Background: Pediatric acute lymphoblastic leukemia (pALL) patients at King Abdulaziz Medical City represent a pure Saudi Arabian population. ETV6-RUNX1 positive pALL patients have good prognosis as compared to ETV6-RUNX1 negative counterparts. Therefore, frequencies of these two patient groups have a huge consideration in treatment strategies of pALL in a given population. Different geographical locations have been reported to have different frequencies of ETV6-RUNX1 ranging from 10% in Southeast Asia to 30% in Australia. Aim: Therefore, the objective of this study was to establish the ETV6-RUNX1 status of Saudi Arabian pALL patients and its association with clinical parameters and early remission. Materials and Methods: Clinical parameters and ETV6-RUNX1 status (using FISH technique) of pALL patients attending the Pediatric Oncology Clinic, King Abdulaziz Medical City, Riyadh from 2006 to 2011 were studied. Comparisons between ETV6-RUNX1 positive and negative groups were accomplished using chi-square test or Fisher's exact test. All statistical analyses were performed using SAS version 9.2 (SAS Institute, Inc., Cary, NC). Results: Out of 54 patients, 33 were male and 21 were females (ratio 1.57:1). B- and T-cell lineages were found in 47 (87%) and 7 (13%) patients respectively. Only 5 (9.3%) patients were ETV6-RUNX1 positive while 49(80.7%) were ETV6-RUNX1 negative. All ETV6-RUNX1 patients (100%) were of B-cell lineage and 80% (4/5) were in the 3-7 year age group. None of the ETV6-RUNX11 patients had ${\geq}5%$ blasts (no remission) at day 14 as compared with 9% in the ETV6-RUNX1 negative group (Figure 1). Conclusions: Frequency of ETV6-RUNX1 positive patients (less than 10%) in our pALL patients is much lower than reported for most European countries, North America, Australia and Japan while it is in accordance with ETV6-RUNX1 frequencies from Egypt (11.6%), Pakistan (10%), Spain (2%) and India (5-7%). This shows ethnic differences in genetics of pALL as well as higher frequencies of ETV6-RUNX1 positive pALL mostly in more industrialized countries, probably due to some industrial pollutants or westernized lifestyle.
Background: This pilot study looked into the physical, social, psychological and economic issues of Indian adult cancer survivors. Materials and Methods: Assumed cancer free patients, after cancer directed therapy (CDT), were assessed on the basis of a questionnaire developed by the investigators. The mental status of the survivors was elicited by modified MINI international neuro-psychiatric interview. This cross sectional assessment was conducted as a direct interaction with each patient for 30 to 45 minutes at a cancer hospital in 2012. Results: Thirty one adult cancer survivors participated in this study. Median age was 53 years with a median follow up duration of 21.8 months (Range 2.3-194.1 months). The majority (68%) did not receive financial support for treatment. Median interval after CDT to start of activity of daily living was 1.5 months (range: 0-24 months). Fatigue and loss of appetite were reported by 52% and 29% respectively. The cancer diagnosis and its treatment adversely impacted the financial condition in 42% of patients. Nineteen percent each showed social anxiety and post-traumatic stress disorder and another 13% patients reported depression. Conclusions: This prospective assessment highlights survivorship issues and the need to address those issues particularly in the context of developing countries where resources and manpower are limited.
