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AbstractPurpose.Chemotherapy has been the historical mainstay of treatment for patients with breast cancer, with immunohistochemical markers and tumor characteristics driving treatment decisions. The discovery of different intrinsic subtypes of breast cancer has advanced the understanding of breast cancer, with gene‐based assays shedding further light on tumor behavior and response to treatment.Design.This review focuses on the landscape of the luminal A subtype, its definition based on immunohistochemistry (IHC) and gene assays, the prognostic and predictive value of these assays, guideline recommendations, and treatment implications.Results.Clinical studies of the prognostic value of gene‐based and IHC‐based assays in patients with luminal A‐subtype breast cancers suggest a better prognosis for these patients compared with those with breast cancers of other subtypes.Conclusion.In today's era of precision medicine, the best treatment regimen for patients with luminal A‐subtype tumors is still undetermined, but available data raise the question whether chemotherapy can be omitted and endocrine therapy alone is sufficient for this patient population.Implications for Practice.Immunohistochemical markers have traditionally guided treatment decisions in breast cancer. However, advances in gene‐expression profiling and availability of gene‐based assays have launched these newer tests into everyday clinical practice. Luminal A‐subtype tumors are a unique subset that may have favorable tumor biology. Properly defining this tumor subtype is important and may identify a subset of patients for whom endocrine therapy alone is sufficient.

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Temozolomide Plus Bevacizumab in Elderly Patients with Newly Diagnosed Glioblastoma and Poor Performance Status: An ANOCEF Phase II Trial (ATAG)

AbstractLessons Learned. Results suggest that the combination of bevacizumab plus temozolomide is active in terms of response rate, survival, performance, quality of life, and cognition in elderly patients with glioblastoma multiforme with poor performance status.Whether this combination is superior to temozolomide alone remains to be demonstrated by a randomized study.Background.The optimal treatment of glioblastoma multiforme (GBM) in patients aged ≥70 years with a Karnofsky performance status (KPS) <70 is not established. This clinical trial evaluated the efficacy and safety of upfront temozolomide (TMZ) and bevacizumab (Bev) in patients aged ≥70 years and a KPS <70.Materials and Methods.Patients aged ≥70 years with a KPS <70 and biopsy‐proven GBM were eligible for this multicenter, prospective, nonrandomized, phase II trial of older patients with impaired performance status. Treatment consisted of TMZ administered at 130–150 mg/m2 per day for 5 days every 4 weeks plus Bev administered at 10 mg/kg every 2 weeks.Results.The trial included 66 patients (median age of 76 years; median KPS of 60). The median overall survival (OS) was 23.9 weeks (95% confidence interval [CI], 19–27.6), and the median progression‐free survival (PFS) was 15.3 weeks (95% CI, 12.9–19.3). Twenty‐two (33%) patients became transiently capable of self‐care (i.e., KPS >70). Cognition and quality of life significantly improved over time during treatment. Grade ≥3 hematological adverse events occurred in 13 (20%) patients, high blood pressure in 16 (24%), venous thromboembolism in 3 (4.5%), cerebral hemorrhage in 2 (3%), and intestinal perforation in 2 (3%).Conclusion.This study suggests that TMZ + Bev treatment is active in elderly patients with GBM with low KPS and has an acceptable tolerance level.

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Cancer Diagnosis: A Trauma for Patients and Doctors Alike

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The emerging use of bioluminescence in medical research

Publication date: May 2018
Source:Biomedicine & Pharmacotherapy, Volume 101
Author(s): Sana Sharifian, Ahmad Homaei, Roohullah Hemmati, Rodney B. Luwor, Khosro Khajeh
Bioluminescence is the light produced by a living organism and is commonly emitted by sea life with Ca²⁺-regulated photoproteins being the most responsible for bioluminescence emission. Marine coelenterates provide important functions involved in essential purposes such as defense, feeding, and breeding. In this review, the main characteristics of marine photoproteins including aequorin, clytin, obelin, berovin, pholasin and symplectin from different marine organisms will be discussed. We will focused on the recent use of recombinant photoproteins in different biomedical research fields including the measurement of Ca²⁺ in different intracellular compartments of animal cells, as labels in the design and development of binding assays. This review will also outline how bioluminescent photoproteins have been used in a plethora of analytical methods including ultra-sensitive assays and in vivo imaging of cellular processes. Due to their unique properties including elective intracellular distribution, wide dynamic range, high signal-to-noise ratio and low Ca²⁺-buffering effect, recombinant photoproteins represent a promising future analytical tool in several in vitro and in vivo experiments.

