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ABSTRACT: Background: Lung cancer is one of the commonest and most lethal cancers throughout the world. The epidemiological and pathological profile varies among different ethnicities and geographical regions. At present adenocarcinoma is the commonest histological subtype of non-small cell lung cancer (NSCLC) in most of the Western and Asian countries. However, in India squamous cell carcinoma has been reported as the commonest histological type in most of the series. The aim of the study was to analyze the current clinico-pathological profile and survival of lung cancer at our centre. Materials and Methods: We analyzed 434 pathologically confirmed lung cancer cases registered at our centre over a period of three years. They were evaluated for their clinical and pathological profiles, treatment received and outcome. The available histology slides were reviewed by an independent reviewer. Results: Median age was 55 years with a male:female ratio of 4.6:1. Some 68% of patients were smokers. There were 85.3% NSCLC and 14.7% SCLC cases. Among NSCLCs, adenocarcinoma was the commonest histological subtype after the pathology review. Among NSCLC, 56.8% cases were of stage IV while among SCLC 71.8% cases had extensive stage disease. Some 29% of patients could not receive any anticancer treatment. The median overall and progression free survivals of the patients who received treatment were 12.8 and 7.8 months for NSCLC and 9.1 and 6.8 months for SCLC. Conclusions: This analysis suggests that adenocarcinoma may now be the commonest histological subtype also in India, provided a careful pathological review is done. Most of the patients present at advanced stage and outcome remains poor.
Asian Pacific journal of cancer prevention: APJCP 01/2013; 14(1):489-494. · 0.66 Impact Factor
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ABSTRACT: Single nucleotide polymorphisms (SNPs) of the CTLA-4 gene have been implicated in susceptibility to different cancer in different ethnic populations. We assessed the association of five SNPs [-1722C/T, -1661A/G and -318C/T in the promoter region49A/G in exon 1 and CT60A/G in the 3'untranslated region (UTR)] with tobacco-related oral squamous cell carcinoma (OSCC) in North Indian subjects. We genotyped 130 OSCC patients and 180 normal subjects by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) using BbvI, MseI, NcoI and BstEII restriction endonucleases. Among these SNPs, -1722CC, -1661AG and CT60AA genotypes were more prevalent in OSCC patients as compared to controls and in the logistic regression analysis with odd ratio (OR) 2.85, 95% CI (0.69-11.68); OR 2.48, 95% CI (1.29-4.78) and OR 3.0, 95% CI (1.43-6.28) respectively, these genotypes showed strong association with OSCC risk. With higher prevalence in controls 49GG genotype and G allele (OR 0.57, 95% CI 0.40-0.81) appeared to be protective. Moreover, TACAG, TACGA and TATAG appeared as susceptible while TACGG and CACGG appeared as protective haplotypes. These results suggest significant risk modifying effects of CTLA-4 -1722C/T, -1661A/G, -318T/C, CT60 A/G and 49A/G SNPs in tobacco-related OSCC in North Indian population.
Human immunology 12/2012; · 2.55 Impact Factor
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Kamaldeep Gill,
Abhay K Singh,
Vaishali Kapoor,
Lokesh Nigam,
Rahul Kumar,
Prasida Holla,
Satya N Das,
Savita Yadav,
Naidu Subbarao, Bidhu Kalyan Mohanti,
Sharmistha Dey
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ABSTRACT: BACKGROUND: The p38α MAP kinase pathway is involved in inflammation, cell differentiation, growth, apoptosis and production of pro-inflammatory cytokines TNF-α and IL-1β. The overproduction of these cytokines plays an important role in cancer. The aim of this work was to design a peptide inhibitor on the basis of structural information of the active site of p38α. METHODS: A tetrapeptide, VWCS as p38α inhibitor was designed on the basis of structural information of the ATP binding site by molecular modeling. The inhibition study of peptide with p38α was performed by ELISA, binding study by Surface Plasmon Resonance and anti-proliferative assays by MTT and flow cytometry. RESULTS: The percentage inhibition of designed VWCS against pure p38α protein and serum of HNSCC patients was 70.30 and 71.5%, respectively. The biochemical assay demonstrated the K(D) and IC(50) of the selective peptide as 7.22 x 10(-9)M and 20.08 nM, respectively. The VWCS as inhibitor significantly reduced viability of oral cancer KB cell line with an IC(50) value of 10μM and induced apoptosis by activating Caspase 3 and 7. CONCLUSIONS: VWCS efficiently interacted at the ATP binding pocket of p38α with high potency and can be used as a potent inhibitor in case of HNSCC. GENERAL SIGNIFICANCE: VWCS can act as an anticancer agent as it potentially inhibits the cell growth and induces apoptosis in oral cancer cell-line in a dose as well as time dependent manner. Hence, p38α MAP kinase inhibitor can be a potential therapeutic agent for human oral cancer.