Background: Breast cancer is by far the most frequent cancer of women (23% of all cancers), ranking second overall when both sexes are considered together. Since there has been change in clinico-pathological factors and treatment profiles for breast cancer patients over the years, the present study to evaluate the change trends in India. Materials and Methods: A detailed analysis was carried out with respect to age, menopausal status, family history, disease stage, surgery performed, histopathology, hormone receptor status, and use of chemotherapy or hormonal therapy. Change in various clinico-pathological factors and treatments of breast cancer cases was recorded and analysed. Results: Mean age at presentation was found to be earlier in 2005-2006 compared with 1997-98 (p value: 0.046). More premenopausal women were diagnosed with breast cancer in 2005-2006 when this was compared with initial years of assessment (p value ${\leq}0.001$). When change in the receptor status was evaluated, we observed that there was a decrease in cases of ER and PR receptor positivity which was significant (p value: 0.007). Over the period of time, more f patients were not offered surgery initially in view of advanced disease when the two time periods were compared (p value: ${\leq}0.001$). There was a significant increase in patients who were initially offered neo-adjuvant chemotherapy in view of advanced disease at presentation (p value: ${\leq}0.001$). There was increasing number of patients who received palliative treatment for symptoms in 2005-2006 when compared to patients treated in 1997-98((p value: ${\leq}0.001$). Conclusions: Changes in mean age at presentation, premenopausal status, and stage at presentation have occurred over the years. More aggressive patterns of disease have become more common with early age at presentation and aggressive biological behaviour with receptor negative tumours.
Background: Breast cancer is the most common malignancy of women in the world. The disease is caused by infectious and non-infectious, environmental and lifestyle factors. Tobacco smoke has been one of the most widely studied environmental factors wiith possible relevance to breast cancer. The purpose of this study was to assess the impact of tobacco smoking in breast cancer patients in a hospital based cohort and to establish prognostic implications if any. Materials and Methods: A retrospective audit of 100 women with pathological diagnosis of invasive breast cancer was included in this study. The verbal questionnaire elicited information on current and previous history of exposure to smoking in addition to active smoking. All analyses were adjusted for potential confounders, including stage at presentation, alcohol intake, hormonal replacement therapy, oral contraceptive intake, obesity and menopausal status. Results: The mean age at presentation of breast cancer was $51.4{\pm}10.86$ years. Mean age of presentation was $53.1{\pm}11.5$ and $45.7{\pm}11.9$ years in never smokers and passive smokers, respectively. Age at presentation varied widely in patients exposed to tobacco smoke for >10 years in childhood from $40.3{\pm}12.0$ years to $47.7{\pm}13.9$ in patients exposed for > 20years as adults. Among passive smokers, 60.9% were premenopausal and 39.1% of patients were postmenopausal. In never smokers, 71.4% were post menopausal. Expression of receptors in non-smokers vs passive smokers was comparable with no significant differences. Metastatic potential in lung parenchyma was slightlyelevated in passive smokers as compared to never smokers although statistically non-significant. Conclusions: An inverse relationship exists between the intensity and duration of smoking and the age at presentation and poor prognostic factors. The results strongly suggest efforts should be taken to prevent smoking, encourage quitting and restrict exposure to second hand smoke in India.
Background: NSCLC is a disease involving uncontrolled cell growth, which could result in metastases into nearby tissues beyond the lungs. Materials and Methods: The aim of the present study was to analyze the influence of epidermal growth factor receptor (EGFR) gene expression on metastasis and survival in NSCLC patients. The present case-control study included 100 cases of NSCLC patients and 100 age and sex matched controls. EGFR gene expression was analyzed by quantitative real time PCR using serum RNA. Association with NSCLC patient survival was analyzed by the Kaplan-Meier method. Results: We analyzed EGFR gene expression and observed mean increased gene expression of 13.5 fold in NSCLC patients. Values reflected overall survival of patients with a median of 15.8 months in the cases of <13 fold increased gene expression vs 6.7 months with >13 fold increased EGFR gene expression (p=0.005). Distant metastatic patients with <13 fold increased EGFR gene expression had 7.9 months of median survival time while>13 fold increased EGFR gene expression had only 5 months of median survival time (p=0.03). Non metastatic patients with <13 fold increased EGFR gene expression had 18 months of median survival time as compared to only 7.1 months with >13 fold increased expression. Conclusions: Higher cell free EGFR mRNA expression may play an important role in causing distant metastases and reducing overall survival of NSCLC patients in the Indian population.
Hulikal, Narendra;Ray, Satadru;Thomas, Joseph;Fernandes, Donald J.
