Identification of Optimal Reference Genes for Normalization of RT-qPCR Data in Cancerous and Non-Cancerous Tissues of Human Uterine Cervix.

This study aimed to identify the most stably expressed reference genes from a panel of 32 candidate genes for normalization of reverse transcription-quantitative real-time polymerase chain reaction data in cancerous and non-cancerous tissues of human uterine cervix. Overall, PUM1, YWHAZ, and RPLP0 were identified as the most stably expressed genes in paired cancerous and non-cancerous tissues. The results were further stratified by the state of malignancy of the tissues, histopathological type of the cancer, and the human papillomavirus-type.

The anti-cancer effects of Tualang honey in modulating breast carcinogenesis: an experimental animal study.

BACKGROUND: Honey has been shown to have anti-cancer effects, but the mechanism behind these effects is not fully understood. We investigated the role of Malaysian jungle Tualang honey (TH) in modulating the hematological parameters, estrogen, estrogen receptors (ER1) and pro and anti-apoptotic proteins expression in induced breast cancer in rats. METHODS: Fifty nulliparous female Sprague-Dawley rats were used and grouped as follows: Group 0 (healthy normal rats control), Group 1 (negative control; untreated rats), Groups 2, 3 and 4 received daily doses of 0.2, 1.0 and 2.0 g/kg body weight of TH, respectively. The rats in groups 1, 2, 3, 4 were induced with 80 mg/kg of 1-methyl-1-nitrosourea (MNU). TH treatment in groups 2, 3 and 4 was started one week prior to tumor induction and continued for 120 days. RESULTS: The TH-treated rats had tumors of different physical attributes compared to untreated negative control rats; the tumor progression (mean 75.3 days versus 51.5 days); the incidence (mean 76.6% versus 100%); the multiplicity (mean 2.5 versus 4 tumor masses per rat); the size of tumor mass (mean 0.41 cm versus 1.47 cm [p < 0.05]) and the weight of the tumor mass (mean 1.22 g versus 3.23 g; [p < 0.05]). Histological examinations revealed that cancers treated with TH were mainly of grades I and II compared with the non-treated control, in which the majority were of grade III (p < 0.05). TH treatment was found to modulate hematological parameters such as Hb, RBCs, PCV, MCV, RDW, MCHC, polymorphs and lymphocytes values. TH treatment groups were found to have a lower anti-apoptotic proteins (E2, ESR1 and Bcl-xL) expression and a higher pro-apoptotic proteins (Apaf-1 and Caspase-9) expression at serum and on cancer tissue level (p < 0.05). CONCLUSION: Tualang Honey alleviates breast carcinogenesis through modulation of hematologic, estrogenic and apoptotic activities in this experimental breast cancer animal model. Tualang Honey may be used as a natural 'cancer-alleviating' agent or as a supplement to chemotherapeutic agents.

Placebo Controlled Trials: Interests of Subjects versus Interests of Drug Regulators.

The use of placebo-controlled trials in situations where established therapies are available is considered ethically problematic since the patients randomised to the placebo group are deprived of the beneficial treatment. The pharmaceutical industry and drug regulators seem to argue that placebo-controlled trials with extensive precautions and control measures in place should still be allowed since they provide necessary scientific evidence for the efficacy and safety of new drugs. On the other hand, the scientific value and usefulness for clinical decision-making may be much higher if the new drug is compared directly to existing therapies. As such, it may still be unethical to impose the burden and risk of placebo-controlled trials on patients even if extensive precautions are taken. A few exceptions do exist. The use of placebo-controlled trials in situations where an established, effective and safe therapy exists remains largely controversial.

Median Survival Time of Endometrial Cancer Patients with Lymphovascular Invasion at the Hospital Universiti Sains Malaysia.

