Morinda citrifolia, also known as Great Morinda, Indian Mulberry, or Noni, is a plant belonging to the family Rubiaceae. A number of major chemical compounds have been identified in the leaves, roots, and fruits of the Noni plant. The fruit juice is in high demand in alternative medicine for different kinds for illnesses such as arthritis, diabetes, high blood pressure, muscle ached and pains, menstrual difficulties, headache, heart diseases, AIDS, gastric ulcer, sprains, mental depression, senility, poor digestion, arteriosclerosis, blood vessel problems, and drug addiction. Several studies have also demonstrated anti-inflammatory, antioxidant and apoptosis-inducing effects of Noni in various cancers. Based on a toxicological assessment, Noni juice was considered as safe. Though a large number of in vitro, and, to a certain extent, in vivo studies demonstrated a range of potentially beneficial effects, clinical data are essentially lacking. To what extent the findings from experimental pharmacological studies are of potential clinical relevance is not clear at present and this question needs to be explored in detail before an recommendations can be made.
Indian spices are well known for their numerous health benefits, flavour, taste, and colour. Recent Advancements in chemical technology have led to better extraction and identification of bioactive molecules (phytochemicals) from spices. The therapeutic effects of spices against diabetes, cardiac problems, and various cancers has been well established. The present in silico study aims to investigate the binding affinity of 29 phytochemicals from 11 Indian spices with two prominent proteins, BCL3 and CXCL10 involved in invasiveness and bone metastasis of breast cancer. The three-dimensional structures of 29 phytochemicals were extracted from PubChem database. Protein Data Bank was used to retrieve the 3D structures of BCL3 and CXCL10 proteins. The drug-likeness and other properties of compounds were analysed by ADME and Lipinski rule of five (RO5). All computational simulations were carried out using Autodock 4.0 on Windows platform. The proteins were set to be rigid and compounds were kept free to rotate. In-silico study demonstrated a strong complex formation (positive binding constants and negative binding energy ΔG) between all phytochemicals and target proteins. However, piperine and sesamolin demonstrated high binding constants with BCL3 (50.681 × 103 mol-1, 137.76 × 103 mol-1) and CXCL10 (98.71 × 103 mol-1, 861.7 × 103 mol-1), respectively. The potential of these two phytochemicals as a drug candidate was highlighted by their binding energy of -6.5 kcal mol-1, -7.1 kcal mol-1 with BCL3 and -6.9 kcal mol-1, -8.2 kcal mol-1 with CXCL10, respectively coupled with their favourable drug likeliness and pharmacokinetics properties. These findings underscore the potential of piperine and sesamolin as drug candidates for inhibiting invasiveness and regulating breast cancer metastasis. However, further validation through in vitro and in vivo studies is necessary to confirm the in silico results and evaluate their clinical potential.