Asian Pacific Journal of Cancer Prevention
/
제13권12호
/
pp.6087-6091
/
2012
Context: Patients diagnosed with a cancer have a life time risk of developing another de novo malignancy depending on various inherited, environmental and iatrogenic risk factors. Of late the detection of new primary has increased mainly due to refinement in both diagnostic and treatment modalities. Cancer victims are surviving longer and thus are more likely to develop a new metachronous malignancy. Aims: To report our observed trend of increase in prevalence of both synchronous and metachronous second malignant neoplasms among cancer victims and to review the relevant literature. Settings and Design: A hospital based retrospective collection of prospective data of patients diagnosed with second denovo malignancy. Materials and Method: The study was conducted over a 5 year period from July 2008 to June 2012. All patients diagnosed with a histologically proven second malignancy as per Warren Gate's criteria were included. Various details regarding sex, age at presentation, synchronous or metachronous, treatment and outcome were recorded. Conclusions: The occurrence of multiple primary malignancies is not rare. Awareness of the possibility alerts the clinician in evaluation of patients with a known malignancy presenting with unusual sites of metastasis. Individualizing the treatment according to the stages of the primaries will result in durable cancer control particularly in synchronous double malignancy.
Background: A retrospective analysis of all cancer patients attending the radiotherapy outpatient department (OPD) of a single unit during the period of January 2005 till December 2006 was conducted to know the geographical distribution and incidence of the most common cancers, their stage of presentation, treatment compliance among the patients and follow-up. Materials and Methods: A total of 4,484 patients were registered in the Institute of Medical Sciences, Banaras Hindu University during the period of January 2005-December 2006; of which 1,975 registered in an individual unit were included for the retrospective analysis. Results: Most of the patients hailed from the various districts of UP and Bihar. Females outnumbered males with a ratio of 1.33:1. Females mostly belonged to the age group of 40-59 years; whilst males were a decade older. Major cancer sites in females were cervix and breast followed by head and neck. Leading cancer sites in males were head and neck, brain, bone, soft tissue and lung. Most of the cases presented in advanced stage of disease (74%). Squamous cell carcinoma was the most common histopathology (56%). A significant proportion of patients defaulted after undergoing preliminary investigations (16%). Only 53.9% of females and 58.5% of males took treatment out of which 68% and 63% completed the prescribed treatment. Compliance with follow-up was poor. Conclusions: The outcome of this study will significantly help us to define region specific strategies needed for cancer management in eastern Uttar Pradesh.
Purpose: The aim of this study was to investigate the prognostic significance of the CD56+NK-TIL count in infiltrating ductal carcinoma (IDC) of breast. Material and Methods: Immunohistochemistry (IHC) was performed using antibodies specific for CD56 on formalin-fixed and paraffin-embedded tissue sections of 175 infiltrating ductal carcinomas (IDC) of breast. Distribution of intratumoral and stromal CD56+NK-TILs was assessed semi-quantitatively. Results: A low intratumoral CD56+count showed significant and inverse associations with tumor grade, stage, and lymph node status, whereas it had significant and direct association with response to treatment indicating good prognosis. These patients had better survival (${\chi}^2$=4.80, p<0.05) and 0.52 fold lower death rate (HR=0.52, 95% CI=0.28-0.93) as compared to patients with high CD56+ intratumoral count. The association of survival was insignificant with low CD56 stromal count as compared to high CD56 stromal count (${\chi}^2$=1.60, p>0.05). Conclusion: To conclude, although NK-TIL count appeared as a significant predictor of prognosis, it alone may not be sufficient for predicting the outcome considering the fact that there exists a crosstalk between NK-TILs and the other immune infiltrating TILs.
