Δευτέρα 25 Ιουλίου 2016

Curcumin inhibits cell growth and induces cell apoptosis through upregulation of miR-33b in gastric cancer

Abstract

In this work, the in vitro experiments about biological mechanisms of curcumin were conducted using the gastric cancer cell lines SGC-7901 and BGC-823. After 24-h exposure to curcumin at the concentrations of 5, 10, 15, 20, and 40 μmol/L, two cells showed the decreased proliferation and increased apoptosis abilities. Real-time PCR, Cell Counting Kit-8 (CCK-8) assay, western blotting, and cell apoptosis assay were used to further study the underlying mechanisms of curcumin. The first stage of our studies showed that curcumin affected the expression of miR-33b, which, in turn, affected the expression of the X-linked inhibitor of apoptosis protein (XIAP) messenger RNA (mRNA). Next, curcumin was also identified to regulate the proliferation and apoptosis of SGC-7901 and BGC-823 cells. Further bioinformatics analysis and luciferase reporter assays proved that XIAP was one of the target genes of miR-33b. In the next stage, SGC-7901 and BGC-823 cells were treated with 20 μL curcumin, miR-33b mimics, and small interfering RNA (siRNA) of XIAP, respectively. The results showed that curcumin had similar effects on cell growth and apoptosis as the upregulation of miR-33b and the upregulation of the siRNA of XIAP. The results that followed from the restore experiments showed that curcumin affected cell growth and apoptosis presumably by upregulating the XIAP targeting in gastric cancer. Collectively, our results indicate that curcumin-miR-33b-XIAP coupling might be an important mechanism by which curcumin induces the apoptosis of SGC-7901 and BGC-823 cells.



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Downregulation of HMGB1 by miR-34a is sufficient to suppress proliferation, migration and invasion of human cervical and colorectal cancer cells

Abstract

High mobility group box 1 (HMGB1) is a ubiquitous nuclear protein known to be highly expressed in human cervical (CaCx) and colorectal (CRC) cancers, and sustained high levels of HMGB1 contribute to tumourigenesis and metastasis. HMGB1-targeted cancer therapy is of recent interest, and there are not many studies on miRNA-mediated HMGB1 regulation in these cancers. Since miRNA-based therapeutics for cancer is gaining importance in recent years, it was of interest to predict miRNAs targeting HMGB1. Based on the identification of a potential miR-34a response element in HMGB1–3′ untranslated region (3′UTR) and an inverse correlation between HMGB1 and miR-34a expression levels in CaCx and CRC tissues, from a subset of the local population as well as a large sampling from TCGA database, experiments were performed to validate HMGB1 as a direct target of miR-34a in CaCx and CRC cells. Ectopic expression of miR-34a decreased the wild-type HMGB1–3′UTR luciferase activity but not that of its mutant in 3′UTR luciferase assays. While forced expression of miR-34a in CaCx and CRC cells inhibited HMGB1 mRNA and protein levels, proliferation, migration and invasion, inhibition of endogenous miR-34a enhanced these tumourigenic properties. siRNA-mediated HMGB1 suppression imitated miR-34a expression in reducing proliferation and metastasis-related events. Combined with the disparity in expression of miR-34a and HMGB1 in clinical specimens, the current findings would help in not only understanding the complexity of miRNA-target regulatory mechanisms but also in designing novel therapeutic interventions in CaCx and CRC.



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Knockdown of USP39 induces cell cycle arrest and apoptosis in melanoma

Abstract

The spliceosome machinery composed of multimeric protein complexes guides precursor messenger RNAs (mRNAs) (pre-mRNAs) splicing in eukaryotic cells. Spliceosome components have been shown to be downregulated in cancer and could be a promising molecular target for anticancer therapy. The ubiquitin-specific protease 39 (USP39) is essential for pre-mRNA splicing, and upregulated USP39 expression is noted in a variety of cancers. However, the role of USP39 in the development and progression of melanoma remains unclear. In the present study, USP39 expression was found to be increased in melanoma tissues compared with that in nevus tissues. USP39 silencing via lentivirus-mediated short hairpin RNA (shRNA) significantly suppressed melanoma cell proliferation, induced G0/G1 cell cycle phase arrest, and increased apoptosis in vitro. Moreover, USP39 knockdown suppressed melanoma tumor growth in a xenograft model. In addition, USP39 silencing was associated with the increased expressions of p21, p27, and Bax. Furthermore, the inhibition of USP39 expression decreased the phosphorylation of extracellular signal-regulated kinase (ERK)1/2, indicating that ERK signaling pathways might be involved in the regulation of melanoma cell proliferation by USP39. Our findings suggest that USP39 may play crucial roles in the development and pathogenesis of melanoma, and it may serve as a potential therapeutic target for melanoma.



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Disparities in psychosocial cancer care: A report from the International Federation of Psycho-Oncology Societies

Abstract

Background

The aim of the study was to understand the characteristics of the International Federation of Psycho-Oncology Societies (FPOS) and possible disparities in providing psychosocial care in countries where psycho-oncology societies exist.

Method

A survey was conducted among 29 leaders of 28 countries represented within the FPOS by using a questionnaire covering (i) characteristics of the society; (ii) characteristics of the national health care system (NHS); (iii) level of implementation of psycho-oncology and (iv) main problems of psycho-oncology in the country.

Results

Twenty-six (90%) FPOS returned the questionnaires. One-third reported to have links with and support from their government, while almost all had links with other scientific societies. FPOS varied in their composition of members' professions. Psychosocial care provision was covered by state-funded health services in a minority of countries. Disparities between countries arose from different causes and were problematic in some parts of the world (e.g. Africa, SE Asia). Elsewhere (e.g. Southern Europe, Eastern Europe), austerity policies were reportedly responsible for resource shortages with negative consequences on psychosocial cancer care. Half of FPOS rated themselves to be integrated into mainstream provision of care, although lack of funding was the most common complain.

