Skeletal events of Anastrozole versus Tamoxifen on bone mineral density and bone biomarker osteocalcin in postmenopausal women with early breast cancer

Objective： Postmenopausal women with breast cancer are at increased risk of bone loss because of age related estrogen deficiency face which accelerated with the use of aromatase inhibitors （AIs）. We aimed to study the effect on bone mineral density （BMD） and bone formation biomarker osteocalcin level in postmenopausal breast cancer patients, for the first three years of adjuvant hormonal treatment of both groups Tamoxifen versus Anastrozol. Methods： One-hundered postmenopausal breast cancers were prospectively randomized to receive either Tamoxifen 20 rag/day （n = 50） or Anastrozole 10 mg （n = 50）. Both BMD and osteocalcin were assessed initially before treatment and then at regular intervals for both groups. Results： Use of Tamoxifen was associated with significant annual decrease in osteocalcin （P = 0.001）, whereas Anastrozole group had gradual increase of the annual levels （P 〈 0.01）. BMD decreased significantly in Anastrozole versus Tamoxifen groups （2.6% vs. 0.4%, P 〈 0.001）. Osteoporosis T 〈 -2.5 was reported significantly higher in Anastrozole group （P 〈 0.01）. Women with initial osteopenia in Anastrozole group showed significant decrease in BMD （P 〈 0.05）. The addition of bisphosphonate for patients with early osteoporosis markedly improved both osteocalcin level and BMD. Conclusion： Tamoxifen preserves BMD in postmenopausal breast cancer patients, whereas Anastrozole accelerates age associated fall in BMD especially in the first year of therapy, moreover, the addition of bisphosphonate can help to decrease the skeletal related events associated with treatment to ensure better quality of life with treatment.

Assessment of maintenance oral Etoposide following induction chemotherapy with gemcitabine and cisplating in chemonaive extensive small cell lung cancer

Objective： The aim of our study was to evaluate the response and tolerability to treatment when using gemcitabine-cisplatin combination （GC）, followed by maintenance therapy of oral etoposide for non-progressive patients in trial to improve progression free survival and overall survival. Methods： Thirty nine patients with extensive small cell lung cancer （SCLC） and ECOG ≤ 2 received 4 cycles of chemotherapy consisting of gemcitabine 1000 mg/m^2 （day 1 and 8） cisplating 75 mgim2 （day 1） every three weeks. Twenty seven non-progressive patients after 4 cycles of chemotherapy were randomized either to receive oral etoposide 50 mg/m^2 for consecutive 15 days every 3 weeks vs no therapy for three months or progression. Results： Thirty nine eligible patients treated with GC, 27 non progressive patients were subsequently randomized to oral etoposide or observation. Median follow-up was 18 months. The overall response rate to GC was 59% and toxicity to oral etoposide was mild. There was improvement in median progression-free survival （PFS） favoring the maintenance arm of 10.5 months vs 7 months （P 〈 0.05）. Median overall survival （OS） had improved towards the maintenance arm （13 vs 11.5 months）. One year survival （60% vs 24%）, 18 months survival （20% vs 5%） favoring the maintenance. Multivariate analysis revealed that age, performance status, maintenance therapy, and response to treatment were independent prognostic factors for OS. Age, maintenance therapy, and response to treatment were highly significant factors for PFS. Conclusion： Gemcitabine-cisplatin is an effective and tolerable regiment for extensive disease of SCLC. The addition of 3 months of oral etoposide in non progressing patients was associated with a significant improvement of PFS and longer OS.

Validation of a serum microRNA panel as biomarkers for early diagnosis of hepatocellular carcinoma post-hepatitis C infection in Egyptian patients

AIM To investigate the prospective importance of serum micro(mi)RNAs(mi R-125 b, mi R-138 b, mi R-1269, mi R-214-5p, mi R-494, mi R375 and mi R-145) as early biomarkers for the diagnosis of hepatitis C virus(HCV)-related hepatocellular carcinoma(HCC).METHODS Two-hundred and fifty HCV4 a patients, 224 HCV4 aHCC patients, and 84 healthy controls were enrolled in the study. Expression levels of mi R214-5p, mi R-125 b, mi R-1269 and mi R-375 were quantified using quantitative real-time PCR.RESULTS Expression of the selected mi RNAs in serum wassignificantly lower in HCC patients than in the healthy controls, except for mi R-1269 and mi R-494. There was a significant difference between HCC and HCV patients, in particular for HCC and late stage fibrosis, rather than HCV patients and early fibrosis. It is obvious that mi R-1269 was significantly upregulated in HCC cases compared to hepatic fibrosis cases. Each mi RNA can show HCC progression. Multivariate logistic regression analysis indicated that the tested panel of mi RNAs(mi R214-5p, mi R-125 b, mi R-1269 and mi R-375) represent accurate and specific indictors of HCC development.CONCLUSION This study presents a panel of mi RNAs with strong power as putative diagnostic and prognostic biomarkers for HCV-induced HCC. Moreover, mi R-214-5p and mi R-1269 could be considered as early biomarkers for tracking the progress of liver fibrosis to HCC.

