Impact of Low BMI and Nutritional Status on Quality of Life and Disease Outcome in Breast Cancer Patients: Insights From a Tertiary Cancer Center in India.

This study investigates the impact of Body Mass Index (BMI) on Quality of Life (QoL) and treatment outcomes in breast cancer (BC) patients, particularly focusing on underweight individuals with compromised nutritional status. A nonrandomized prospective study comprising 121 newly diagnosed patients across various BMI categories utilized FACT-B & FACIT-Sp-12 questionnaires. Follow-ups occurred at baseline, during (3rd and 6th), and after (12th month) anthracycline-taxane chemotherapy, either sequentially or concomitantly. Patients with low BMI (<18.5 kg/m2; 53.7%) exhibited significantly poorer QoL, marked by compromised nutritional indicators (low MUAC and SFT). Repeated measures ANOVA identified significant correlations between BMI groups in functional, social, and emotional QoL aspects (p < 0.05), with no notable differences in other domains. A Chi-square (ꭓ2) test underscored a significant link between BMI and treatment response (p < 0.0001), showing higher rates of non-responders among underweight patients (p = 4.259e-14). The study advocates pretreatment consultation with a dietitian as standard care for Indian BC patients, offering complimentary nutritional support for improved QoL outcomes and treatment responses.

Orchestrated expression of vasculogenic mimicry and laminin-5γ2 is an independent prognostic marker in oral squamous cell carcinoma.

Vasculogenic mimicry (VM), an endothelial cell-independent alternative mechanism of blood supply to the malignant tumour, has long been considered as an adverse prognostic factor in many cancers. The correlation of VM with laminin-5γ2 and the assessment of their harmonized expression as an independent risk factor have not been elucidated yet in oral squamous cell carcinoma (OSCC). CD31/PAS staining stratified 116 clinically diagnosed OSCC specimens into VM+ and VM- cohorts. The expression pattern of laminin-5γ2 and its upstream modulator MMP2 was evaluated by immunohistochemistry and Western blot. The Kaplan-Meier and Cox regression analyses were performed to assess the survival and prognostic implications. The presence of VM demonstrated a significant correlation with the expression of laminin-5γ2 (p < .001) and MMP2 (p < .001). This pattern was mirrored by the significant upregulation of laminin-5γ2 and MMP2 in VM+ cohorts compared with the VM- ones. Furthermore, co-expression of VM and laminin-5γ2 was significantly associated with tumour grade (p = .010), primary tumour size (p < .001), lymph node metastasis (p = .001) and TNM stages (p < .001) but not with patients' age, gender, tobacco and alcohol consumption habit. Vasculogenic mimicry and laminin-5γ2 double-positive cohort displayed a significantly poorer disease-free survival (DFS) and overall survival (OS). Vasculogenic mimicry, laminin-5γ2 and their subsequent dual expression underlie a significant prognostic value for DFS [hazard ratio (HR) = 9.896, p = .028] and OS [HR = 21.401, p = .033] in OSCC patients. Together, our findings imply that VM along with laminin-5γ2 is strongly linked to the malignant progression in OSCC and VM and laminin-5γ2 coordination emerges as a critical prognostic biomarker for OSCC.

Assessment of quality of life among advanced ovarian cancer patients in a tertiary care hospital in India.

PURPOSE: The study aims to record the quality of life (Qol) and its changes while ovarian cancer (OC) patients undergo debulking surgeries and chemotherapy in a tertiary care hospital of Eastern India. METHODS: Patients with advanced epithelial OC (FIGO stages III-IV) were recruited. They underwent primary/interval debulking surgeries with classical chemotherapy (adjuvant/neoadjuvant) of intravenous tri-weekly doses of paclitaxel + carboplatin. QoL was assessed using Fact- O + FACIT-Sp-12 questionnaire with a set of 51 questions in different domains (spiritual, physical, social, emotional, and functional factors) and a special set for OC patients under the heading "Additional concerns." The responses from patients were recorded at baseline (diagnosis/study entry), 2, 4, and 6 months during the treatment visits. Overall survival (OS) was assessed using Kaplan Meier curve. RESULTS: A majority of patients were 49.15±10.8 years of age, school-educated (54%), unemployed/homemakers (73.5%), belonging from rural setup (64.6%) with a monthly income of Rs. 2000/- to Rs. 5000/-. There was no statistically significant (p>0.05) improvement found in Qol from the baseline till the end of the study, neither overall nor in subsets (responders (Rs)/partial responders (PRs)/non-responder (NRs) groups or the adjuvant and neoadjuvant chemotherapy groups). The common toxicities like anemia, constipation, and weight loss were significantly (p<0.05) correlated with the patients' physical, functional, emotional, and social well-being. CONCLUSION: Ovarian cancer patients represent a poor functional, social, and disease-specific quality of life that needs to be addressed, identified, and improved by the growing nexus of healthcare providers and researchers.