Conclusion

The development and implementation of psycho-oncology is fragmented and undeveloped, particularly in some parts of the world. More effort is needed at national level by strong coalitions with oncology societies, better national research initiatives, cancer plans and patient advocacy, as well as by stronger partnership with international organizations (e.g. WHO, UICC).



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Κυριακή 24 Ιουλίου 2016

Primary ovarian carcinoid: A report of two cases and a decade registry

Publication date: Available online 9 July 2016
Source:Journal of the Egyptian National Cancer Institute
Author(s): Islam H. Metwally, Amr F. Elalfy, Shadi Awny, Islam A. Elzahaby, Reham M. Abdelghani
ObjectivesThis study aims at reporting 2 cases of primary ovarian carcinoid tumor, and providing an adequate registry of such cases and how they were managed.Methods2 female patients with primary ovarian carcinoid were diagnosed and treated in our center. Discussion of their presentation, pathology and treatment is entitled. Also a thorough search of all published registries and case reports of ovarian carcinoid was done with analysis of reported data.Results164 cases of primary ovarian carcinoid tumor were detected since 2005 with the predominance of the insular variant. Carcinoid syndrome occurs in nearly 14% of these cases. Most of the cases were treated with hysterectomy. Unfortunately, the prognosis was not documented in most series.ConclusionPrimary ovarian carcinoid is a relatively rare disease with an indolent course and excellent outcome. Carcinoid syndrome, especially carcinoid heart disease may worsen the prognosis. Total abdominal hysterectomy with bilateral salpingo-oophorectomy has been commonly used as the treatment of choice of primary ovarian carcinoid tumors.



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Carcinoma of Gall bladder with distant metastasis to breast parenchyma. Report of a case and review of literature

Publication date: Available online 2 July 2016
Source:Journal of the Egyptian National Cancer Institute
Author(s): Damodara Kumaran, Manikandan Anamalai, Umesh Velu, Aruna Nambirajan, Pramod Kumar Julka
BackgroundGall bladder carcinoma is one of the most common cancers in India. Gall bladder cancer with metastasis to the breast is very rare. Herein we intend to report a case of carcinoma gall bladder with breast metastasis and a short review of the literature.MethodsThis report describes an interesting and unusual case of gall bladder carcinoma presenting with breast metastasis.Case reportA 38-year lady presented with complaints of right abdominal pain. Bilateral breast examination showed 2×2cm palpable lump in the upper outer quadrant of the left breast. Contrast-enhanced CT of the abdomen and pelvis showed circumferential thickening of gall bladder with the loss of fat plane with the adjacent liver parenchyma. Biopsy from the breast lump was reported as metastatic adenocarcinoma compatible with primary in the gall bladder. Whole body PET-CT showed gall bladder mass with abdominal and pelvic nodes with metastasis to liver, left breast, C7 vertebral body and left supra-clavicular node. She was diagnosed to have disseminated carcinoma gall bladder with liver, breast and supraclavicular nodal metastasis. She received palliative chemotherapy with gemcitabine and carboplatin and radiotherapy to C7 vertebra. After receiving 3 cycles of chemotherapy, chemotherapy was changed to the second line with single agent capecitabine. In spite of two lines of chemotherapy, she succumbed to disease progression and expired.ConclusionThere are limited examples of gall bladder adenocarcinoma with simultaneous metastasis to breast in the English literature. Our case showed an unusual dissemination of gall bladder cancer.



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Prevalence of hepatocellular carcinoma in chronic hepatitis C patients in Mid Delta, Egypt: A single center study

Publication date: Available online 1 July 2016
Source:Journal of the Egyptian National Cancer Institute
Author(s): Dina H. Ziada, Sherif El Sadany, Hanan Soliman, Sherief Abd-Elsalam, Marwa Salama, Nehad Hawash, Amal Selim, Manal Hamisa, Hala M. Elsabagh
Background and aimHepatocellular carcinoma (HCC) has an increasing incidence worldwide. In this study we aimed to assess the prevalence of HCC among HCV patients in our center in Mid Delta, Egypt.Patients and methodsDuring the period between April 2013 and January 2015, we screened sequentially chronic HCV patients attending inpatient wards or outpatient Clinic of Tropical Medicine Department in Tanta University Hospital for HCC. Individuals with focal lesion in Ultrasound (US) and/or serum α-fetoprotein (AFP) level >200ng/ml were examined by triphasic computed tomography scanning (CT), and/or magnetic resonance imaging (MRI).ResultsAmong 514 HCV patients interviewed and accepted sharing in this study, 90 (17.5%), 144 (28%), and 280 (54.5%) were Child A, B, and C, respectively. We found that 108/514 patients (21%) had focal lesion detected by US. Also, 89/514 (17.3%) had elevated AFP >200, 13 of them (14.6%) had no focal lesion on US, but further work up showed HCC in 2 of them. Overall HCC diagnosis was confirmed in 103 cases, 94 of them (91.3%) were Child B or C. Occurrence of HCC was significantly higher in smokers, diabetics, patients with decompensated liver and those with positive family history of HCC. Only 20/103 (19.4%) were candidates to curative treatments, 8 of them were Child A asymptomatic and discovered accidentally during screening.ConclusionThe high prevalence of HCC in our HCV patients (22%) was mainly associated with decompensated cirrhosis. A national surveillance program for the detection of HCC in cirrhotic HCV Egyptian patients by combining ultrasound examination and AFP is highly recommended.



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