Kidwai Memorial Institute of Oncology

Bangalore, India

Kidwai Memorial Institute of Oncology

Bangalore, India
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Asati V.,Guru Ghasidas University | Bharti S.K.,Guru Ghasidas University | Asati V.,Kidwai Memorial Institute of Oncology | Budhwani A.K.,Institute of Pharmacy
Current Pharmaceutical Design | Year: 2016

Background: PIK3CA gene was found in generation of p110 alpha (p110α) protein through an instruction process. p110 alpha acts as a catalytic subunit of phosphatidylinositol 3-kinase (PI3K) proceed phosphorylation of signal molecules through PI3K pathway. This PI3K involved in regulation of cellular growth, transformation, adhesion, apoptosis, survival and motility. In some situations the PI3K/Akt pathway get altered due to mutation in PIK3CA gene produced oncogenic event in human malignancy. Methods: The goal of this work is to describe the PI3K signaling pathway including mutational activation of PIK3CA gene and inhibitors have been developed or under clinical trials for the targeting of PI3K or PI3KR kinases. Results: Various inhibitors such as Morpholine, pyrimidines, benzenesulfonamide, pyridopyrimidinone, imidazo[1,5]naphthyridine, benzeneacylhydrazones, thienopyrimidine, aminopyridopyrimidine, imidazopyridine, imidazo[1,2-a]pyridine, thiazolopyrimidinone, quinolines and quinoxalines, thieno[3,2-b]pyran-7-one, morpholino-1,3-benzoxazines, quinalozinones, pyrido [3,2-d]pyrimidines, benzo[d]thiazol-2-yl)acetamide, aminopyrimidines, chalcone, azaindole, pyrazolopyrimidine and pyridine, thienobenzoxepin, phenylquinazolines, pyrazolo[1,5-a]pyridines, imidazolo-pyrimidine etc. were investigated under laboratory level as PI3K inhibitors in which few having PI3K and mTOR dual inhibitory activities. Conclusion: After a long term of prognostic standpoint, PIK3CA mutations discussed as a major target for various cancers. These PIK3CA mutations were found in various exon including 1,2,4,6,7,9,13,18 and 20 which may be a cause of different cancers such as breast, colon, ovarian, gastric, brain, lung etc. In clinical trials these mutations still remain question marks for presence or absence to the scientist regarding future perspective. The opinion of these studies is to development of more specific inhibitors of PI3K pathway which produce tremendous impact on various cancers developed due to PIK3CA mutations. © 2016 Bentham Science Publishers.

Iveson T.,University of Southampton | Donehower R.C.,Johns Hopkins Cancer Center | Davidenko I.,State Institution of Public Health Regional Clinical Oncology Dispensary | Tjulandin S.,Russian Cancer Research Center | And 12 more authors.
The Lancet Oncology | Year: 2014