Phosphorylation of EphA2 receptor and vasculogenic mimicry is an indicator of poor prognosis in invasive carcinoma of the breast.

PURPOSE: The occurrence of vasculogenic mimicry (VM) and EphA2-mediated tumour progression are associated with poor prognosis in various solid tumours. Here, we aimed to investigate the prognostic implications of VM and its association with phosphorylated EphA2 receptor in invasive carcinoma of the breast. METHODS: The patients were stratified based on CD-31/PAS dual staining and subsequently the expression status of phospho-EphA2 (S897), FAK, phospho-ERK1/2 and Laminin 5Ƴ2 was analysed by immunohistochemistry. Survival of patients was correlated within the stratified cohort. RESULTS: The pathologically defined VM phenotype and phospho-EphA2 (S897) expression status were significantly associated with lower disease-free survival (DFS) and overall survival (OS). Both the features were also found to be significantly associated with higher nodal status, poor Nottingham Prognostic Index (NPI) and were more prevalent in the triple-negative breast cancer (TNBC) group. Incidentally, there were no significant association between age of the patient, grade and size of the tumour with VM and phospho-EphA2 (S897). The effector molecules of phospho-EphA2 (S897) viz., Focal Adhesion Kinase (FAK), phospho-ERK1/2 and Laminin 5Ƴ2 were significantly upregulated in the VM-positive cohort. Survival analysis revealed that the VM and phospho-EphA2 (S897) dual-positive cohort had poorest DFS [mean time = 48.313 (39.992-56.633) months] and OS [mean time = 56.692 (49.055-64.328) months]. Individually, VM-positive [Hazard Ratio (HR) 6.005; 95% confidence interval (CI) 2.002-18.018; P = 0.001 for DFS and HR 11.654; 95% CI 3.195-42.508; P < 0.0001 for OS] and phospho-EphA2 (S897)-positive (HR 4.342; 95% CI 1.717-10.983; P = 0.002 for DFS and HR 5.853; 95% CI 1.663-20.602; P = 0.006 for OS) expression proved to be independent indicators of prognosis. CONCLUSION: This study evaluated tumour dependency on oncogenic EphA2 receptor regulation and VM in invasive carcinoma of the breast and their prognostic significance. Significant correlations between VM, phospho-EphA2 and several clinicopathologic parameters of breast cancer were found. Subsequently, the occurrence of VM or phospho-EphA2 expression proved to be major contributors for poor prognosis in patients with breast cancer but their simultaneous expression failed to be an independent risk factor.

Cannabis smoke can be a major risk factor for early-age laryngeal cancer--a molecular signaling-based approach.

Epidermal growth factor receptor (EGFR) and its downstream elements are overexpressed in most cases of the head and neck squamous cell carcinoma. This study investigated the expression pattern of key proteins linked to the EGFR pathway in laryngeal carcinoma patients with a history of cannabis smoking. We selected 83 male glottic cancer patients, aged between 45 to 75 years with three distinct populations-nonsmoker, cigarette smoker, and cannabis smoker. Immunohistochemical staining was performed for EGFR, protein kinase B (PKB or Akt), nuclear factor kappa B p50 (NF-КB), and cyclooxygenase-2 (COX-2) followed by boolean scoring for statistical analysis. Experimental data showed upregulation of the selected EGFR cascade in tumor cells, stromal expression of EGFR, and nuclear localization of COX-2 in metaplastic gland cells of laryngeal cancer tissue sample. Statistical analyses indicated that overexpression of the EGFR cascade is significantly correlated to cannabis smoking. Cannabis smokers had higher expression (p < 0.01) of these onco-proteins with respect to both nonsmokers as well as cigarette smokers. Risk factor analysis showed high risk of these proteins expression in age <60 years (odds ratio (OR) > 1.5) as the lower age group had relatively higher number of cannabis smokers. This study provides evidence for a direct association between cannabis smoking and increased risk of laryngeal cancer. Higher expression of the EGFR cascade in cannabis smokers revealed that cannabis smoking may be a major cause for the early onset of aggressive laryngeal cancer.