BACKGROUND: Endometrial cancer is the most common gynaecologic malignancy among females worldwide. The purpose of this study was to determine the median survival time of endometrial cancer patients at the Hospital Universiti Sains Malaysia (USM). METHODS: A list of 121 endometrial cancer cases registered at Hospital USM between 2000 until 2011 was retrospectively reviewed. The survival time of the endometrial cancer patients was estimated by Kaplan-Meier survival analysis. Log-rank tests were performed to compare the survival of the patients based on socio-demographics and clinical presentation. RESULTS: Only 108 patients, 87.0%, were included who were of Malay ethnicity. Previous history included menopause in 67.6% of patients and diabetes mellitus in 39.8% of patients; additionally, 63.4% of patients were nulliparous. Tumour staging was as follows: 24.5% stage I, 10.8% stage II, 26.5% stage III and 38.2% stage IV. The overall median survival time of the endometrial cancer patients was 70.20 months (95% confidence interval (CI): 51.79, 88.61). The significant factors were age, the presence of lymphovascular invasion and treatment received. CONCLUSION: The overall survival of endometrial cancer was low. A prospective study needs to be carried out to discover more effective and accurate tests for the early detection of endometrial cancer.

Informed Consent Template and Guidelines on the Ethical Practice in Human Genetics and Human Genomic Research; Initiatives of the Universiti Sains Malaysia.

Malaysia is advancing and nearly on pace with the international scientific community in human genetics and human genomics research. However, this research poses unique challenges. Although Malaysia already regulates medical genetic services, these regulations are insufficient for coping with the ethical issues emerging from recent genomic technologies. The Universiti Sains Malaysia recently created in-house guidelines and an informed consent template for genetic and genomic research. This article presents these guidelines and the informed consent template and discusses the justification and the background of the initiative. We also propose recommendations pertaining to local social studies and regulatory arrangements.

Review of the medicinal effects of tualang honey and a comparison with manuka honey.

Tualang honey (TH) is a Malaysian multifloral jungle honey. In recent years, there has been a marked increase in the number of studies published in medical databases regarding its potential health benefits. The honey is produced by the rock bee (Apis dorsata), which builds hives on branches of tall Tualang trees located mainly in the north-western region of Peninsular Malaysia. This review collates the results of the various studies of TH that range from research on tissue culture to randomised control clinical trials. Findings thus far show that, TH has antimicrobial, anti-inflammatory, antioxidant, antimutagenic, antitumor, and antidiabetic properties, in addition to wound-healing attributes. Some of its properties are similar to the well-researched Manuka honey (New Zealand and/or Australian monofloral honey). Distinct differences include higher phenolics, flavonoids, and 5-(hydroxymethyl) furfural (HMF). Compared with Manuka honey, TH is also more effective against some gram-negative bacterial strains in burn wounds.

Fibroblast test cells of embryo of Super Java Chicken as an indicator to test toxicity and malignancy.

Fibroblast is one component of connective tissue cells in polygonal or stellate with cytoplasmic processes or projections. In vitro, tissue culture is an excellent medium used in biomedical research. The goal of this study was to analyze Toxicity and Malignancy in Embryo of Super Java Chicken as Potential Candidates of Strong Poultry in Indonesia. This study used Preparation of fibroblast primary cell culture of Java super chicken embryos, Pathogenicity test using fibroblast cells from Super Java chicken, Toxicity test using fibroblast cells from Super Java Chicken. Primary fibroblast cell culture of Java super chicken embryos was prepared from 10-day-old brood chicken eggs free of pathogens. Cells were prepared in 96-well microplates with minimal essential medium (MEM) containing 10 % fetal calf serum (FCS) 100 IU/ug penicillin/streptomycinVirus isolates were diluted in stages from 10-2 to 10-5 and inoculated into Java Super Chicken Fibroblast cell culture. The result showed that the negative control of the samples had a faster proliferative power than the fibroblast cell culture of Java super chicken, which was treated with concentrations of 10-2; 10-3; 10-4; 10-5. Moreover, before being inoculated with the virus, the confluent fibroblast cells of Java super chicken looked oval and regular. The day after infection, syncytia (large multinucleated cells) began to form on a small scale and became more pronounced on the second and third post-infection days. CPE was found in the 10-2,10-3 and 10-4 virus dilutions, and CPE was not found in the 10-5 dilution.