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The clinical significance and biological function of tropomyosin 4 in colon cancer

Publication date: May 2018
Source:Biomedicine & Pharmacotherapy, Volume 101
Author(s): Rui Yang, Gang Zheng, Defa Ren, Chunzhou Chen, Cheng Zeng, Wei Lu, Hua Li
Tropomyosin 4 (TPM4) has been found to be dys-regulated, and function as oncogene or anti-oncogene in human cancers. However, there was no report on the clinical significance and biological function of TPM4 in colon cancer. This study was designed to investigate the clinical value and biological function of TPM4 in colon cancer. Thus, we detected the TPM4 expression in colon cancer clinical samples, and conducted the gain-of-function in colon cancer cell lines. In our results, TPM4 mRNA and protein expressions were reduced in colon cancer tissues and cell lines compared with normal colon tissues and colon epithelial cell line, respectively. TPM4 protein low-expression was obviously associated with clinical stage, T classification (invasion depth), N classification (lymph node metastasis), distant metastasis and differentiation. Survival analysis showed low-expression of TPM4 was an unfavorable independent prognostic factor for colon cancer patients. Moreover, the experiments in vitro suggested up-regulated TPM4 expression suppressed colon cancer cell migration, invasion and metastasis-associated gene expression including MMP-2, MMP-9 and MT1-MMP, but had no effect on cell proliferation. In conclusion, TPM4 is associated with clinical progression in colon cancer patient and acts as a tumor suppressor in colon cancer cell.

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Kockdown of OIP5-AS1 expression inhibits proliferation, metastasis and EMT progress in hepatoblastoma cells through up-regulating miR-186a-5p and down-regulating ZEB1

Publication date: May 2018
Source:Biomedicine & Pharmacotherapy, Volume 101
Author(s): Ze Zhang, Feng Liu, Fan Yang, Yahui Liu
Long non-coding RNA OIP5-AS1 has been studied in human diseases, including several kinds of cancers. It was not studied or reported in hepatoblastoma, so we chose it to do our research in hepatoblastoma. We thought OIP5-AS1 was oncogenic in hepatoblastoma for the high expression of it in hepatoblastoma tissues and cells. OIP5-AS1 knockdown was carried out in cancer cells. Unsurprisingly, this action was verified to be able to inhibit cell proliferation, metastasis and EMT progress in hepatoblastoma. We then measured the low expression level of miR-186a-5p and the high expression level of ZEB1 in hepatoblastoma tissues and cells. The relevance among them was analyzed by using correlation analysis. In order to prove the ceRNA pattern in this study, nuclear separation experiment, RIP assay and dual luciferase assays were all put into use. We discovered OIP5-AS1 is located in nucleus of cancerous cells. It could target to miR-186a-5p and up-regulate the target gene of miR-186a-5p (ZEB1). Finally, rescue assay was utilized and proved the effect of OIP5-AS1-miR-186a-5p-ZEB1 axis on hepatoblastoma cell activities. Based on all above findings, we came into a conclusion that OIP5-AS1 is a ceRNA in Hepatoblastoma cells through modulating miR-186a-5p/ZEB1.

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The chemistry and pharmacology of Cleome genus: A review

Publication date: May 2018
Source:Biomedicine & Pharmacotherapy, Volume 101
Author(s): Harpreet Singh, Amrita Mishra, Arun Kumar Mishra
BackgroundSince ancient times, species of Cleome genus are used to cure various ailments in human beings and same is stated in traditional treatises. Each part of the plant has its own significance, therefore, in background of its significance, upto date information in systematic manner is required.PurposeThe present review embarks on variety of naturally occurring compounds that have been isolated from various species of Cleome genus. The present study furnishes an overview of all naturally isolated compounds diterpenes, triterpenoids, trinorterpenoids, flavonol glycoside, coumarinolignoids, dipyridodiazepinone, essential oils, sesquiterpenes, flavonoids, carboxylic acid derivatives, lactone derivatives, sterols and pharmacological activities of various species of Cleome genus. These plants of Cleome genus are often used as conventional drugs to treat several ailments therefore information on analgesic, anti-inflammatory, antifungal, antimicrobial, anti-diarrheal, anticancer, anti-arthritic, hepatoprotective, antinociceptive, wound healing and psychopharmacological activity etc were compiled.MethodLiterature regarding the compounds isolated and pharmacological studies performed by various researchers in the last 40 years who worked on different species belonging to genus Cleome was summarized in the present review.ResultsOn the basis of references, this review covers the phytochemistry and pharmacology of Cleome species, describing compounds previously reported current trends and future prospects.ConclusionFrom a wellbeing point of view, species belonging toCleome genus presents an excellent option for curing variety of ailments in human beings due to its isolated phytocompounds that reveal significant biological activities or for developing a variety of new pharmaceutical products.Future PerspectiveThe observed pharmacological activities and no toxicity profile of extracts obtained from species of Cleome genus support the statement that these extracts might be used in the formation of new formulations that can be beneficial to treat various ailments.