Copy number variation of Chikungunya ECSA virus with disease symptoms among Indian patients.

After a gap of three decades, from 2005 onwards, a series of Chikungunya virus (CHIKV) outbreaks occurred worldwide. This study was performed to detect CHIKV infection, its genotype among symptomatic Eastern Indian patients and to analyze any association between the presence of CHIKV genome in patient body with appearance of disease symptoms (n = 199). Plasma-extracted viral RNA was reverse transcribed to cDNA and PCR-amplified followed by agarose gel electrophoresis. Viral load among CHIKV-positive patients was determined by real time RT-PCR. CHIKV-IgM in sera was detected by ELISA. Sequencing and phylogenetic analysis of plasma-extracted PCR products was done. CHIKV genome and IgM were detected among 65.3% (n = 130) and 41.2% (n = 82) patients respectively. Joint swelling was significantly associated with CHIKV infection (P-value: 0.0003). CHIKV PCR positive patients were grouped in two categories: Group-I: viral load <10(4) copies/ml and Group-II: viral load ≥10(4) copies/ml. Higher number of acute stage patients clustered in Group-II. Fever and joint swelling were significantly more prevalent among Group-II patients, whereas rash and diarrhoea among Group-I patients (P-value <0.05). Patient-isolated CHIKV sequences clustered with CHIKV ECSA genotypes in the phylogenetic tree, with two types of CHIKV strains found to circulate among them-as indicated by their different nucleotide sequences. This is the first study detecting the presence of CHIKV ECSA genotype among Eastern Indian patients. Fever and joint swelling might have appeared first followed by rash, diarrhea during disease progression-as indicated by CHIK viral load in patients. Thus, viral load can be used as unique diagnostic and prognostic marker of Chikungunya disease pathogenesis.

Clinical Profile and Prognostic Markers of Acute on Chronic Liver Failure (ACLF): A Single-center Experience from East India.

Aim: The aim of the study was to study the clinical profile of acute on chronic liver failure (ACLF) and establish Cell-free DNA (Cf DNA) as a predictor of the outcome of ACLF. Methods: In this prospective study, those patients who fulfilled EASL criteria were included. Cf DNA was estimated in 30 patients and compared with the CLIF-C ACLF score. Results: The median age of 132 consecutive ACLF patients was 40 years. The most common acute insult were sepsis (30.3%) and alcohol (22%). While alcohol (35.6%) and chronic HBV (14.3%) were the most common etiologies of cirrhosis. The overall mortality was 45.5% and 71.2% at 28 days and 90 days, respectively. Multiple regression analysis using the Cox proportional hazard model showed that heart rate (HR 1.06, 95% CI 1.04-1.08 P = 0.001), lung failure (HR 2.82, 95% CI 1.24-6.44, P = 0.02), and cell-free DNA (HR 2.70, 95% CI 1.17-6.24, P = 0.02) were independent predictors of mortality When Cf DNA was used to predict 28-day mortality, Cf DNA was found to have a higher AUC (AUROC 0.84, 95% CI 0.70-0.98, P = 0.001) than the CLIF-C-ACLF score (AUROC 0.81, 95% 0.66-0.97, P = 0.003). However, when 90-day mortality was compared, CLIF-C-ACLF score had a higher area under the curve (AUROC 0.93, 95% CI 0.83-1.00, P = 0.0001) than Cf DNA (AUROC 0.89, 95% CI 0.77-1.00, P = 0.0001). Conclusions: Alcohol and sepsis remain the most common causes of acute insult. Cf DNA is a better predictor of 28-day mortality, whereas CLIF-C ACLF is more accurate to predict 90-day mortality.

An assessment of childhood cancer care services in India - gaps, challenges and the way forward.