Honey and cancer: sustainable inverse relationship particularly for developing nations-a review.

Honey and cancer has a sustainable inverse relationship. Carcinogenesis is a multistep process and has multifactorial causes. Among these are low immune status, chronic infection, chronic inflammation, chronic non healing ulcers, obesity, and so forth. There is now a sizeable evidence that honey is a natural immune booster, natural anti-inflammatory agent, natural antimicrobial agent, natural cancer "vaccine," and natural promoter for healing chronic ulcers and wounds. Though honey has substances of which the most predominant is a mixture of sugars, which itself is thought to be carcinogenic, it is understandable that its beneficial effect as anticancer agent raises skeptics. The positive scientific evidence for anticancer properties of honey is growing. The mechanism on how honey has anticancer effect is an area of great interest. Among the mechanisms suggested are inhibition of cell proliferation, induction of apoptosis, and cell-cycle arrest. Honey and cancer has sustainable inverse relationship in the setting of developing nations where resources for cancer prevention and treatment are limited.

Adequacy of cellular material in split-sampling of cervical scrapings for routine cancer screening: an analysis of 702 smears.

OBJECTIVE: The aim of this study was to examine cells (split-sample) that were retained on sampling devices used to collect conventional Pap smears (primary smears) in order to evaluate specimen adequacy and cytological diagnosis of scrapings that are routinely discarded. STUDY DESIGN: Cervical scrapings from women attending routine cervical cancer screening were obtained using a cervical brush. Following primary conventional smear preparation, the same sampling devices were rinsed in Preservcyt solution (Cytyc) for subsequent monolayered thin smear (split-sample/discarded sample). The smears (conventional and ThinPrep monolayer) were examined independently by pathologists and classified using the Bethesda System. The diagnoses from discarded samples (split-sample smears) were then compared with the diagnoses made on primary conventional Pap smears. RESULTS: 702 samples were studied. Cell abnormalities was found in 14/702 conventional smear and 12/702 split-sample thin smear. The adequacy of sampling in primary smears was 94.7% compared to 88.9% in split-sample smears. Six cases of Human Papillomavirus infection was found in split-sample smear, whereas only 5 cases found in primary smear. Cohen's Kappa was 0.61 showing substantial agreement between both sampling cytological results. CONCLUSION: The cervical brush discarded after conventional smear retain adequate number of cells for diagnostic purposes.

Evaluation of Effect of Honey Sugars Analogue Therapy against Breast Cancer Induced by 1-Methyl-1-nitrosourea in In Vivo Breast Cancer Model.

The use of honey as a complementary and alternative medicine is associated with vast range of therapeutic promises. It is established that it exhibits potential innumerable medicinal effects which is attributed to it phenolic, flavonoids, and other diverse compounds profile. However, the effect of honey sugars analogue as its major constituent has not been investigated. This study examined the effect of honey sugars analogue (HSA) namely fructose, glucose, maltose, and sucrose in breast cancer-induced albino Sprague-Dawley (SD) rat models. The treatment was administered when first palpable tumour reached 10-12 mm in size by dividing nulliparous rats (n = 30) into following groups: Group 0 (negative control, n = 10), Group 1 (positive control, n = 10), and Group 2 (received 1.0 g/kg body HSA, n = 10) over a period of 120 days. The effect of treatment against breast cancer was observed with a slower tumour progression, a lower median tumour size, multiplicity, and weight (p < 0.05). The anticancer effect was through amelioration of tumour growth, tumour grading, and haematological parameters. Data also show that HSA administration induces an increased susceptibility of expression of proapoptotic proteins such as Apaf-1, caspase-9, IFN-γ, IFNGR1, and p53, and a reduced expression of antiapoptotic proteins such as E2, ESR1, TNF-α, COX-2, and Bcl-xL 1 in their mechanisms of action. HSA behaves akin to honey. Thus, HSA may modulate breast cancer as an analogue or major profile of honey.