Lasrado, Savita;Moras, Kuldeep;Pinto, George Jawahar Oliver;Bhat, Mahesh;Hegde, Sanath;Sathian, Brijesh;Luis, Neil Aaron
Asian Pacific Journal of Cancer Prevention
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v.15
no.10
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pp.4147-4152
/
2014
Standard therapy for advanced head and neck cancer consists of a combination of surgery and radiation. However, survival of this patient population has not improved during the past 20 years. Many different multimodality treatment schedules have been proposed, and chemotherapy is often used with the intent of organ preservation. The present study was intended to establish the efficacy of concomitant chemoradiation with a single agent carboplatin in advanced head and neck cancers.The objectives were to investigate the feasibility of concomitant administration of carboplatin, monitor acute toxicity during radiotherapy, and determine subacute side effects, such as wound healing following surgery after chemoradiotherapy. A prospective study was conducted wherein a total of 40 patients with stage III and IV squamous cell carcinomas of oral cavity, oropharynx, hypopharynx and larynx were enrolled. All patients were treated with external beam radiotherapy and weekly carboplatin area under curve (AUC of 5). Radiotherapy was given in single daily fractions of 1.8-2 grays (Gy) to a total dose of 66-72 Gy. Salvage surgery was performed for any residual or recurrent locoregional disease. Neck dissection was recommended for all patients with neck disease showing less than a complete response after chemoradiation. A total of 40 patients were enrolled of whom 32 were males and 8 were females. Highest incidence of cancer was seen in the 5th-6th decades of life with a median age of 47.7 years. Oropharyngeal tumours constituted a maximum of 21 patients followed by hypopharynx in 10, larynx in 7 and oral cavity in 2. 80% of the patients had a neck node on presentation of which 40% had N2-N3 nodal status. TNM staging revealed that 58% of patients were in stage III and 43% in stage IV. Evaluation of acute toxicity revealed that 50% had grade II mucositis, 25% grade III mucositis, 2.5% grade IV mucositis. 50% of patients had grade I skin reactions, 65% of patients had grade I thrombocytopenia, and 24% of patients had grade I anaemia. After completion of treatment 65% of patients had complete response at the primary and regional sites, and 35% of patients had a partial response of whom 23% underwent neck dissection and 5% of them underwent salvage surgery at the primary site. At the end of one year there were six deaths and four recurrences and 70% were free of disease. Concurrent chemoradiation with carboplatin provided good locoregional control for locally advanced head and neck cancers. This regimen, although toxic, is tolerable with appropriate supportive intervention. Primary site conservation is possible in many patients. Chemoradiotherapy appears to have an emerging role in the primary management of head and neck cancers.
Background: Oral cancers account for approximately 2% of all cancers diagnosed each year; however, the vast majority (80%) of the affected individuals are smokers whose risk of developing a lesion is five to nine times greater than that of non-smokers. Tobacco smoke contains numerous carcinogens that cause DNA damage, including oxidative lesions that are removed effectively by the base-excision repair (BER) pathway, in which poly (ADP-ribose) polymerase 1 (PARP-1), plays key roles. Genetic variations in the genes encoding DNA repair enzymes may alter their functions. Several studies reported mixed effects on the association between PARP-1 variants and the risk of cancer development. Till now no reported studies have investigated the association between PARP-1 variants and oral squamous cell carcinoma (OSCC) risk in an Indian population. Materials and Methods: In the present case control study 100 OSCC patients and 100 matched controls were genotyped using PARP1 single nucleotide peptides (SNP's) rs1136410 and rs3219090 using TaqMan assays. Results: The results indicated significantly higher risk with PARP1 rs1136410 minor allele "C" (OR=1.909; p=0.02942; CI, 1.060-3.439). SNP rs1136410 also showed significantly increased risk in patients with smoking habit at C/C genotype and at minor allele C. Conclusions: The PAPR-1 Ala762Val polymorphism may play a role in progression of OSCC. Larger studies with a greater number of samples are needed to verify these findings.
Pandey, Renu;Misra, Vatsala;Misra, Sri Prakash;Dwivedi, Manisha;Misra, Alok
Asian Pacific Journal of Cancer Prevention
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v.15
no.21
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pp.9171-9176
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2014
Aim: P53, the most commonly mutated tumor suppressor gene in all types of human cancer, is involved in cell cycle arrest and control of apoptosis. Although p53 contains several polymorphic sites, the codon 72 polymorphism is by far more common. There are divergent reports but many studies suggest p53 pro/pro SNP may be associated with susceptibility to developing various cancers in different regions of the world. The present study aimed to find any correlation between H. pylori infection and progression of carcinogenesis, by studying apoptosis and the p53 gene in gastric biopsies from north Indian population. Materials and Methods: A total of 921 biopsies were collected and tested for prevalence of H. pylori by rapid urease test (RUT), imprint cytology and histology. Apoptosis was studied by the TUNEL method. Analysis of p53 gene polymorphism at codon 72 was accomplished by PCR using restriction enzyme BstU1. Observation: Out of 921 samples tested 56.7% (543) were H. pylori positive by the three techniques. The mean apoptotic index (AI) in the normal group was 2.12, while gastritis had the maximum 4.24 followed by gastric ulcer 2.28, gastropathy 2.22 and duodenal ulcer 2.08. Mean AI in cases with gastric cancer (1.72) was less than the normal group. The analysis of p53 72 SNP revealed that p53 (Arg/Arg), (Pro /Arg) variant are higher (40.59% & 33.66%) as compared to p53 pro/pro variant (25.74%) inthe healthy population. Conclusions: The North Indian population harbors Arg or Pro/Arg SNP that is capable of withstanding stress conditions; this may be the reason of low incidence of gastric disease in spite of high infection with H. pylori. There was no significant association with H. pylori infection and AI. However, there is increased apoptosis in gastritis which may occur independent of H. pylori or p53 polymorphism.