Biochimica et Biophysica Acta 12/2012; · 4.66 Impact Factor
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ABSTRACT: Autophagy is a physiologically regulated and evolutionary conserved process that plays a critical role in degradation of cytoplasmic proteins and other macromolecules within the lysosomes. Beclin-1, the mammalian orthologue of yeast Atg6, is an important mediator of autophagy that has been studied in many human cancers. However, the expression of Beclin-1 has not yet been investigated in oral cancer. We for the first time investigated the expression of Beclin-1 in serum and tissues and correlated it with the clinic-pathological features of oral cancer patients. m-RNA expression of Beclin-1 was evaluated in tumor and normal areas of surgical specimens from 10 oral cancer patients by real-time PCR. Approximately, 8-fold lower expression (p<0.001) of Beclin-1 mRNA was observed in tumor tissue as compared to the normal tissue. Serum levels of Beclin-1 were evaluated by SPR and ELISA. No significant difference was observed in serum Beclin-1 levels in patients as compared to healthy subjects, similarly no correlation was found between serum levels and clinic-pathological parameters such as stage, lymph node involvement and tumor size. Our results demonstrate that down-regulation of Beclin-1 may play an important role in the development and progression of oral cancer possibly by dysregulation of autophagy in tumor cells.
Biochemical and Biophysical Research Communications 05/2012; 422(4):764-9. · 2.48 Impact Factor
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ABSTRACT: A majority of patients with esophageal cancer present with inoperable disease and require rapid and long-lasting palliation of dysphagia.
To compare the duration of relief of dysphagia in patients with inoperable esophageal cancer treated with esophageal stenting alone or a combination of esophageal stenting and external beam radiotherapy (EBRT), and to assess overall survival, treatment-related complications, and quality of life (QOL) in the two groups.
Patients with inoperable esophageal cancer and with high grade dysphagia were randomized to receive esophageal stenting with self-expandable metal stent (Ultraflex) alone (Group I), versus a combination of stenting followed by EBRT (30 gray in ten divided fractions over 2 weeks) (Group II). Dysphagia relief, overall survival, QOL (using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30, version 3), and treatment-related complications were assessed in the two groups.
From April 2007 to March 2009, 84 patients were randomized to receive esophageal stent alone (42 patients) or a combination of stent and EBRT (42 patients). The two groups were comparable in demographics, tumor characteristics, indications for palliative treatment, and pretreatment dysphagia score. Dysphagia scores improved significantly in both groups following stent insertion. However, dysphagia relief was more sustained in Group II than in Group I (7 vs. 3 months, p = 0.002). Overall median survival was significantly higher in Group II than in Group I (180 vs. 120 days, p = 0.009). Addition of radiotherapy following stenting prolonged the mean dysphagia-free survival (118.6 ± 55.8 vs. 96.8 ± 43.0 days, p = 0.054). There was significant improvement in all QOL parameters at 1 week after stenting. The QOL, however, significantly declined immediately after radiotherapy. There was no treatment-related mortality, and the incidence of complications was similar in the two groups.
Post-stenting EBRT effectively prolongs duration of dysphagia relief and improves overall survival in inoperable esophageal cancer.
Journal of Gastrointestinal Cancer 03/2012; 43(1):63-9.
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ABSTRACT: Translation of early findings from basic research is aimed to benefit cancer therapeutics. We report the p38α level in serum of head and neck squamous cell carcinoma (HNSCC) patients indicating it as a prognostic marker and established its correlation with radiation therapy (RT).
The case-controlled study was performed on 120 HNSCC patients from whom 81 patients and 45 controls were statistically analyzed. The p38α estimation was done at pre-RT, during-RT and post-RT using a real time Surface Plasmon Resonance (SPR) technology, ELISA and western blot.