Clinicopathological comparison of adenocarcinoma of cervix and endometrium using cell cycle markers: P16ink4a, P21waf1, and p27Kip1 on 132 cancers.

OBJECTIVE: We studied the clinicopathological parameters of adenocarcinoma arising from endocervix (ECA) and from endometrium (EMA) based on the expression of P16ink4a, P21waf1, and p27Kip1 proteins. STUDY DESIGN: Immunohistochemistry was done on sections of confirmed ECA and EMA from hysterectomy specimens which have had no prior chemotherapy/radiotherapy. RESULTS: There were 40 ECAs and 92 EMAs. The mean age of ECA was 49.82 (SD 10.29); the youngest was 30 years old and the oldest 75 years old. The mean age of EMA was 54.45 (SD 10.92); the youngest was 30 years old and the oldest was 82 years old. For ECA, the size of the tumour is significantly associated with age and with depth of infiltration. FIGO stage is associated with histological grade. p21WAF1 expression is significantly associated with infiltration of the corpus and lymph node metastasis. p27Kip1 expression is significantly associated with lymph node invasion. The presence of lymph node metastasis is strongly associated when p16INK4a and p27Kip1 expressions are analyzed in combination. For EMA, p16INK4a expression is associated with histologic grade. CONCLUSION: Our study shows that we could use these cell cycle markers as predictors for more aggressive subsets of adenocarcinoma of the cervix and endometrium.

Clinacanthus nutans Standardized Fraction Arrested SiHa Cells at G1/S and Induced Apoptosis via Upregulation of p53.

INTRODUCTION: Cervical cancer is a leading cause of death in women. Current cancer treatment comes with side effects. Clinacanthus nutans has been known traditionally to treat cancer. This study was aimed to characterize C. nutans standardized fraction (SF1) and to investigate its anticancer mechanism against SiHa cells. MATERIALS AND METHODS: SF1 was produced by optimized methodology for bioassay-guided fractionation. Fourier transform infrared (FTIR) spectroscopy and liquid chromatography-mass spectrometry (LC-MS) were carried out to characterize the SF1. SF1 was screened for cytotoxicity activity toward HeLa, SiHa, and normal cells (NIH) cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. The anticancer mechanism of SF1 was evaluated toward SiHa cells, which showed highest cytotoxicity toward SF1 treatment. The mechanism includes cell cycle progression and protein expression, which was detected using specific antibody-conjugated fluorescent dye, p53-FITC, by flow cytometry. RESULTS: Major constituents of SF1 were alkaloids with amines as functional group. SF1 showed highest cytotoxic activity against SiHa (half-maximal inhibitory concentration [IC50] < 10 µg/mL) compared to HeLa cells. Cytoselectivity of SF1 was observed with no IC50 detected on normal NIH cells. On flow cytometry analysis, SF1 was able to induce apoptosis on SiHa cells by arresting cell cycle at G1/S and upregulation of p53 protein. CONCLUSION: SF1 showed anticancer activity by inducing apoptosis through arrested G1/S cell cycle checkpoint-mediated mitochondrial pathway.

Comparative study between Pap smear cytology and FTIR spectroscopy: a new tool for screening for cervical cancer.

AIMS: To evaluate Fourier transform infrared (FTIR) spectroscopy as new tool for screening of cervical cancer in comparison with cervical cytology. METHODS: A total of 800 cervical scrapings were taken by cytobrush and placed in ThinPrep medium. The samples were dried over infrared transparent matrix. Beams of infrared light were directed at the dried samples at frequency of 4000 to 400 cm(-1). The absorption data were produced using a Spectrum BX II FTIR spectrometer. Data were compared with the reference absorption data of known samples using FTIR spectroscopy software. FTIR spectroscopy was compared with cytology (gold standard). RESULTS: FTIR spectroscopy could differentiate normal from abnormal cervical cells in the samples examined. The sensitivity was 85%, specificity 91%, positive predictive value 19.5% and negative predictive value of 99.5%. CONCLUSION: This study suggests that FTIR spectroscopy could be used as an alternative method for screening for cervical cancer.

