Socio-demographic correlates of betel, areca and smokeless tobacco use as a high risk behavior for head and neck cancers in a squatter settlement of Karachi, Pakistan

BACKGROUND: Head and neck cancers are a major cancer burden in Pakistan. They share a common risk factor profile including regular consumption of products of betel, areca and tobacco. Use of paan, chaalia, gutka, niswar and tumbaku is acceptable in Pakistan and is considered a normal cultural practice. This cross-sectional study was carried out to understand the relation of socio-demographic factors for the consumption of paan, chaalia, gutka, niswar and tumbaku in Pakistani population. Through systematic sampling, 425 subjects from a squatter settlement in Karachi were interviewed using a structured questionnaire. High risk behavior was defined as Daily use of any of the above products. RESULTS: Daily use of all the substances except chaalia was higher among males compared to females. Chaalia use was higher among adolescents than adults while non-married consumed both chaalia and gutka more than married. Mohajir ethnicity had higher prevalence of paan, gutka and tumbaku use while Pathans had higher prevalence of niswar use. CONCLUSION: Prevalence of use of chewable products is high in Pakistan with particularly high use of certain substances related with socio-demographic profiles. Industrially prepared products, chaalia and gutka, are gaining popularity among youth. Policies and focused interventions can be developed taking into consideration the preferred use of products among different socio-demographic groups

The Wnt inhibitory factor 1 restoration in prostate cancer cells was associated with reduced tumor growth, decreased capacity of cell migration and invasion and a reversal of epithelial to mesenchymal transition

<p>Abstract</p> <p>Background</p> <p>Aberrations in the Wnt pathway have been reported to be involved in the metastasis of prostate cancer (PCa) to bone. We investigated the effect and underlying mechanism of a naturally-occurring Wnt inhibitor, WIF1, on the growth and cellular invasiveness of a bone metastatic PCa cell line, PC3.</p> <p>Results</p> <p>The WIF1 gene promoter was hypermethylated and its expression down-regulated in the majority (7 of 8) of PCa cell lines. Restoration of WIF1 expression in PC-3 cells resulted in a decreased cell motility and invasiveness via up-regulation of epithelial markers (E-cadherin, Keratin-8 and-18), down-regulation of mesenchymal markers (N-cadherin, Fibronectin and Vimentin) and decreased activity of MMP-2 and -9. PC3 cells transfected with WIF1 consistently demonstrated reduced expression of Epithelial-to-Mesenchymal Transition (EMT) transcription factors, Slug and Twist, and a change in morphology from mesenchymal to epithelial. Moreover, WIF1 expression significantly reduced tumor growth by approximately 63% in a xenograft mouse model. This was accompanied by an increased expression of E-cadherin and Keratin-18 and a decreased expression of vimentin in tumor tissues.</p> <p>Conclusion</p> <p>These data suggest that WIF1 regulates tumor invasion through EMT process and thus, may play an important role in controlling metastatic disease in PCa patients. Blocking Wnt signaling in PCa by WIF1 may represent a novel strategy in the future to reduce metastatic disease burden in PCa patients.</p

Dkk-3, a Secreted Wnt Antagonist, Suppresses Tumorigenic Potential and Pulmonary Metastasis in Osteosarcoma

Osteosarcoma (OS) is the most common primary bone malignancy with a high propensity for local invasion and distant metastasis. Despite current multidisciplinary treatments, there has not been a drastic change in overall prognosis within the past 2 decades. Dickkopf-3 protein (Dkk-3/REIC) has been known to inhibit canonical Wnt/β-catenin pathway, and its expression has been shown to be downregulated in OS cell lines. Using in vivo and in vitro studies, we demonstrated that Dkk-3-transfected 143B cells inhibited tumorigenesis and metastasis in an orthotopic xenograft model of OS. Inoculation of Dkk-3-transfected 143B cell lines into nude mice showed significant decreased tumor growth and less metastatic pulmonary nodules (88.7%) compared to the control vector. In vitro experiments examining cellular motility and viability demonstrated less anchorage-independent growth and decreased cellular motility for Dkk-3-transfected 143B and SaOS2 cell lines compared to the control vector. Downstream expressions of Met, MAPK, ALK, and S1004A were also downregulated in Dkk-3-transfected SaOS2 cells, suggesting the ability of Dkk-3 to inhibit tumorigenic potential of OS. Together, these data suggest that Dkk-3 has a negative impact on the progression of osteosarcoma. Reexpressing Dkk-3 in Dkk-3-deficient OS tumors may prove to be of benefit as a preventive or therapeutic strategy