Background: Recent studies have demonstrated an association between insulin growth factor (IGF) and insulin growth factor binding protein-3 (IGFBP-III) serum levels and increased risk for various cancers. However, little information is available on clinical implications of the IGF system in Indian patients with cervical cancer. This study explored associations by analyzing their expression profiles in cervical cancer cases. Materials and Methods: Totals of 50 patients with advanced cervical cancer and 40 healthy controls were enrolled. Human papillomavirus (HPV) and cervical biopsy sample were obtained from all participating women. Circulatory levels were estimated by ELISA and the tissue expression was assessed using RT-PCR and Western blotting. Results: Levels of IGF-I and II showed significant increase whereas IGFBP-III showed significant decline in all patients as compared to controls. Spearman correlation analysis between IGFs and HPV status showed significant correlations. Conclusions: We demonstrated elevated circulating levels and tissue expression of IGF-I and IGF-II in advancer cancer cervix patients, as compared with controls, with a converse trend being apparent for IGFBP-III. In future, associations of the IGF system and clinical outcome of cervical cancer patients in post treatment samples might point to significance in disease mapping as a prognostic marker after validation with a larger patient series.
Introduction: Breast cancer is the most common malignancy of women in Kashmir. This study was conducted with the objective of assessing hormone receptor positivity and its correlation with age at diagnosis, tumor size, histological grade and lymph node metastasis. Materials and Methods: 132 newly diagnosed cases of invasive breast cancer diagnosed at the Department of Pathology, SKIMS, Srinagar, J&K, were included after excluding biopsies, in-situ lesions and recurrence cases. Results: Mean age of the patients was 48.2 years, 59.1% being ${\leq}50$ years of age. Mean duration of symptoms was 6.32 months. Most lesions (65.1%) were 2-5 cm and 16.7% were ${\geq}5.0$ cm in greatest dimension. The predominant (80.3%) morphology was IDC-NOS. The majority of the cases presented as grade II (52.1%) lesions and lymph node involvement was present in 65.2%. ER and PR were positive in 66.3% and 63.4% cases, respectively, increasing with rising age. High grade lesions and larger size tumors were more likely to be ER and PR negative. No correlation was found between ER/PR status and lymph node metastasis. Conclusions: ER and PR expression in breast cancers in the current study was found to be higher than studies done in India/Asia but lower than studies conducted in the West, even on Indian/Asian immigrants. Markedly lower receptor expression in Indian/Asian studies is likely due to preanalytic variables, thresholds for positivity, and interpretation criteria. American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Immunohistochemical Testing of Estrogen and Progesterone Receptors in Breast Cancer are strongly advocated for standardization of receptor evaluation and for clinical management of breast cancer patients to provide best therapeutic options.