An automated cervical pre-cancerous diagnostic system.

OBJECTIVE: This paper proposes to develop an automated diagnostic system for cervical pre-cancerous. METHODS AND DATA SAMPLES: The proposed automated diagnostic system consists of two parts; an automatic feature extraction and an intelligent diagnostic. In the automatic feature extraction, the system automatically extracts four cervical cells features (i.e. nucleus size, nucleus grey level, cytoplasm size and cytoplasm grey level). A new features extraction algorithm called region-growing-based features extraction (RGBFE) is proposed to extract the cervical cells features. The extracted features will then be fed as input data to the intelligent diagnostic part. A new artificial neural network (ANN) architecture called hierarchical hybrid multilayered perceptron (H(2)MLP) network is proposed to predict the cervical pre-cancerous stage into three classes, namely normal, low grade intra-epithelial squamous lesion (LSIL) and high grade intra-epithelial squamous lesion (HSIL). We empirically assess the capability of the proposed diagnostic system using 550 reported cases (211 normal cases, 143 LSIL cases and 196 HSIL cases). RESULTS: For evaluation of the automatic feature extraction performance, correlation test approach was used to determine the capability of the RGBFE algorithm as compared to manual extraction by cytotechnologist. The manual extraction of size was recorded in micrometer while the automatic extraction of size was recorded in number of pixels. Region color was recorded in mean of grey level value for both manual and automatic extraction. The results show that the estimated size and mean of grey level have strong linear relationship (correlation test more than 0.8) with those extracted manually by cytotechnologist. Hence, the size of nucleus, size of cytoplasm and grey level of cytoplasm created very strong linear relationship with correlation test more than 0.95 (approaching one). For the intelligent diagnostic, the performance of the H(2)MLP network was compared with three standard ANNs (i.e. multilayered perceptron (MLP), radial basis function (RBF) and hybrid multilayered perceptron (HMLP)). The performance was done based on accuracy, sensitivity, specificity, false negative and false positive. The H(2)MLP network performed the best diagnostic performance as compared to other ANNs. It was able to achieve 97.50% accuracy, 100% specificity and 96.67% sensitivity. The false negative and false positive were 1.33% and 3.00%, respectively. CONCLUSIONS: This project has successfully developed an automatic diagnostic system for cervical pre-cancerous. This study has also successfully proposed one image processing technique namely the RGBFE algorithm for automatic feature extraction process and a new ANN architecture namely the H(2)MLP network for better diagnostic performance.

Prevalence and type distribution of human papillomavirus (HPV) in Malaysian women with and without cervical cancer: an updated estimate.

Information on the prevalence and type distribution of human papillomavirus (HPV) among Malaysian women is currently limited. The present study therefore aimed to provide an updated estimate on the prevalence and type distribution of HPV among Malaysian women with and without cervical cancer. Total DNA was isolated from the cervical cell specimens of 185 histopathologically confirmed cervical cancer patients and 209 cancer-free healthy females who were tested negative in a recent Pap test. Viral-specific DNA was subsequently amplified with biotinylated primers and hybridized to HPV type-specific probes via a proprietary "flow-through hybridization" process for determination of HPV genotype. It was demonstrated that 83.2% of the cervical cancer patients and none (0.0%) of the cancer-free females were positive for HPV infection. Among HPV-positive subjects, 14 different viral genotypes were observed, namely HPV16, 18, 31, 33, 35, 45, 52, 53, 58, 66/68, 73, 81, 82, and 84/26. A total of 91.6% of the HPV-positive subjects had single-type HPV infections and the remaining 8.4% were simultaneously infected by two HPV genotypes. The most common HPV infections found were HPV16 (35.7%), HPV18 (26.0%), HPV58 (9.1%), and HPV33 (7.1%) single-type infections, followed by HPV16 + HPV18 co-infections (5.2%). The study has successfully provided an updated estimate on the prevalence and type distribution of HPV among Malaysian women with and without cervical cancer. These findings could contribute valuable information for appraisal of the impact and cost-effectiveness of prophylactic HPV vaccines in the Malaysian population.