The efficiency of intra-articular injection of silver nanoparticles (AgNPs) on repair of experimentally induced avascular meniscal tear in dogs

Meniscal tears in the inner avascular area have been reported as a common cause of disability in dogs that associated with failure of healing process due to their limited vascularity. In spite of various sterategies were reported for treatment of such tears, their clinical use was limited. Therefore, different biomaterials have been assessed to stimulate regeneration of avascular meniscal tears. Currently, silver nanoparticles (AgNPs) enormously involved in biomedicine including tissue regeneration, drug delivary, and antibacterial applications. Thus, AgNPs was fabricated in the present study to investigate its potential to induce and support meniscal healing process in an avascular meniscal tear model. The nanomaterial was synthesized and characterized using transmission electron microscope (TEM). Next, a full thickness longitudinal meniscal tear was created in the avascular zone and either left empty or treated with AgNPs. &nbsp;Animals were monitored clinically at weeks 3, 6, 9, and 12 weeks after surgery for lameness parameters including lameness during walking, pain on manipulation, range of motion, and functional disability. Additionally, the harvested menisci were examined macroscopically and histologically at 4, 8, and 12 weeks. The designed material revealed improved clinical outcomes compared to control group. The gross and histological observations proved that the meniscal healing was stimulated in the AgNPs-treated group in comparison to control one, where the AgNPs-treated tear sites were filled with reparative tissue. In conclusion, AgNPs nanomaterial has a promoting effect on the process of meniscal tissue healing in the avascular region, proving that AgNPs is a promising material for meniscal tissue regeneration

Comparison between the regenerative potential of bone marrow aspirate (BMA) and platelet-rich plasma (PRP) on healing of canine meniscal tear

Repair of meniscal tears in the avascular zone represents an obstacle for orthopedic surgeons. Several therapeutic methods have been suggested to mange these tears including meniscectomy and meniscal allografts; however, their clinical application was restricted due to their disadvantages. These limitations inspired the necessity to develop products that possess the ability to initiate healing in such avascular tears. Hence, the goal of the current study is to assess and compare the regenerative capability of bone marrow aspirate (BMA) and platelet-rich plasma (PRP) to enhance repair of avascular meniscal tears. After preparation of BMA and PRP, meniscal tear was conducted in the inner avascular zones in dogs and left untreated as control or treated with either BMA or PRP. Clinical observation of weight bearing, lameness, pain on manipulation, gait, and functional disability were investigated after 3, 6, 9, and 12 weeks of surgery. In addition, gross and histological evaluations were performed at weeks 4, 8, and 12 after surgery. Both materials demonstrated a positive improvement in clinical observations compared to the control group. Furthermore, repair of meniscal tears was stimulated in tears treated with either BMA or PRP with better gross and histological outcomes in PRP-treated group than BMA-treated group. To conclude, our findings showed that BMA and PRP possess the potential to enhance the healing process of meniscal tears in the inner avascular region with the superiority of PRP

Chewing of betel, areca and tobacco: perceptions and knowledge regarding their role in head and neck cancers in an urban squatter settlement in Pakistan

The link of betel, areca and chewable tobacco with head and neck cancers is clearly established. Fifty eight percent of the global head and neck cancers occur in South and Southeast Asia, where chewing of betel, areca and tobacco are common. This study was carried out to establish the pattern of use of Paan, Chaalia, Gutka, Niswar, Tumbaku and Naas among population of squatter settlement of Karachi and to determine the perceptions and knowledge regarding their role in the etiology of head and neck cancers. It was a cross-sectional study, performed at Bilal colony in Karachi. Through systematic sampling, 425 subjects [a male and female from a household] were interviewed with a structured questionnaire. Knowledge regarding etiology of head and neck cancers was classified in ordinals of ‘good’, ‘some’ and ‘poor’, for each substance separately, while practices were classified into ‘daily user’, ‘occasional user’ and ’never user’. About 40% of the participants were chewing at least one item [betel, areca or tobacco products] on daily basis. This prevalence was 2.46 times higher among males than females and 1.39 times higher among adolescents than adults. At least 79% of the participants were classified as having poor knowledge about the carcinogenicity of each of these items. Knowledge increased with age and level of education. Health hazards of these items were poorly recognized and about 20% perceived at least one of these items to be beneficial. Positive attitudes were seen regarding the steps to curb the production, business and consumption of these substances. In conclusion, prevalence of chewing of betel, areca and tobacco among adults and adolescent is high. Deficiency inknowledge and wrong perception of favorable effect of chewing products is common. Besides curtailing the availability of chewing products, correct knowledge regarding its ill-effects should be inculcated among population to decrease the burden of head and neck cancers