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Silymarin and caffeine combination ameliorates experimentally-induced hepatic fibrosis through down-regulation of LPAR1 expression

Publication date: May 2018
Source:Biomedicine & Pharmacotherapy, Volume 101
Author(s): Salma M. Eraky, Mohamed El-Mesery, Amro El-Karef, Laila A. Eissa, Amal M. El-Gayar
AimsLysophosphatidic acid is a lipid mediator that is supposed to be implicated in hepatic fibrosis. Silymarin and caffeine are natural compounds known for their anti-inflammatory and antioxidant effects. Our study aimed to explore the effect of silymarin, caffeine, and their combination on lysophosphatidic acid receptor 1 (LPAR1) pathway in thioacetamide (TAA)-induced hepatic fibrosis.Main methodsHepatic fibrosis was induced in male Sprague-Dawley rats by intraperitoneal injection of 200 mg/kg of TAA twice a week for 8 weeks. Silymarin (50 mg/kg), caffeine (50 mg/kg), and their combination (50 mg/kg silymarin + 50 mg/kg caffeine) were orally given to rats every day for 8 weeks along with TAA injection. Liver functions were measured. Histopathological examination of liver tissues was performed using hematoxylin and eosin and Masson's trichrome staining. mRNA expressions of LPAR1, transforming growth factor beta 1 (TGF-β1), connective tissue growth factor (CTGF), and alpha smooth muscle actin (α-SMA) were measured using RT-PCR. LPAR1 tissue expression was scored using immunohistochemistry.Key findingsSilymarin, caffeine, and their combination significantly improved liver function. They caused significant decrease in fibrosis and necro-inflammatory scores. Combination of silymain and caffeine caused a significant decrease in the necro-inflammatory score than the single treatment with silymarin or caffeine. In addition, silymarin, caffeine, and their combination significantly decreased hepatic LPAR1, TGF-β1, CTGF, and α-SMA gene expressions and LPAR1 tissue expression.SignificanceSilymarin, caffeine, and their combination protect against liver fibrosis through down-regulation of LPAR1, TGF-β1, and CTGF.

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Quercetin and low level laser therapy promote wound healing process in diabetic rats via structural reorganization and modulatory effects on inflammation and oxidative stress

Publication date: May 2018
Source:Biomedicine & Pharmacotherapy, Volume 101
Author(s): Osama M. Ahmed, Tarek Mohamed, Hala Moustafa, Hany Hamdy, Rasha R. Ahmed, Ebtsam Aboud
This study aimed to evaluate the effect of quercetin and the photo-stimulatory effect of low energy 632.8 nm laser irradiation on excisional wound healing in non-diabetic and diabetic rats. Streptozotocin (45 mg/kg body weight) was intraperitoneally applied for diabetes induction. A full-thickness skin wound (2 × 2 cm²) was aseptically created with a scalpel in non-diabetic and diabetic rats on the shaved back of the animals. The wounded non-diabetic and diabetic rats were treated every other day with quercetin by oral gavage at dose 25 mg/kg body weight and/or with low level laser therapy (LLLT) for 14 days. The wound closure percent calculated during the course of the experiment at days 1, 7 and 14 was remarkably increased as a result of treatment of non-diabetic and diabetic wounded rats with quercetin and LLLT; the treatment with both was the most potent. The elevated blood glucose and the lowered serum insulin levels were significantly improved in diabetic wounded rats treated with quercetin and LLLT as compared to the diabetic wounded control. The histological findings indicated that the wounded skin showed a marked increase in collagen fibers which become well oriented in sub-epidermal tissue, intact epidermis and presence of hyperplasia covering well-developed granulation tissue in the wounded rats treated with quercetin and LLLT as compared to the corresponding wounded control. The elevated levels of serum pro-inflammatory cytokines, IL-1β and TNF-α, as well as PGE-2 and LTB-4 were decreased in non-diabetic and diabetic wounded rats with quercetin and LLLT while the lowered level of serum anti-inflammatory cytokine, IL-10, was increased. The augmented oxidative stress represented by increased serum lipid peroxides level was decreased and the serum level of non-enzymatic anti-oxidant glutathione was increased as a result of treatment with quercetin and LLLT. Thus, it can be suggested that the improvements in glycemic state, cytokines involved in inflammation and antioxidant defense system as well as structural reorganization after treatment with quercetin and LLLT may play pivotal roles in promoting the wound healing process. The study also concluded that the treatment with quercetin in association with LLLT was better in improving wound healing in non-diabetic and diabetic rats than the use of either of each.

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Luminal A Breast Cancer and Molecular Assays: A Review

Temozolomide Plus Bevacizumab in Elderly Patients with Newly Diagnosed Glioblastoma and Poor Performance Status: An ANOCEF Phase II Trial (ATAG)

Cancer Diagnosis: A Trauma for Patients and Doctors Alike

The emerging use of bioluminescence in medical research

The clinical significance and biological function of tropomyosin 4 in colon cancer

Graphical abstract

Kockdown of OIP5-AS1 expression inhibits proliferation, metastasis and EMT progress in hepatoblastoma cells through up-regulating miR-186a-5p and down-regulating ZEB1

The chemistry and pharmacology of Cleome genus: A review

Graphical abstract

Silymarin and caffeine combination ameliorates experimentally-induced hepatic fibrosis through down-regulation of LPAR1 expression

Graphical abstract

Quercetin and low level laser therapy promote wound healing process in diabetic rats via structural reorganization and modulatory effects on inflammation and oxidative stress

Graphical abstract

Multifunctional Two-Dimensional Bi<sub>2</sub>Se<sub>3</sub> Nanodiscs for Anti-Inflammatory Therapy of Inflammatory Bowel Diseases

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