Background: Childhood cancers are emerging as an essential concern in India where there is lack of a specific programme component or policy to address childhood cancer control. There is limited information on the status and quality of childhood cancer care services in India. This paper describes the childhood cancer care services available at secondary and tertiary-level hospitals in India through a cross sectional study design. Methods: The survey was conducted in 137 tertiary-level and 92 secondary-level hospitals in 26 states and 4 Union Territories (UTs), ensuring a uniform representation of public and private care hospitals. The study tool collected data on the organisational infrastructure, type of oncology services, health workforce, equipment, treatment and referral protocols, and treatment guidelines. Descriptive statistics was used to primarily present the health service status and data on childhood cancer care services in proportions and mean. Findings: A dedicated pediatric oncology department was available in 41.6% of the public, 48.6% of private, and 64% Non Government Organization (NGO) managed tertiary-level hospitals. In 36 (39%) of the 92 hospitals providing secondary care, childhood cancer care was provided. The availability of bone (41.5%) and positron emission tomography (PET) scans (25.9%) was lower in public tertiary hospitals, whereas histopathology, computerised tomography (CT scan), and magnetic resonance imaging (MRI) were lower in public secondary hospitals than private and NGO managed hospitals for the corresponding level of care. Most tertiary hospitals had the required supportive care facilities except for play therapy and hospice care. Less than 50% of the public tertiary hospitals had stocks of the four categories of cancer-treating drugs and essential infrastructure for radiotherapy and chemotherapy. Most secondary-level hospitals not treating childhood cancer had referral linkages with tertiary hospitals. Interpretation: The situational analysis of childhood cancer care services in India showed the concentration of availability of childhood cancer care services at the tertiary level of health care. There were gaps in the availability of specialised pediatric oncology care in all the tertiary hospitals. The availability of childhood cancer care services was higher in private and NGO-managed hospitals than in public hospitals. Integration of childhood cancer as a part of the national cancer control response should be taken up as a matter of priority. The need of the hour is to formulate a childhood cancer policy that will enable timely access to care universally. Funding: World Health Organization, India provided funding and technical support.

Understanding the Correlation between Metabolic Regulator SIRT1 and Exosomes with CA-125 in Ovarian Cancer: A Clinicopathological Study.

Background: Ovarian cancer (OvCa), the deadliest gynaecological malignancy, is associated with poor prognosis and high mortality rate. Ovarian cancer has been related with CA-125 and metabolic reprogramming by SIRT1 leading to metastasis with the involvement of exosomes. Methods: Clinicopathological data of OvCa patients were collected to perform the analysis. Patients' samples were collected during surgery for immunohistochemistry and flow cytometric analysis of SIRT1, HIF-1α, exosomal markers (CD81 and CD63), ki-67, and PAS staining for glycogen deposition. Adjacent normal and tumor tissues were collected as per the CA-125 levels. Results: CA-125, a vital diagnostic marker, has shown significant correlation with body mass index (BMI) (P = 0.0153), tumor type (P = 0.0029), ascites level, ascites malignancy, degree of dissemination, tumor differentiation, FIGO stage, TNM stage, laterality, and tumor size at P < 0.0001. Since significant correlation was associated with BMI and degree of dissemination, as disclosed by IHC analysis, metabolic marker SIRT1 (P = 0.0003), HIF-1α (P < 0.0001), exosomal marker CD81 (P < 0.0001), ki-67 status (P = 0.0034), and glycogen deposition (P <0.0001) were expressed more in tumor tissues as compared to the normal ones. ROC analysis of CA-125 had shown 327.7 U/ml has the best cutoff point with 82.4% sensitivity and specificity of 52.3%. In addition, Kaplan-Meier plots of CA-125 (P < 0.0001), BMI (P = 0.001), degree of dissemination (P < 0.0001), and ascites level (P <0.0001) reflected significant correlation with overall survival (OS). Upon multivariate Cox-regression analysis for overall survival (OS), BMI (P = 0.008, HR 1.759, 95% CI 1.156-2.677), ascites malignancy (P = 0.032, HR 0.336, 95% CI 0.124-0.911), and degree of dissemination (P = 0.004, HR 1.994, 95% CI 1.251-3.178) were significant proving to be independent indicators of the disease. Conclusion: Clinicopathological parameters like BMI, degree of dissemination, and ascites level along with CA-125 can be prognostic factors for the disease. Levels of CA-125 can depict the metabolic and metastatic factors. Thus, by targeting SIRT1 and assessing exosomal concentrations to overcome metastasis and glycogen deposition, individualized treatment strategy could be designed. In-depth studies are still required.

Evaluation of numerical rating scale and neuropathic pain symptom inventory pain scores in advanced ovarian carcinoma patients undergoing surgery and first-line chemotherapy.