Honey as a Potential Natural Antioxidant Medicine: An Insight into Its Molecular Mechanisms of Action.

Honey clasps several medicinal and health effects as a natural food supplement. It has been established as a potential therapeutic antioxidant agent for various biodiverse ailments. Data report that it exhibits strong wound healing, antibacterial, anti-inflammatory, antifungal, antiviral, and antidiabetic effects. It also retains immunomodulatory, estrogenic regulatory, antimutagenic, anticancer, and numerous other vigor effects. Data also show that honey, as a conventional therapy, might be a novel antioxidant to abate many of the diseases directly or indirectly associated with oxidative stress. In this review, these wholesome effects have been thoroughly reviewed to underscore the mode of action of honey exploring various possible mechanisms. Evidence-based research intends that honey acts through a modulatory road of multiple signaling pathways and molecular targets. This road contemplates through various pathways such as induction of caspases in apoptosis; stimulation of TNF-α, IL-1ß, IFN-γ, IFNGR1, and p53; inhibition of cell proliferation and cell cycle arrest; inhibition of lipoprotein oxidation, IL-1, IL-10, COX-2, and LOXs; and modulation of other diverse targets. The review highlights the research done as well as the apertures to be investigated. The literature suggests that honey administered alone or as adjuvant therapy might be a potential natural antioxidant medicinal agent warranting further experimental and clinical research.

Prevalence of goblet cell metaplasia in endocervical and endometrial adenocarcinoma : a histochemical study.

To determine the prevalence of goblet cell metaplasia in endocervical and endometrial adenocarcinomas by histochemial staining and to investigate the most sensitive histochemical staining method to detect this metaplasia, a total of 90 tissue blocks representing 30 non-neoplastic cervix, 30 non-neoplastic endometrium, 30 endocervical and endometrial adenocarcinoma cases were obtained for histochemical staining with Toluidine Blue (TB), Methylene Blue (MB), Mucicarmine (MUC), Periodic Acid Schiff before and after Diastase digestion (PAS, PAS-D), Alcian Blue pH 2.5 (AB), and Periodic Acid Schiff after Alcian Blue pH 2.5 (PAB). The cases were blinded and evaluated by a pathologist [NHO] for the presence of goblet cell metaplasia, the amount of goblet cells present and the histochemical differentiation of the goblet cells compared with its surrounding glandular epithelium. Goblet cell metaplasia was present in 2 out of 30 cases in non-neoplastic cervix, 0 out of 30 cases in non-neoplastic endometrium, 7 out of 15 cases in endocervical adenocarcinoma and in 2 out of 15 cases in endometrial adenocarcinoma. Relatively few goblet cells were seen in endometrial adenocarcinoma, few to moderate amounts were seen in endocervical adenocarcinoma and relatively more goblet cells were seen in non-neoplastic cervix. The differentiation of the goblet cells with its surrounding glandular epithelium was moderate to strong in non-neoplastic cervix and endocervical adenocarcinoma, while the differentiation in endometrial adenocarcinoma was weak to moderate. The various staining methods showed differences in presence, amount and differentiation of the goblet cells. Goblet cell metaplasia of the reproductive organs is not as rare as previously reported. There was no statistical difference in presence, amount and differentiation of goblet cells according to the various cases. The must optimum staining methods for staining goblet cells in non-neoplastic cervix, endocervical adenocarcinoma and endometrial adenocarcinoma were PAS, PASD and AB.

Oral Administration of Tualang and Manuka Honeys Modulates Breast Cancer Progression in Sprague-Dawley Rats Model.