Background: Sperm DNA damage is underlying aetiology of poor implantation and pregnancy rates but also affects health of offspring and may also result in denovo mutations in germ line and post fertilization. This may result in complex diseases, polygenic disorders and childhood cancers. Childhood cancer like retinoblastoma (RB) is more prevalent in developing countries and the incidence of RB has increased more than three fold in India in the last decade. Recent studies have documented increased incidence of cancers in children born to fathers who consume alcohol in excess and tobacco or who were conceived by assisted conception. The aetiology of childhood cancer and increased disease burden in these children is lin ked to oxidative stress (OS) and oxidative DNA damage( ODD) in sperm of their fathers. Though several antioxidants are in use to combat oxidative stress, the effect of majority of these formulations on DNA is not known. Yoga and meditation cause significant decline in OS and ODD and aid in regulating OS levels such that reactive oxygen speues meditated signal transduction, gene expression and several other physiological functions are not disrupted. Thus, this study aimed to analyze sperm ODD as a possible etiological factor in childhood cancer and role of simple life style interventions like yoga and meditation in significantly decreasing seminal oxidative stress and oxidative DNA damage and thereby decreasing incidence of childhood cancers. Materials and Methods: A total of 131 fathers of children with RB (non-familial sporadic heritable) and 50 controls (fathers of healthy children) were recruited at a tertiary center in India. Sperm parameters as per WHO 2010 guidelines and reactive oxygen species (ROS), DNA fragmentation index (DFI), 8-hydroxy-2'-deoxy guanosine (8-OHdG) and telomere length were estimated at day 0, and after 3 and 6 months of intervention. We also examined the compliance with yoga and meditation practice and smoking status at each follow-up. Results: The seminal mean ROS levels (p<0.05), sperm DFI (p<0.001), 8-OHdG (p<0.01) levels were significantly higher in fathers of children with RB, as compared to controls and the relative mean telomere length in the sperm was shorter. Levels of ROS were significantly reduced in tobacco users (p<0.05) as well as in alcoholics (p<0.05) after intervention. DFI reduced significantly (p<0.05) after 6 months of yoga and meditation practice in all groups. The levels of oxidative DNA damage marker 8-OHdG were reduced significantly after 3 months (p<0.05) and 6 months (p<0.05) of practice. Conclusions: Our results suggest that OS and ODD DNA may contribute to the development of childhood cancer. This may be due to accumulation of oxidized mutagenic base 8OHdG, and elevated MDA levels which results in MDA dimers which are also mutagenic, aberrant methylation pattern, altered gene expression which affect cell proliferation and survival through activation of transcription factors. Increased mt DNA mutations and aberrant repair of mt and nuclear DNA due to highly truncatred DNA repair mechanisms all contribute to sperm genome hypermutability and persistant oxidative DNA damage. Oxidative stress is also associated with genome wide hypomethylation, telomere shortening and mitochondrial dysfunction leading to genome hypermutability and instability. To the best of our knowledge, this is the first study to report decline in OS and ODD and improvement in sperm DNA integrity following adoption of meditation and yoga based life style modification.This may reduce disease burden in next generation and reduce incidence of childhood cancers.
Snakebite is a severe medical, economic, and social problem across the world, mostly in the tropical and subtropical area. These regions of the globe have typical of the world's venomous snakes present where access to prompt treatment is limited or not available. Snake venom is a complex mixture of toxin proteins like neurotoxin and cardiotoxin, and other enzymes like phospholipase A2 (PLA2), haemorrhaging, transaminase, hyaluronidase, phosphodiesterase, acetylcholinesterase, cytolytic and necrotic toxins. Snake venom shows a wide range of biological effects like anticoagulation or platelet aggregation, hemolysis, hypotension and edema. Phospholipase A2 is the principal constituent of snake venom; it catalyzes the hydrolysis of the sn-2 position of membrane glycerophospholipids to liberate arachidonic acid, which is the precursor of eicosanoids including prostaglandins and leukotrienes. The information regarding the structure and function of the phospholipase A2 enzyme may help in treating the snakebite victims. This review article constitutes a brief description of the structure, types, mechanism occurrence, and tests of phospholipase A2 and role of components of medicinal plants used to inhibit phospholipase A2.
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