HNSCC patients showed threefold increase in p38α level when compared to control (p value<0.0001). The estimated concentration of p38α in a temporal manner, before-RT, during-RT and post-RT was 0.61 ng/μl (95%CI: 0.53-0.69), 0.35 ng/μl (95%CI: 0.31-0.38) and 0.30 ng/μl (95%CI: 0.26-0.33), respectively. Among the 81 cases, 70 patients (86.42%) showed a declined p38α in response to RT as evaluated by SPR and were responding clinically (clinical tumor regression).
This study showed elevated p38α level at cancer diagnosis and a statistically significant decline during-RT and post-RT periods. Hence, it can emerge as a prognostic marker supporting the candidature of p38α as a suitable serum marker in HNSCC.
Clinica chimica acta; international journal of clinical chemistry 01/2012; 413(1-2):219-25. · 2.54 Impact Factor
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ABSTRACT: Primary osteosarcoma of skull base is extremely rare. We present a case of primary osteosarcoma arising in greater wing of sphenoid in a child. Our patient had an incomplete excision after which he received adjuvant chemotherapy and radiotherapy. There was good response to adjuvant chemoradiotherapy and the patient is disease free at a follow-up of 18 months. Treatment of skull base osteosarcomas is difficult, as complete excision is often not possible. To the best of our knowledge, this is the first case of sphenoid wing osteosarcoma in childhood to be reported in literature.
Journal of Pediatric Hematology/Oncology 12/2011; 34(2):e59-62. · 1.16 Impact Factor
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ABSTRACT: Transforming growth factor (TGF)-β1, the most abundant isoform of TGF-β have been implicated in various stages of carcinogenesis such as epithelial to mesenchymal transition, enhanced expression of metalloproteases, down-regulation of cellular adhesion molecule, increased tumor motility and angiogenesis as well as local and systemic immunosuppression leading to a more aggressive and metastatic behavior. We assessed the association of TGF-β1 functional genetic polymorphisms at codon 10 (869 T>C) and 25 (915 G>C) of exon 1 in 140 patients with tobacco-related oral squamous cell carcinoma (OSCC) and 120 normal subjects by PCR-RFLP. The frequency of 869 CC genotype and C allele were significantly higher in patients as compared to controls (P(c), 0.024 and 0.0004, respectively) while no significant difference was observed in the frequency of 915 CC genotype and C allele. In logistic regression analysis CC genotype (OR, 3.87; 95% CI, 1.78-8.41) and C allele (OR, 2.20; 95% CI 1.51-3.20) appeared as susceptible while TT genotype and T allele as protective. In addition C(869)-C(915) haplotype with OR of 2.48 at 95% CI, 1.51-4.06 significantly (P=0.0003) increased the risk of tobacco-related OSCC in Asian Indians.
Oral Oncology 08/2011; 47(12):1117-21. · 2.86 Impact Factor
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ABSTRACT: Oral mucositis is a frequent and serious complication in patients receiving chemo-radiotherapy for head and neck squamous cell carcinoma. This study evaluated the effects of administering Lactobacillus brevis CD2 lozenges on the incidence and severity of mucositis and tolerance to chemo-radiotherapy.
Two hundred patients suitable for chemo-radiotherapy were enrolled in a randomised, double-blind study to receive daily treatment with lozenges containing either L. brevis CD2 or placebo. Anticancer therapy was RT 70 Grays/35 fractions over 7 weeks with weekly Inj. Cisplatin 40 mg/m(2). The study treatment was given during, and for 1 week after completion of anticancer therapy. Primary end-points were the incidence of grade III and IV oral mucositis and the percentage of patients able to complete anticancer treatment.
The efficacy analysis included the 188 patients who received ≥ 1 week of study treatment. Grade III and IV mucositis developed in 52% of patients in the L. brevis CD2 arm and 77% in the placebo arm (P<0.001). Anticancer treatment completion rates were 92% in the L. brevis CD2 arm and 70% in the placebo arm (P=0.001). A larger proportion of patients remained free of mucositis when treated with L. brevis CD2 (28%) compared to the placebo (7%).
L. brevis CD2 lozenges reduced the incidence of grade III and IV anticancer therapy-induced oral mucositis and were associated with a lower overall rate of mucositis and a higher rate of anticancer treatment completion.