Hepatitis-related hepatocellular carcinoma: Insights into cytokine gene polymorphisms

Hepatocellular carcinoma(HCC) is a primary liver cancer, which is one of the most prevalent cancers among humans. Many factors are involved in the liver carcinogenesis as lifestyle and environmental factors. Hepatitis virus infections are now recognized as the chief etiology of HCC; however, the precise mechanism is still enigmatic till now. The inflammation triggered by the cytokine-mediated immune response, was reported to be the closest factor of HCC development. Cytokines are immunoregulatory proteins produced by immune cells, functioning as orchestrators of the immune response. Genes of cytokines and their receptors are known to be polymorphic, which give rise to variations in their genes. These variations have a great impact on the expression levels of the secreted cytokines. Therefore, cytokine gene polymorphisms are involved in the molecular mechanisms of several diseases. This piece of work aims to shed much light on the role of cytokine gene polymorphisms as genetic host factor in hepatitis related HCC.

MicroRNA signature in patients with hepatocellular carcinoma associated with type 2 diabetes

BACKGROUND Nonalcoholic steatohepatitis-related cirrhosis is one of the liver complications in type 2 diabetes mellitus(T2DM)and reported to be a risk factor for developing hepatocellular carcinoma(HCC).A reliable screening biomarker of liver cirrhosis(LC)and HCC among T2DM patients is important to reduce the morbidity and mortality of this disease.MicroRNA(miRNA)is considered a key player in HCC and T2DM,and it might be a hidden culprit in diabetes-associated HCC,making it a promising reliable prognostic tool.AIM To investigate the signature of serum miRNAs as early biomarkers for the screening of HCC among diabetic patients.METHODS Expression profiles of miRNAs in serum samples of diabetic LC and diabetic HCC patients were assessed using Illumina sequencing;then,RT-qPCR was used to validate significantly altered miRNAs between the two groups.Candidate miRNAs were tested in serum samples of 200 T2DM patients,270 LC patients,200 HCC patients,and 225 healthy control subjects.Additionally,receiver operating characteristic(ROC)analysis,with area under the curve(AUC),was performed to assess the diagnostic performance of the screened miRNAs for discriminating HCC from LC and nonmalignant patients(LC+T2DM).RESULTS Expression of the sequenced miRNAs in serum was different in HCC vs LCpositive T2DM patients.Two miRNAs(miR-34a,miR-221)were significantly upregulated and five miRNAs(miR-16,miR-23-3p,miR-122-5p,miR-198,miR-199a-3p)were significantly down-regulated in HCC compared to LC patients.Analysis of ROC curve demonstrated that the combination of these seven miRNAs can be used as a reliable biomarker for detection of HCC in diabetic patients,as it could identify HCC with high diagnostic accuracy in diabetic LC patients(AUC=0.993)and in diabetic nonmalignant patients(AUC=0.961).CONCLUSION This study validates a panel of serum miRNAs that can be used as a reliable noninvasive screening biomarker of HCC among T2DM cirrhotic and noncirrhotic patients.The study recommends further research to shed light on a possible role of c-Met in T2DM-associated HCC via the miRNA regulatory pathway.

An Update on Efficacy and Safety of Emerging Hepatic Antifibrotic Agents

Liver fibrosis represents a response to chronic liver injury.Metabolic dysfunction-associated fatty liver disease and metabolic dysfunction-associated steatohepatitis are the most common chronic liver diseases,both with increasing incidence.Therefore,there is a great impetus for development of agents targeting these conditions.Accumulating data on possible treatment options for liver fibrosis are emerging in the literature.However,despite extensive research and much effort in the field,approved agents for liver fibrosis are still lacking.In this critical review,we have summarized the main data about specific treatment options for liver fibrosis gained from ongoing clinical trials,with an emphasis on efficacy and safety of these agents.