BACKGROUND AND AIM: Advanced epithelial ovarian cancer (OC) has a high disease manifestation with difficult-to-manage symptoms that limit the patients' functionality. Abdominal pain, persistent back pain, and neuropathic pain are among the common discomforts associated with OC and its treatment. Our study aims to determine pain scores in advanced OC patients undergoing surgery and chemotherapeutic treatment with carboplatin and paclitaxel. METHODS: One hundred and ten patients with advanced epithelial OC were enrolled and treated with surgery and an adjuvant/neoadjuvant chemotherapy regimen of carboplatin-paclitaxel for six cycles (triweekly). Pain intensity was analyzed using the validated numerical rating scale for resting, movement, sleep interference-associated pain, and neuropathic pain scores were evaluated using the neuropathic pain symptom inventory scale. Pain was correlated with Qol according to Fact-O questionnaires. Chemo-response was evaluated using the CA125 blood biomarker and CT scan of the abdomen and thorax. Data were recorded at baseline, 2, 4, and 6 months of the six chemotherapy cycles. RESULTS: Of the 110 patients, no statistically significant differences were found in pain at baseline and after treatment (P > 0.05) and between the responder and non-responder categories (P > 0.05). However, movement-associated pain had a significant correlation with chemo-response and a strong positive correlation with the patients' physical and functional wellbeing. There were more chemo-induced neuropathy occurrences (P = 0.001) in the neoadjuvant chemotherapy group. CONCLUSION: Patients in the neoadjuvant chemotherapy arm experienced more chemo-induced neuropathy that was persistent and did not improve with the treatment. RELEVANCE FOR PATIENTS: Peripheral neuropathy is a common adverse effect of platinum and taxane chemotherapeutic drugs that persists throughout cancer treatment and in survivorship. This research provides evidence that chemotherapy-associated neuropathy affects Qol of patients and it will be helpful to improve pain and palliative care management policies.

Psorinum therapy in treating stomach, gall bladder, pancreatic, and liver cancers: a prospective clinical study.

We prospectively studied the clinical efficacy of an alternative cancer treatment "Psorinum Therapy" in treating stomach, gall bladder, pancreatic and liver cancers. Our study was observational, open level and single arm. The participants' eligibility criteria included histopathology/cytopathology confirmation of malignancy, inoperable tumor, and no prior chemotherapy or radiation therapy. The primary outcome measures of the study were (i) to assess the radiological tumor response (ii) to find out how many participants survived at least 1 year, 2 years, 3 years, 4 years and finally 5 years after the beginning of the study considering each type of cancer. Psorinum-6x was administered orally to all the participants up to 0.02 ml/Kg body weight as a single dose in empty stomach per day for 2 years along with allopathic and homeopathic supportive cares. 158 participants (42 of stomach, 40 of gall bladder, 44 of pancreatic, 32 of liver) were included in the final analysis of the study. Complete tumor response occurred in 28 (17.72%) cases and partial tumor response occurred in 56 (35.44%) cases. Double-blind randomized controlled clinical trial should be conducted for further scientific exploration of this alternative cancer treatment.

Premalignant and malignant lesions of oral cavity in eastern India: a hospital-based study.

BACKGROUND: Oral carcinoma and precancers are major public health challenges in India and other developing countries. OBJECTIVES: Aim of the study was to assess the associations of demographic characteristics, addictions, chief complaints of mouth/oral and clinical diagnosis by cytology smear and punch biopsy in early detection of oral premalignant and malignant lesions. Methods Study was designed on retrospective data of case files of CDC, CNCI, Kolkata, from patients attended from January 1996 to September 2016. History was taken, histopathology and Pap smear were performed. Descriptive statistical analysis, cross-tabulation and Pearson's Chi-square test were done. RESULTS: Total participants (n = 692); 110 (15.9%) having history of swallowing betel leaf, nut lime, dokta, jarda, catecheu with an average of 11 years. Three hundred twenty-five (46.9%) had multiple addiction (cigarette/bidi/tobacco/all). Ninety-eight (12.1%), 99 (12.2%) and 68 (8.4%) were addicted to cigarette, bidi and chewing tobacco, respectively. Twenty-nine participants were addicted to alcohol; 18 (2.6%) and 11 (1.5%) took country and foreign alcohol correspondingly. Clinicians thoroughly examined lips (4.1%), buccal mucosa (27.3%), gingival (2.8%), tongue (23.1%), hard and soft palate (4.9%), mouth loor (5.2%) and other parts (32.3%); diagnosed participants as normal (22.8%)/benign (23.1%)/premalignant (39.1%)/malignant (14.8%). Smears confirmed 60, 131, 42, 9 and 8 cases as carcinoma, mild, moderate, severe dysplasia and inflammation, respectively. The punch biopsy identified 11 carcinomas, two severe, two moderate and seveeen mild dysplasia's. Chi-square test showed significant association between smear and examination (P = 0.022), diagnosis and examinations of the oral cancer patients (P = 0.0001). CONCLUSION: The study provided strong evidence that betel leaf, chewing tobacco, smoking and alcohol are independent risk factors for oral cancer. Cytological smear and biopsy are cost-effective approaches for early detection.