European journal of cancer (Oxford, England: 1990) 07/2011; 48(6):875-81. · 4.12 Impact Factor
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Journal of cancer research and therapeutics 07/2011; 7(3):357-8. · 0.83 Impact Factor
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ABSTRACT: The over expression of LL37, an antimicrobial peptide belonging~to the cathelicidin family has implication in the progression of human malignancy but the exact role is still not clear. This study aims to elucidate the correlation of LL37 with Head and Neck Squamous Cell Carcinoma (HNSCC) and the consequences of radiotherapy on it. The LL37 levels were quantified in serum samples of control and HNSCC patients at pre-RT, during-RT and post-RT using a real time Surface Plasmon Resonance technology and ELISA. The LL37 of 50 HNSCC patients was significantly (p < 0.0001) threefold higher than the 25 controls and declined with respect to radiation therapy (p < 0.0001) supporting its candidature as a prognostic marker in HNSCC.
Cancer biomarkers: section A of Disease markers 01/2011; 10(3-4):125-34. · 1.08 Impact Factor
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Atul Sharma,
Amit Dutt Dwary, Bidhu Kalyan Mohanti,
Surya V Deo,
Sujoy Pal,
Vishnu Sreenivas,
Vinod Raina,
Nootan Kumar Shukla,
Sanjay Thulkar,
Pramod Garg,
Surendra Pal Chaudhary
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ABSTRACT: We designed this study to evaluate efficacy of modified gemcitabine and oxaliplatin (mGEMOX) over best supportive care (BSC) or fluorouracil (FU) and folinic acid (FA) in unresectable gall bladder cancer (GBC).
Patients with unresectable GBC were enrolled for single center randomized study. Arm A, BSC; arm B, FU 425 mg/m(2) and FA 20 mg/m(2) intravenous (IV) bolus weekly for 30 weeks (FUFA); arm C, gemcitabine 900 mg/m(2) and oxaliplatin 80 mg/m(2) IV infusion on days 1 and 8 every 3 weeks for maximum of six cycles. Eighty-one patients were randomly assigned, arms A (n = 27), B (n = 28), and C (n = 26).
Complete response plus partial response in the three groups was 0 (0%), four (14.3%), and eight (30.8%) respectively (P < .001). Two patients in the mGEMOX arm and one patient in the FUFA arm underwent curative resection after chemotherapy. One patient in the mGEMOX arm had complete pathologic response. Median overall survival (OS) was 4.5, 4.6, and 9.5 months for the BSC, FUFA, and mGEMOX arms (P = .039), respectively. Progression-free survival (PFS) was 2.8, 3.5, and 8.5 months for the three groups (P < .001). There was no difference in grade 3/4 toxicities in the chemotherapy arms except transaminitis, which was more prevalent in mGEMOX arm (P = .04). Two patients in the FUFA arm and 10 patients in the mGEMOX arm had grade 3 or 4 myelosuppression. Two patients in the mGEMOX group had neutropenic fever that resolved with antibiotics.
This randomized controlled trial confirmed the efficacy of chemotherapy (mGEMOX) compared with BSC and FUFA in improving OS and PFS in unresectable GBC.
Journal of Clinical Oncology 10/2010; 28(30):4581-6. · 18.37 Impact Factor
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ABSTRACT: We assessed the association of COX-2 polymorphisms at promoter sites -1195, -765 and at 3'UTR (8473) in 193 patients with oral squamous cell carcinoma (OSCC) and 137 normal subjects by PCR-RFLP. Although no significant difference was observed in the frequency of COX-2 -1195G>A, -765G>C and 8473C>T single nucleotide polymorphisms (SNPs) between patients and controls, COX-2 -1195G/A genotype showed higher while -765G/C and 8473C/T showed lower prevalence in patients as compared to normal subjects. Logistic regression analysis of these three polymorphisms revealed a quantitative risk associated with -1195G>A SNP (OR 3.07 at 95%CI) while -765G>C and 8473C>T appeared to be protective. Results of the present study indicate that these three functional variants in the COX-2 regulatory region may contribute to risk modification of tobacco-related oral squamous cell carcinoma in Asian Indians.
Oral Oncology 08/2010; 46(8):622-6. · 2.86 Impact Factor
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ABSTRACT: Nonmetastatic extraocular retinoblastoma is a common entity in South-East Asia. We did a retrospective study of patients treated for isolated extraocular retinoblastoma, that is, International retinoblastoma staging system stages II and III, using a uniform chemotherapy protocol at our oncology center, between June 2003 and June 2008. Out of the 25 patients having nonmetastatic extraocular retinoblastoma, 6 were in stage II, and 19 in stage III. The probability of event-free survival was 0.54 at 18 months of follow-up with no significant difference between the 2 stages and the presence of optic nerve involvement; 11 out of 13 relapses were systemic. This is the largest case series of nonmetastatic extraocular retinoblastoma from South-East Asia.