Najm, Mohammad Zeeshan;Akhtar, Md. Salman;Ahmad, Istaq;Sadaf, Sadaf;Mallick, Mohd Nasar;Kausar, Mohd Adnan;Chattopadhyay, Shilpi;Ahad, Amjid;Zaidi, Shuaib;Husain, Syed Akhtar;Siddiqui, Waseem Ahmad
Asian Pacific Journal of Cancer Prevention
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v.13
no.10
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pp.5113-5117
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2012
Prohibitin (PHB) is a chaperone protein which is highly conserved evolutionarily. It shows significant homology with the Drosophila cc gene which is considered important for development and differentiation of Drosophila melanogaster. Investigations have revealed an involvement of PHB in cellular proliferation and development, apoptosis, signal transduction, mitochondrial function and regulation of the estrogen and androgen receptors. Therefore, we conducted the present study to analyze mutations in the highly conserved region in Indian female breast cancer patients. Conventional PCR-SSCP and Automated DNA sequencing were performed with a total of 105 breast cancer samples along with adjacent normal tissue. Of the total, 14.2% (15/105) demonstrated a mutation status of prohibitin observed in our study population. We identified a novel missense mutation (Thr>Ser), a novel deletion of T nucleotide in an intron adjacent to intron-exon boundary and a previously determined missense mutation (Val>Ala). A statistically significant correlation was obtained which suggested that prohibitin may be associated with tumor development and/or progression of at least some proportion of breast cancers.
Assessment of perceptions of the community, the determinants and development of their behavior regarding common malignancies, helps in establishing evidence-based activities for prevention and early diagnosis of cancer. However information on this important aspect is lacking in our country. Qualitative methods were here used to obtain information through in depth interviews and Focus Group Discussions (FGDs) with all categories of identified stakeholders. Most were unaware of the activities of the cancer control program. Even the providers were not fully conversant. All respondents mentioned lack of diagnostic and treatment facilities in government, primary and secondary level facilities. Perceptions of different categories of stakeholders regarding why many community members did not attend screening camps and other services reflect the determinants of community behavior, acting independently as well as in combination. The cancer control program was thought to be restricted only to some private facilities and overcrowded government tertiary care facilities where the visits were time consuming. Almost all the facilities were considered curative oriented. Issues of supervision, monitoring and feedback were inadequately addressed by providers who were inadequately trained in many program activities. The program lacked effective planning, coordination and appropriate implementation at the grass roots level in Delhi. Social mobilization was grossly inadequate, as most of the community members were unaware of the existence of the program. Misconceptions about the risk factors, signs and symptoms, diagnosis, and treatment were common amongst community members as well as many of the providers. Thus the national cancer control program in our country needs further community participation and social mobilization. Accessibility, availability, acceptability and affordability of various preventive, curative and rehabilitative activities, as well as intersectoral coordination, training, supervision and monitoring of program activities, all need to be addressed to ensure the success of this important public health program.
Background: Little is known about the cancer screening prevalence and correlates in older adults from different racial backgrounds. In the context of heightened efforts for prevention and early diagnosis, we collected information on screening for two major types of cancers: cervical and breast cancer in order to establish their prevalence estimates and correlates among older South African women who participated in the Study of Global Ageing and Adults Health (SAGE) in 2008. Materials and Methods: We conducted a national population-based cross-sectional study with a multi-stage stratified cluster sample of 3,840 individuals aged 50 years or older in South Africa in 2008. In this analysis, we only considered the female subsample of (n=2202). The measures used included socio-demographic characteristics, health variables, anthropometric and blood pressure measurements. Multivariable regression analysis was performed to assess the association of socio-demographic factors, health variables and cancer screening. Results: Overall, regarding cervical cancer screening, 24.3% ever had a Papanicolaou (PAP) smear test, and regarding breast cancer screening, 15.5% ever had a mammography. In multivariate logistic regression analysis, younger age, higher education, being from the White or Coloured population group, urban residence, greater wealth, and suffering from two or more chronic conditions were associated with cervical cancer screening, and higher education, being from the White or Indian/Asian population group, greater wealth, having a health insurance, and suffering from two or more chronic condtions were associated with breast cancer screening. Conclusions: Cancer screening coverage remains low among elderly women in South Africa in spite of the national guideline recommendations for regular screening in order to reduce the risk of dying from these cancers if not detected early. There is a need to improve accessibility and affordability of early cervical and breast cancer screening for all women to ensure effective prevention and management of cervical and breast cancer.
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