Naphthalimide based novel organoselenocyanates: finding less toxic forms of selenium that would retain protective efficacy.

A series of naphthalimide based organoselenocyanates were synthesized and screened for their toxicity as well as their ability to modulate several detoxifying/antioxidative enzyme levels at a primary screening dose of 3 mg/kg b.w. in normal Swiss albino mice for 30 days. Compound 4d showed highest activity in elevating the detoxifying/antioxidant enzymes levels.

Sociodemographic factors and clinical presentation of women attending Cancer Detection Centre, Kolkata for breast examination.

BACKGROUND: Breast cancer is the most common cancer in Indian women. AIM: The aim of the study was to report the sociodemographic factors, habits, personal history, gynecological and obstetric history, the clinical presentation of Indian women, and analyze those factors with the diagnosis of breast cancer. METHODS: This study is based on retrospective data collection from case files of women who attended the Cancer Detection Centre during January1995-September 2016. RESULTS: Data analysis for 1196 women showed 31.5% aged between 26 and 35 years; 90.7% were Hindus; 61.3% school-educated; 77.0% housewives/unemployed; 80.6% married and 98.2% were non-vegetarian. Physical activity, medical history and gynecologic history of menarche, menstrual type, menopause, marital age, and breast feeding history had a strong correlation with clinical diagnosis (p<0.05). About 8.4% of the total population was diagnosed with breast cancer using smear cytology, FNAC, mammography, and USG. CONCLUSIONS: Age, lack of proper education, marital status, food habit, physical activity, age of menarche, menstrual type, menopause, marital age, and breastfeeding history were highlighted as significant risk factors of breast cancer in Indian women. Smears from nipple discharges, FNAC, mammography, and USG are effective methods for breast cancer detection in low-cost setting where routine organized screening programs are not available. RELEVANCE FOR PATIENTS: The study will identify important risk factors among women in the Eastern region of India. Thus, background information of patients can be used to emphasize the importance of organizing breast cancer screening while making public health policies and implementing breast cancer control programs.

Lead and cadmium exposure induces male reproductive dysfunction by modulating the expression profiles of apoptotic and survival signal proteins in tea-garden workers.

The aim of this study was to evaluate the impact of Lead (Pb) and Cadmium (Cd) exposure at the molecular level on the reproductive status of tea garden workers in North-East India. Using semen samples, we experimentally determined sperm analysis as well as oxidative stress parameters in all samples and evaluated the expression levels of apoptotic and cell survival proteins [p53, phospho-Akt, nuclear factor-κB (NF-κB, p50 subunit) and B cell lymphoma 2 (Bcl2)]. Our data revealed significant differences in the average heavy metal concentrations and various semen analysis profile between the infertile and normal groups. Increasing Pb and Cd concentrations in semen samples of patients showed positive associations with increasing number of multiple defects in sperm and the level of seminal oxidative stress markers in the high Pb and Cd concentration groups. These groups also exhibited positive correlations between high metal concentrations and the average p53 expression levels, but negative correlations with the mean p-Akt cascade protein levels in sperm cells. In the low Pb and Cd concentrations groups, we also observed reverse mean range and correlation patterns. Therefore, our findings may suggest that graded levels of metal exposure significantly influence the relative fluctuation in the levels of p53 and Akt cascade proteins in the sperm cells of infertile subjects. Furthermore, this may be a regulating factor of sperm cell fate, in turn, determining the fertility outcome of the men working in the tea gardens.

Tea polyphenols epigallocatechin gallete and theaflavin restrict mouse liver carcinogenesis through modulation of self-renewal Wnt and hedgehog pathways.