Breast cancer has been recognized as the leading cause of death in women worldwide. Research has shown the importance of complementary and alternative therapies in cancer. In this study, we investigated the antitumoural therapeutic effects of Malaysian Tualang honey (TH) and Australian/New Zealand Manuka honey (MH) against breast cancer in rats. Thirty syngeneic virgin female Sprague-Dawley (SD) rats were induced by the carcinogen 1-methyl-1-nitrosourea (MNU) 80 mg/kg. The treatment started when first palpable tumour reached 10-12 mm in size by dividing rats into following groups: Group 0 (negative control); Group 1 (positive control); and Groups 2 and 3 which received 1.0 g/kg body weight/day of TH and MH, respectively, for 120 days. The data demonstrate that cancer masses in TH and MH treated groups showed a lower median tumour size, weight, and multiplicity compared with the nontreated positive control (p < 0.05). Treatment also showed a dramatic slower growth rate (up to 70.82%) compared with the nontreated control (0%) (p < 0.05). The antitumoural effect was mediated through modulation of tumour growth, tumour grading, estrogenic activity, and haematological parameters. Our findings demonstrate that systemic administration of TH and MH increases the susceptibility of expression of proapoptotic proteins (Apaf-1, Caspase-9, IFN-γ, IFNGR1, and p53) and decreases the expression of antiapoptotic proteins (TNF-α, COX-2, and Bcl-xL 1) in its mechanism of action. This highlights a potential novel role for TH and MH in alleviating breast cancer.

Poorly differentiated thyroid carcinoma: A hospital-based clinicopathological study and review of literature.

INTRODUCTION: Poorly differentiated thyroid carcinoma (PDTC) is a rare aggressive malignancy of thyroid follicular cells and has unique features in morphology and behavior. This study was aimed to describe the experience of a tertiary medical center with PDTC within a 10-year period. MATERIALS AND METHODS: This is a descriptive retrospective study of eight cases of PDTC among 418 various thyroid carcinomas. All cases of PDTC were retrieved along with the clinicopathological information. RESULTS: Only eight cases (1.9%) of PDTC were diagnosed among 418 thyroid carcinomas. Mean age was 48.12 with 3:5 (male:female) and tumor size ranged 3-12 cm. PDTC were diagnosed coexisting with one or more other pathologies; nodular hyperplasia (four cases), papillary carcinoma (one case), follicular carcinoma (three cases), and Hashimoto thyroiditis (two cases); with ≥60% PDTC component. Six cases associated with high-grade features died within 3 years after diagnosis. DISCUSSION: Mean age in this study was younger including a 20-year-old girl. Younger age was associated with better prognosis. Most of the cases had underlying benign thyroid lesions and differentiated thyroid carcinoma. Most of the PDTC had poor prognosis associated with PDTC component ≥60%, tumor necrosis, high mitotic count, lymph node involvement, vascular invasion and distant metastasis; and these cases died within 3 years after diagnosis. CONCLUSION: Although treatment of PDTC remains surgery followed by radioiodine therapy, correct histopathological diagnosis is important for clinicians and oncologists to predict the prognosis. All thyroid carcinoma should be sampled thoroughly not to miss small foci of PDTC component.

Curcumin: the spicy modulator of breast carcinogenesis.

Worldwide breast cancer is the most common cancer in women. For many years clinicians and the researchers are examining and exploring various therapeutic modalities for breast cancer. Yet the disease has remained unconquered and the quest for cure is still going on. Present-day strategy of breast cancer therapy and prevention is either combination of a number of drugs or a drug that modulates multiple targets. In this regard natural products are now becoming significant options. Curcumin exemplifies a promising natural anticancer agent for this purpose. This review primarily underscores the modulatory effect of curcumin on the cancer hallmarks. The focus is its anticancer effect in the complex pathways of breast carcinogenesis. Curcumin modulates breast carcinogenesis through its effect on cell cycle and proliferation, apoptosis, senescence, cancer spread and angiogenesis. Largely the NFkB, PI3K/Akt/mTOR, MAPK and JAK/STAT are the key signaling pathways involved. The review also highlights the curcumin mediated modulation of tumor microenvironment, cancer immunity, breast cancer stem cells and cancer related miRNAs. Using curcumin as a therapeutic and preventive agent in breast cancer is perplexed by its diverse biological activity, much of which remains inexplicable. The information reviewed here should point toward potential scope of future curcumin research in breast cancer.