Journal of Pediatric Hematology/Oncology 02/2010; 32(2):e42-5. · 1.16 Impact Factor
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ABSTRACT: Radiotherapy (RT) is an important treatment modality in head and neck cancers. Loss of weight during RT due to various factors is a matter of concern. This study was conducted to see the pattern of weight loss and the causative factors involved. One hundred forty patients with head and neck cancer treated with radical RT, concurrent chemoradiation, or postoperative RT were retrospectively studied. A dose of 70 Gy was given in the radical and in the chemoradiation schedule. In postoperative RT, a dose of 60-64 Gy was delivered. During the weekly review of the patients, serial recording of their weight was done along with measurement of other parameters. Analysis was done to see which factors were causative in patients having a weight loss of >5 kg and of >10%. Three variables were found to be significant for the >5-kg weight loss. These were a low initial Karnofsky performance score (KPS; P < 0.001), use of chemoradiation (P < 0.001), and a total dose of >60 Gy (P = 0.04). For the >10% weight loss, the significant factors were low initial KPS (P < 0.001) and use of chemoradiation (P < 0.001). Therefore, it is important to take care of the nutrition of those patients who have a low KPS, are on chemoradiation, or will be delivered a dose of >60 Gy. The role of prophylactic Ryle's tube placement or agents such as megestrol acetate in such patients should be further investigated.
Nutrition and Cancer 02/2003; 47(2):136-40. · 2.78 Impact Factor
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ABSTRACT: Data on the clinical profile of early breast cancer (EBC) from India is scant. Due to differences in genetics, environment, lifestyle, socio-demographic structure and ethnicity, the presentation and behavior of breast cancer in India may be different.
To analyze the clinical presentation and outcome of EBC patients.
A single center retrospective study.
Data from 487 EBC patients registered and treated at our institute from 1993 through 1999 were analyzed. Cox's multivariate regression test was used to determine prognostic factors for overall and disease-free survival (OS & DFS).
The median age was 47 years and 49.7% patients were pre-menopausal. Ninety-six per cent patients presented with a lump. Stages I, IIa, and IIb comprised 7.8%, 38.8%, and 47.6% respectively. Only 11.3% patients opted for breast-conserving surgery (BCS) while the remaining 88.7% underwent modified radical mastectomy (MRM). Adjuvant chemotherapy was administered to 275 (56.5%), and radiotherapy to 146 (29.9%). Estrogen receptor status was known in 173, of whom 93 (53.7%) were positive. Most patients were prescribed Tamoxifen for 5 years. At a median follow-up of 48 months, 126 (25.9%) patients had relapsed (systemic 107, loco-regional 19) and 94 (19.3%) had died. Five-year DFS and OS were 73% and 78%, respectively. On multivariate analysis, four positive nodes adversely influenced survival (P< 0.01).
The median age at presentation was 47 years, significantly lower than most Western figures. The majority (86.4%) had a lump size > two cm. BCS was done in only 11% and the rest underwent MRM. Nodal involvement was the significant prognostic factor.
Indian Journal of Cancer 42(1):40-5.
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ABSTRACT: A study of eight cases of head and neck cancers, to see if the cord was getting a higher dose in the antero-posterior (A-P) fields, compared to the bilateral (B/L) fields.
Radiation damage to the spinal cord is a critical issue for the radiation oncologists. This study was conducted to evaluate, if the dose to the spinal cord is higher by the antero-posterior (A-P) fields, compared to the bilateral (B/L) fields.
Eight cases of head and neck cancer were taken in our study. Two beam arrangements were placed in the treatment planning system, the B/L and the A-P fields. The DVH's for the cord dose were recorded and compared in both plans, with a standard fraction size of 200 cGy/fraction.
The mean dose to the spinal cord was 168.06 cGy in A-P arrangement, while it was 133.75 cGy in the B/L arrangement.
A-P field arrangement in head and neck malignancies delivers a higher dose to the spinal cord. Therefore, we need to spare the cord at an earlier dose limit.
Journal of cancer research and therapeutics 2(2):65-7. · 0.83 Impact Factor