The aim of this study is to evaluate chemopreventive and therapeutic efficacy of tea polyphenols epigallocatechin gallete (EGCG) and theaflavin (TF) on self-renewal Wnt and Hedgehog (Hh) pathways during CCl4/N-nitosodiethylamine-induced mouse liver carcinogenesis. For this purpose, the effect of EGCG/TF was investigated in liver lesions of different groups at pre-, continuous and post initiation stages of carcinogenesis. Comparatively increased body weights were evident due to EGCG/TF treatment than carcinogen control mice. Both EGCG and TF could restrict the development of hepatocellular carcinoma at 30th week of carcinogen application showing potential chemoprevention in continuous treated group (mild dysplasia) followed by pretreated (moderate dysplasia) and therapeutic efficacy in posttreated group (mild dysplasia). This restriction was associated with significantly reduced proliferation, increased apoptosis, decreased prevalence of hepatocyte progenitor cell (AFP) and stem cell population (CD44) irrespective of EGCG/TF treatments. The EGCG/TF could modulate the Wnt pathway by reducing ß-catenin and phospho-ß-catenin-Y-654 expressions along with up-regulation of sFRP1 (secreted frizzled-related protein 1) and adenomatosis polyposis coli during the restriction. In case of the Hh pathway, EGCG/TF could also reduce expressions of glioma-associated oncogene homolog 1 (Gli1) and SMO (smoothened homolog) along with up-regulation of PTCH1 (patched homolog 1). As a result, in Wnt/Hh regulatory pathways decreased expressions of ß-catenin/Gli1 target genes like CyclinD1, cMyc and EGFR/phospho-EGFR-Y-1173 and up-regulation of E-cadherin were seen during the restriction. Thus, the restriction of liver carcinogenesis by EGCG/TF was due to reduction in hepatocyte progenitor cell/stem cell population along with modulation of Wnt/Hh and other regulatory pathways.

Resveratrol Alleviates Cadmium-Induced Damage and Overexpression of Epidermal Growth Factor Receptor and its Downstream Signaling Proteins in the Reproductive System of Male Swiss Albino Mice.

Nowadays, exposure to heavy metals and their detrimental effects in humans are grave health concerns. In this study, we investigated the protective effect of resveratrol (RES) against CdCl2 (cadmium chloride)-induced impairment of spermatogenesis, histopathological alterations, and the up-regulation of epidermal growth factor receptor (EGFR) signaling cascade in Swiss albino mice. Two different doses of CdCl2 were injected intraperitoneally into two groups of mice, and in the third group RES was administered orally before injecting CdCl2 (3 times/wk) for 14 days. Sperm motility, count, vitality, and morphology were analyzed. Hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), and western blot analyses were performed on testis tissue. In CdCl2-administered animals, significant perturbations of spermatogenesis and histoarchitecture of seminiferous tubules were observed. p-EGFR, p-AKT, AKT1/2/3, NF-κß (p50), and COX-2 of the EGFR cascade were up-regulated. Although there was significant negative correlation between percentage of motile cells and protein expression, we found positive correlation between morphologically abnormal cells and overexpression of proteins in CdCl2-only treated groups. Marked improvement of sperm parameters and histopathological damages as well as down-regulation of the EGFR signaling cascade were observed in the RES-pretreated mice. Hence, the present study elucidates that RES protects against CdCl2-induced perturbation of spermatogenesis and overexpression of EGFR and its downstream signaling proteins.

Deletion in chromosome 11 and Bcl-1/Cyclin D1 alterations are independently associated with the development of uterine cervical carcinoma.

PURPOSE: The aim of this study was to understand whether there is any association between specific deleted regions in chromosome 11 (chr.11) and alteration (amplification/rearrangement) of Bcl-1/Cyclin D1 locus, located at 11q13, in uterine cervical carcinoma (CA-CX). METHODS: The deletion mapping of chr.11 was studied using 17 highly polymorphic microsatellite markers in 65 primary uterine cervical lesions. The Bcl-1/Cyclin D1 alterations were analyzed by Southern blot and/or polymerase chain reaction (PCR) method in respective cervical lesions. RESULTS: Chr.11 deletion was found to be significantly associated with progression of CA-CX. High frequency (48-65%) of deletion was found in 11p15.5 (D1), 11q22.3-23.1(D2), and 11q23.3-24.1(D3) regions and significant association was seen among deletions in D2 and D3 regions. Bcl-1/Cyclin D1 locus alteration was observed in overall 27% cervical lesions. Co-amplification of Bcl-1/Cyclin D1 locus was seen in 10% samples. However, no association was found between the deleted regions and Bcl-1/Cyclin D1 locus alterations. CONCLUSIONS: Our study suggests that there is no co-operativity between the deleted regions (D1- D3) in chr.11 and Bcl-1/Cyclin D1 alterations, but these alterations may provide cumulative effect in progression of the tumor. The D1-D3 regions may harbor candidate tumor suppressor gene(s) (TSGs) associated with the development of CA-CX.

