tissues at the protein level. This report therefore clearly demonstrates the downregulation of CYP1B1 at the transcriptional and translational levels in tumor tissues in comparison to their corresponding normal tissues. These observations indicate that caution should be observed as this therapy may not be applicable universally to all cancers and also suggest the possibility of a prophylactic therapy for oral cancer. © 2011 Pradhan et al.
Tiwari R.M.,Bangalore Institute of Oncology
Indian Journal of Surgical Oncology | Year: 2010
In the surgical management of T3-T4 carcinoma of the maxillary antrum, involvement of the roof and/or erosion of the orbital floor, raises the possibility of the sacrifice of the orbital contents. While it is evident that the eyeball has to be sacrificed in the presence of gross disease, the indications when it can be preserved are not clear. Radiological assessment requires a minimum thickness of 4mm of the tissue. Standard anatomical texts describe the bony orbital floor and the orbital periosteum. In 1998 this author for the first time described a distinct fascial layer which encapsulates the orbital fat and termed it Periorbital Fascia. The purpose of this article is to draw attention to this anatomical structure and discuss the precise indications when the eyeball may be sacrificed or preserved. The conclusions are based on the experience with eighty two total maxillectomies for cancer performed over a period of 30 years. In the opinion of this author the following conclusions can be drawn. First, the orbital fat does not rest on the orbital periosteum as shown in anatomical texts, but is enclosed in a thin independent fascial layer termed the periorbital fascia. Secondly, in the event of malignant disease eroding the orbital roof, what is crucial is to know whether the orbital periosteum is involved and to know as to whether the disease process has reached the orbital surface of the periosteum. In case the disease is limited to the under surface of the orbital periosteum, the eyeball may still be preserved by a careful dissection between the periosteum and the periorbital fascia. © 2010 Indian Association of Surgical Oncology.
Govil S.,Bangalore Institute of Oncology
Indian Journal of Gastroenterology | Year: 2013
Despite progress in the field of liver surgery, centrally located tumors that involve the inferior vena cava or the hepatic veins adjacent to the vena cava are a technical challenge. These patients usually need to be operated upon under total vascular exclusion to prevent massive blood loss. The duration of vascular exclusion often exceeds the maximum permissible warm ischemia time tolerated by the liver, particularly when vascular reconstructions are necessary as part of the resection. The role of hypothermia as an adjunct to total vascular exclusion (TVE) was first introduced in 1974 but is used infrequently. A clearer understanding of this technique might allow clinicians to consider tumors in these awkward situations for resection. Additional techniques that may extend the benefits of hypothermic TVE are ante situm and ex vivo resections with autotransplantation. This review discusses the role of hypothermic TVE in the modern management of liver tumors. © 2013 Indian Society of Gastroenterology.
Govil S.,Bangalore Institute of Oncology
Indian Journal of Gastroenterology | Year: 2014
Resection and reimplantation of the superior mesenteric artery (SMA) as part of a pancreaticoduodenal resection for cancer is rarely performed even in high-volume centers because of the risks inherent in this procedure and the perceived lack of oncological benefit associated with arterial resection during pancreaticoduodenectomy. The role of arterial resection during pancreaticoduodenectomy has recently been reevaluated, and this procedure may be of greater benefit than previously believed in selected patients. It also has a definite role when necessary to resect low-grade pancreatic and peripancreatic malignancies or to salvage intraoperative injury to the SMA. This small case series presents the authors experience with this procedure. © 2013 Indian Society of Gastroenterology.