Background: Dysregulation of the hepatocyte growth factor (HGF)/MET pathway promotes tumour growth and metastasis. Rilotumumab is a fully human, monoclonal antibody that neutralises HGF. We aimed to assess the safety, efficacy, biomarkers, and pharmacokinetics of rilotumumab combined with epirubicin, cisplatin, and capecitabine (ECX) in patients with advanced gastric or oesophagogastric junction cancer. Methods: We recruited patients (≥18 years old) with unresectable locally advanced or metastatic gastric or oesophagogastric junction adenocarcinoma, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, who had not received previous systemic therapy, from 43 sites worldwide. Phase 1b was an open-label, dose de-escalation study to identify a safe dose of rilotumumab (initial dose 15 mg/kg intravenously on day 1) plus ECX (epirubicin 50 mg/m2 intravenously on day 1, cisplatin 60 mg/m2 intravenously on day 1, capecitabine 625 mg/m2 twice a day orally on days 1-21, respectively), administered every 3 weeks. The phase 1b primary endpoint was the incidence of dose-limiting toxicities in all phase 1b patients who received at least one dose of rilotumumab and completed the dose-limiting toxicity assessment window (first cycle of therapy). Phase 2 was a double-blind study that randomly assigned patients (1:1:1) using an interactive voice response system to receive rilotumumab 15 mg/kg, rilotumumab 7·5 mg/kg, or placebo, plus ECX (doses as above), stratified by ECOG performance status and disease extent. The phase 2 primary endpoint was progression-free survival (PFS), analysed by intention to treat. The study is registered with, number NCT00719550. Findings: Seven of the nine patients enrolled in the phase 1b study received at least one dose of rilotumumab 15 mg/kg, only two of whom had three dose-limiting toxicities: palmar-plantar erythrodysesthesia, cerebral ischaemia, and deep-vein thrombosis. In phase 2, 121 patients were randomly assigned (40 to rilotumumab 15 mg/kg; 42 to rilotumumab 7·5 mg/kg; 39 to placebo). Median PFS was 5·1 months (95% CI 2·9-7·0) in the rilotumumab 15 mg/kg group, 6·8 months (4·5-7·5) in the rilotumumab 7·5 mg/kg group, 5·7 months (4·5-7·0) in both rilotumumab groups combined, and 4·2 months (2·9-4·9) in the placebo group. The hazard ratio for PFS events compared with placebo was 0·69 (80% CI 0·49-0·97; p=0·164) for rilotumumab 15 mg/kg, 0·53 (80% CI 0·38-0·73; p=0·009) for rilotumumab 7·5 mg/kg, and 0·60 (80% CI 0·45-0·79; p=0·016) for combined rilotumumab. Any grade adverse events more common in the combined rilotumumab group than in the placebo group included haematological adverse events (neutropenia in 44 [54%] of 81 patients vs 13 [33%] of 39 patients; anaemia in 32 [40%] vs 11 [28%]; and thrombocytopenia in nine [11%] vs none), peripheral oedema (22 [27%] vs three [8%]), and venous thromboembolism (16 [20%] vs five [13%]). Grade 3-4 adverse events more common with rilotumumab included neutropenia (36 [44%] vs 11 [28%]) and venous thromboembolism (16 [20%] vs four [10%]). Serious adverse events were balanced between groups except for anaemia, which occurred more frequently in the combined rilotumumab group (ten [12%] vs none). Interpretation: Rilotumumab plus ECX had no unexpected safety signals and showed greater activity than placebo plus ECX. A phase 3 study of the combination in MET-positive gastric and oesophagogastric junction cancer is in progress. © 2014 Elsevier Ltd.

Kumar R.V.,Kidwai Memorial Institute of Oncology | Bhasker S.,All India Institute of Medical Sciences
Journal of Cancer Policy | Year: 2014

Cervical cancer is the commonest malignancy among women in resource-poor low- and middle-income countries (LMICs). Western models of health-care organization and delivery may not be suitable for these settings. Research in health services needs to be undertaken before Western oncological prevention and management protocols can be adopted from the innovative affluent countries. It is possible to tailor cervical cancer prevention and management protocols and to avoid inappropriate technology on the basis of a literature review of demographic and clinical profiles in LMICs. © 2013 The Authors.

Saminathan S.,Kidwai Memorial Institute of Oncology
Journal of applied clinical medical physics / American College of Medical Physics | Year: 2010