Paediatric retinoblastoma in India: evidence from the National Cancer Registry Programme.

BACKGROUND: Globally, retinoblastoma is the most common primary intraocular malignancy occurring in children. This paper documents the recent incidence rates of retinoblastoma by age and sex groups from the Population Based Cancer Registries (PBCRs) of Bangalore, Mumbai, Chennai, Delhi and Kolkata using the data from the National Cancer Registry Programme. MATERIALS AND METHODS: Relative proportions, sex ratio, method of diagnosis, and incidence rates (crude and age standardized) for each PBCR and pooled rates of the five PBCRs were calculated for the years 2005/06 to 2009/10. Standard errors and 95% confidence limits of ASIRs by sex group in each PBCR were calculated using the Poisson distribution. Standardised rate ratios of ASIR by sex group and rate ratios at risk were also calculated. RESULTS: The maximum retinoblastoma cases were in the 0-4 age group, accounting for 78% (females) and 81% (males) of pooled cases from five PBCRs. The pooled crude incidence rate in the 0-14 age group was 3.5 and the pooled ASIR was 4.4 per million. The pooled ASIR in the 0-4, 5-9 and 10-14 age group were 9.6, 2.0 and 0.1 respectively. The M/F ratio in Chennai (1.9) and Bangalore PBCRs (2.0) was much higher than the other PBCRs. Among the PBCRs, the highest incidence rate in 0-4 age group was found in males in Chennai (21.7 per million), and females in Kolkata (18.9 per million). There was a distinct variation in incidence rates in the PBCRs in different geographic regions of India.

Analysis of different deleted regions in chromosome 11 and their interrelations in early- and late-onset breast tumors: association with cyclin D1 amplification and survival.

Previous studies have shown that younger women exhibit more aggressive pathologic features of breast cancer (BC) in comparison to older women; young age could be an independent predictor of adverse prognosis. In order to find any existing differences in the molecular progression of BC in both younger and older women, chromosome 11 (chr.11) was taken as a tool, due to its frequent deletion and amplification, particularly of CyclinD1 (CCND1) locus in BC. In the present work, the comparative analysis in the frequency of deletion in different regions in chr.11 and CCND1 amplification in BC in the two age groups was studied, as well as the interrelation and prognostic significance of these chromosomal alterations. The chr. 11 alterations were also studied in types of breast lesions other than carcinoma to see the prevalence of the alterations in these diseases. For this purpose, comparative deletion mapping of chr.11 using 17 microsatellite markers and CCND1 amplification was examined in 30 early-onset (40 years) breast carcinomas, as well as 11 other types of breast lesions. The frequency of deletion and CCND1 amplification was much higher in carcinomas than with other types of breast lesions. A total of six highly deleted regions, namely, 11p15.5, 11p11.2, 11q13.2, 11q22.3-23.1, 11q23.3-24.1, and 11q25, were identified in carcinomas of the two age groups. The 11q13.2 deletion and CCND1 amplification was comparatively higher in the carcinoma of younger women. The following significant associations were observed for (a) LOH at 11q25 with LOH at 11q13.2, 11q22.3-23.1, 11q23.3-24.1 and CCND1 amplification, respectively, and (b) LOH at 11p15.5 with LOH at 11q22.3-23.1 in carcinoma of younger women. On the other hand, the significant associations in older women were (a) LOH at 11q25 with LOH at 11q22.3-23.1, 11q23.3-24.1, respectively, and (b) LOH at 11q22.3-23.1 with LOH at 11q23.3-24.1. Deletion at 11q13.2 was also associated with reduced overall survival in the younger group, indicating its prognostic significance. It is evident from our data that the pattern of chromosomal alterations are not exactly same in the carcinomas in the two age groups. Differential interrelationship of the chromosomal alterations and prognosis in these two age groups indicate that the molecular pathogenesis of the carcinomas is not similar.