Upregulation of SMAD4 inhibits thyroid cancer cell growth via MAPK/JNK pathway repression

Purpose: To investigate whether the effect of mothers against decapentaplegic homolog 4 (SMAD4) on thyroid cancer cell survival was via the MAPK/JNK pathway. Methods: Papillary thyroid cancer (TPC)-1 cells were cultured and transfected with SMAD4 overexpression plasmid or siRNA to achieve SMAD4 overexpression or knockdown, respectively. In TPC-1 cells, the mRNA and protein expression levels of SMAD4, mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) were quantified using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. Cell viability and apoptosis were measured using MTT assay and flow cytometry, respectively. MAPK and JNK inhibitors (U0126 and SP600125) were used for rescue experiments. The sensitivity of TPC-1 cells to chemotherapeutic drugs, cisplatin and doxorubicin, was also assessed. Results: A reduction in viability and an enhancement in apoptosis (p < 0.01) were found when SMAD4 was overexpressed in TPC-1 cells. Knockdown of SMAD4 elicited opposite results (p < 0.01). Overexpression of SMAD4 caused a decrease in the activation of MAPK and JNK, as evidenced by lower levels of phosphorylated MAPK and phosphorylated JNK (p < 0.05). Results from rescue experiments indicate that the increase in cell viability after SMAD4 knockdown was reversed by MAPK/JNK inhibitors (p < 0.05 and p < 0.01). Finally, overexpression of SMAD4 increased cytotoxic susceptibility of thyroid cancer cells to cisplatin/doxorubicin. Conclusion: These results indicate that SMAD4 inhibits thyroid cancer cell growth via inactivation of MAPK/JNK pathway. Overexpression of SMAD4 also increased thyroid cancer cell sensitivity to cisplatin/doxorubicin

Facilitators of HCV treatment adherence among people who inject drugs: a systematic qualitative review and implications for scale up of direct acting antivirals

Abstract Background While the public health benefits of new HCV treatments depend on treatment adherence, particularly among people who inject drugs (PWID), several social and medical factors can jeopardize treatment adherence. The aim of this study is to examine the qualitative literature on facilitators to HCV treatment adherence among PWID. Methods We searched six databases to identify qualitative research studies on HCV treatment adherence facilitators among PWID. Two reviewers independently extracted and analyzed data using PRISMA guidelines and the CASP tool to evaluate study quality. Results From ten studies representing data from 525 participants, three major themes emerged across studies: logistical facilitators within health systems enhanced HCV treatment adherence, positive social interactions between PWID and staff provided positive feedback during treatment, and HCV treatment may complicate the addiction recovery process. Conclusions Although PWID face several barriers to adherence, we identified treatment adherence facilitators that could be incorporated into clinical practice

Exploring the Social Meaning of Curing HIV: A Qualitative Study of People Who Inject Drugs in Guangzhou, China

Our objective was to explore the social meaning of HIV and perceptions of an HIV cure among people who inject drugs (PWID) in Guangzhou, China, which speaks to ethical and resource challenges to development in this field. We conducted a qualitative research study using in-depth interviews. We analyzed interview transcripts from 29 PWID, eight physicians, and three social workers from an outpatient HIV clinic and two methadone maintenance treatment centers. The social meaning of HIV infection and perceptions of an HIV cure reflected patients' relationships with society, health systems, and physicians. First, HIV infection decreased perceived social worth and disrupted peer relationships. The possibility of being cured renewed patient hope for regaining physical well-being and achieving social mobility. However, the existence of a cure may not alter the HIV-related stigma due to its association with stigmatized behaviors and marginalized groups. Second, although stigma was a significant barrier to engagement in health care, hope for a cure may outweigh fears of stigma and enhance linkage to HIV testing and treatment as well as methadone services. A cure may exacerbate perceived health disparities if inaccessible to key affected populations such as PWID. The social implications of an HIV cure among this key affected population may inform the design and implementation of cure clinical trials. Careful management of patient expectations, focusing research on key affected populations, expanding HIV testing and treatment systems, improving access to harm reduction programs, and ensuring post-trial access are important considerations for HIV cure research