Intensity-modulated radiotherapy treatment demands stringent quality assurance and accurate dose determination for delivery of highly conformal dose to the patients. Generally 3D dose distributions obtained from a treatment planning system have to be verified by dosimetric methods. Mainly, a comparison of two-dimensional calculated and measured data in several coplanar planes is performed. In principle, there are many possibilities to measure two-dimensional dose distributions such as films, flat-panel electronic portal imaging devices (EPID), ion chambers and ionization chamber arrays, and radiographic and radiochromic films. The flat-panel EPIDs show a good resolution and offer a possibility for real-time measurements: however to convert the signal into dose, a separate commercial algorithm is required. The 2D ion chamber array system offers the real-time measurements. In this study, dosimetric characteristics of 2D ion chamber array matrix were analyzed for verification of radiotherapy treatments. The dose linearity and dose rate effect of the I'matriXX device was studied using 6 MV, 18 MV photons and 12 MeV electrons. The output factor was estimated using I'matriXX device and compared with ion chamber measurements. The ion chamber array system was found to be linear in the dose range of 2-500 cGy and the response of the detector was found to be independent of dose rate between 100 MU/min to 600 MU/min. The estimated relative output factor with I'matriXX was found to match very well with the ion chamber measurements. To check the final dose delivered during IMRT planning, dose distribution patterns such as field-in-field, pyramidal, and chair tests were generated with the treatment planning system (TPS) and the same was executed in the accelerator and measured with the I'matriXX device. The dose distribution pattern measured by the matrix device for field-in-field, pyramidal, and chair test were found to be in good agreement with the calculated dose distribution by TPS both for 6 and 18 MV photons (gamma < or = 1: 96%, criteria 3%, 3 mm). Two 7-field IMRT plans (one prostate, one head and neck) dose distribution patterns were also measured with I'matriXX device and compared with film dosimetry. The measurements and evaluation proves that I'matriXX can be used for quantifying absolute dose. Moreover, using I'matriXX as absolute dosimeter in IMRT field verification, avoids the time-consuming procedure of making ionometric measurement for absolute dose estimation and film for dose distribution verification. The I'matriXX can also used for routine quality assurance checks like flatness, symmetry, field width, and penumbra of the linear accelerator beam.

Burrah R.,Kidwai Memorial Institute of Oncology
The Indian journal of chest diseases & allied sciences | Year: 2012

Solitary fibrous tumour of the pleura is a rare primary pleural neoplasm. These tumours are usually asymptomatic and are incidentally detected. Majority of these neoplasms are benign and surgical excision provides excellent results. With the widespread use of imaging and better diagnostic criteria, this tumour is likely to be detected more frequently. We encountered a patient with a giant solitary fibrous tumour of the pleura. In this report, we describe the case of a patient with a giant solitary fibrous tumour of the pleura, review the literature and present the details of management of this patient.

Shwetha B.,Kidwai Memorial Institute of Oncology
Journal of applied clinical medical physics / American College of Medical Physics | Year: 2010

HDR brachytherapy treatment planning often involves optimization methods to calculate the dwell times and dwell positions of the radioactive source along specified afterloading catheters. The purpose of this study is to compare the dose distribution obtained with geometric optimization (GO) and volume optimization (VO) combined with isodose reshaping. This is a retrospective study of 10 cervix HDR interstitial brachytherapy implants planned using geometric optimization and treated with a dose of 6 Gy per fraction. Four treatment optimization plans were compared: geometric optimization (GO), volume optimization (VO), geometric optimization followed by isodose reshape (GO_IsoR), and volume optimization followed by isodose reshape (VO_IsoR). Dose volume histogram (DVH) was analyzed and the four plans were evaluated based on the dosimetric parameters: target coverage (V100), conformal index (COIN), homogeneity index (HI), dose nonuniformity ratio (DNR) and natural dose ratio (NDR). Good target coverage by the prescription dose was achieved with GO_ IsoR (mean V100 of 88.11%), with 150% and 200% of the target volume receiving 32.0% and 10.4% of prescription dose, respectively. Slightly lower target coverage was achieved with VO_IsoR plans (mean V100 of 86.11%) with a significant reduction in the tumor volume receiving high dose (mean V150 of 28.29% and mean V200 of 7.3%). Conformity and homogeneity were good with VO_ IsoR (mean COIN = 0.75 and mean HI = 0.58) as compared to the other optimization techniques. VO_IsoR plans are superior in sparing the normal structures while also providing better conformity and homogeneity to the target. Clinically acceptable plans can be obtained by isodose reshaping provided the isodose lines are dragged carefully.