Neuropilin-2 expression is inhibited by secreted Wnt antagonists and its down-regulation is associated with reduced tumor growth and metastasis in osteosarcoma

Background: Neuropilin 2 (NRP2) isa multi-functional co-receptor to many receptors, including VEGF receptor, c-Met and others. NRP2 has recently been implicated in tumor angiogenesis, growth, and metastasis of many other cancers. However, its role in osteosarcoma remains poorly understood. Results: NRP2 was overexpressed in osteosarcoma cell lines and tissues, and associated with poor survival of osteosarcoma patients. Knockdown of NRP2 expression by short-hairpin (Sh) RNA resulted in reduced tumor growth, metastasis, and blood vessel formation of osteosarcoma. Knockdown of NRP2 expression by ShRNA also inhibited the recruitment of HUVEC cells to osteosarcoma cells. Inhibition of Wnt signaling by overexpression of secreted Wnt antagonists soluble LRP5, Frzb, and WIF1 markedly down-regulated mRNA and protein expression of NRP2 in osteosarcoma cell lines. Conclusions: Regulation of NRP2 receptor expression may represent a novel approach for treatment of osteosarcoma through retarding osteosarcoma growth, metastasis and blood vessel formation. In addition, down-regulation of NRP2 expression can be achieved by expression of secreted Wnt antagonists.NCATS NIH HHS [UL1 TR001414]SCI(E)[email protected]

Dkk-3, a Secreted Wnt Antagonist, Suppresses Tumorigenic Potential and Pulmonary Metastasis in Osteosarcoma

Osteosarcoma (OS) is the most common primary bone malignancy with a high propensity for local invasion and distant metastasis. Despite current multidisciplinary treatments, there has not been a drastic change in overall prognosis within the past 2 decades. Dickkopf-3 protein (Dkk-3/REIC) has been known to inhibit canonical Wnt/β-catenin pathway, and its expression has been shown to be downregulated in OS cell lines. Using in vivo and in vitro studies, we demonstrated that Dkk-3-transfected 143B cells inhibited tumorigenesis and metastasis in an orthotopic xenograft model of OS. Inoculation of Dkk-3-transfected 143B cell lines into nude mice showed significant decreased tumor growth and less metastatic pulmonary nodules (88.7%) compared to the control vector. In vitro experiments examining cellular motility and viability demonstrated less anchorage-independent growth and decreased cellular motility for Dkk-3-transfected 143B and SaOS2 cell lines compared to the control vector. Downstream expressions of Met, MAPK, ALK, and S1004A were also downregulated in Dkk-3-transfected SaOS2 cells, suggesting the ability of Dkk-3 to inhibit tumorigenic potential of OS. Together, these data suggest that Dkk-3 has a negative impact on the progression of osteosarcoma. Reexpressing Dkk-3 in Dkk-3-deficient OS tumors may prove to be of benefit as a preventive or therapeutic strategy

Dkk-3, a Secreted Wnt Antagonist, Suppresses Tumorigenic Potential and Pulmonary Metastasis in Osteosarcoma

Osteosarcoma (OS) is the most common primary bone malignancy with a high propensity for local invasion and distant metastasis. Despite current multidisciplinary treatments, there has not been a drastic change in overall prognosis within the past 2 decades. Dickkopf-3 protein (Dkk-3/REIC) has been known to inhibit canonical Wnt/β-catenin pathway, and its expression has been shown to be downregulated in OS cell lines. Using in vivo and in vitro studies, we demonstrated that Dkk-3-transfected 143B cells inhibited tumorigenesis and metastasis in an orthotopic xenograft model of OS. Inoculation of Dkk-3-transfected 143B cell lines into nude mice showed significant decreased tumor growth and less metastatic pulmonary nodules (88.7%) compared to the control vector. In vitro experiments examining cellular motility and viability demonstrated less anchorage-independent growth and decreased cellular motility for Dkk-3-transfected 143B and SaOS2 cell lines compared to the control vector. Downstream expressions of Met, MAPK, ALK, and S1004A were also downregulated in Dkk-3-transfected SaOS2 cells, suggesting the ability of Dkk-3 to inhibit tumorigenic potential of OS. Together, these data suggest that Dkk-3 has a negative impact on the progression of osteosarcoma. Reexpressing Dkk-3 in Dkk-3-deficient OS tumors may prove to be of benefit as a preventive or therapeutic strategy