Suma T.L.,Kidwai Memorial Institute of Oncology
Journal of Pediatric Hematology/Oncology | Year: 2016

Tumors arising from urachus in children are exceedingly rare and sporadically reported in literature. Being a midline structure, the urachus may harbor neoplastic germ cell elements and can occasionally present as a case of acute abdomen. A 20-month-old toddler presented with spontaneous rupture of an urachal yolk sac tumor causing hemoperitoneum. He underwent resection, received platinum-based chemotherapy and presently remains well on follow-up. Despite its rarity, urachal germ cell tumors must be considered in a child with acute abdomen and tumor markers must be measured preemptively in such cases. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

Rao V.,Kidwai Memorial Institute of Oncology
Indian journal of cancer | Year: 2010

Tobacco is a well-acknowledged social and health evil. The history of tobacco use traces back to the dawn of human civilization and has been deeply entrenched into the human society since time immemorial. The social, economic, and health impact of tobacco has been a subject of intense debate over the recent decades. For India, this problem has been a unique one, with the consumption patterns either largely influenced by the socioeconomic backgrounds or dictated by the cultural diversity. With more than 200 million tobacco consumers in the country at present, it becomes imperative to address this health hazard and stir up strong measures toward damage control. This article addresses the tobacco problem, its evolution, and the factors that have affected the growth of Indian tobacco industry. It also highlights the current legislative measures against tobacco, fiscal gains to the government, and the serious health and economic impact to the consumer, compounded by the increasing cost of private health care in the present era of consumerism.

Lakshmaiah K.C.,Kidwai Memorial Institute of Oncology | Jacob L.A.,Kidwai Memorial Institute of Oncology | Aparna S.,Kidwai Memorial Institute of Oncology | Lokanatha D.,Kidwai Memorial Institute of Oncology | Saldanha S.C.,Kidwai Memorial Institute of Oncology
Journal of Cancer Research and Therapeutics | Year: 2014

Epigenetics is the study of heritable alterations in gene expression that are not accompanied by the corresponding change in DNA sequence. Three interlinked epigenetic processes regulate gene expression at the level of chromatin, namely DNA methylation, nucleosomal remodeling and histone covalent modifications. Post-translational modifications that occur on certain amino acid residues of the tails of histone proteins modify chromatin structure and form the basis for "histone code". The enzymes Histone Acetyl Transferase (HAT) and Histone Deacetylase (HDAC) control the level of acetylation of histones and thereby alter gene expression. In many cancers, the balance between HAT and HDAC is altered. HDAC enzymes are grouped into four different classes namely Class I (HDAC1, HDAC2, HDAC3, and HDAC8), Class II (HDAC4, HDAC5, HDAC6, HDAC7, HDAC9, and HDAC10), Class III HDAC and Class IV (HDAC11). Histone Deacetylase Inhibitors (HDACI) exert anticancer activity by promoting acetylation of histones as well as by promoting acetylation of non-histone protein substrates. The effects of HDACI on gene transcription are complex. They cause cell cycle arrest, inhibit DNA repair, induce apoptosis and acetylate non histone proteins causing downstream alterations in gene expression. HDACI are a diverse group of compounds, which vary in structure, biological activity, and specificity. In general, HDACIs contain a zinc-binding domain, a capping group, and a straight chain linker connecting the two. They are classified into four classes namely short chain fatty acids, hydroxamic acids, cyclic peptides and synthetic benzamides. This review describes the clinical utility of HDACI as monotherapy as well as combination therapy with other treatment modalities such as chemotherapy and radiotherapy. Adverse effects and shortcomings of treatment with HDACI are also discussed in detail.

Devi P.S.,Kidwai Memorial Institute of Oncology
Indian Journal of Palliative Care | Year: 2011

In the trajectory of disease progress and treatment plan, patients and the family members are confronted with challenging situations like unsurmountable physical distress, inadequate coping patterns,unanswered spiritual issues in the background of serious threat to very existence of life leads to a debilitating Quality of life.The Palliative Care team approach addresses all the issues and also sees the patient to go through the protocols of Palliative care management as well as Oncological treatment plan. Further, this fecilitates a smooth transition from the hospital to home and hospice care. Various studies conducted globally revealed that patients received palliative care intervention along with oncological treatments had higher scores of Quality of life compared to patients received onlyoncology care alone.This article discusses the various factors contributing to late referrals to palliative care team and also care giver′s views pertaining to need for early referral. Timely referral to palliative care minimises the patient′s and care giver′s distress,ensures modest Quality of life and appropriate measures at the end of life care.

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