A Comprehensive Review on Pharmacotherapeutics of Three Phytochemicals,Curcumin, Quercetin,and Allicin,in the Treatment of Gastric Cancer

Objective

Gastric cancer is one of the most common causes of cancer-related death worldwide. Medicinal plants are one of the main sources for discovery of new pharmacological agents especially for treatment of cancers. The aim of the present study is to review pharmacotherapeutic aspects of three mostly studied phytochemicals including curcumin, quercetin, and allicin for management of gastric cancer.

Methods

Scopus, PubMed, Web of Science, and Google Scholar were searched for the effects of curcumin, quercetin, allicin, and their analogs in gastric cancer. Data were collected up to November 2015. The search terms were “curcumin,” “quercetin,” “allicin,” and “gastric cancer” or “cancer.”

Results

Curcumin demonstrated anti-angiogenic, anti-proliferative, anti-metastatic, pro-apoptotic, and anti-helicobacter activities. Quercetin inhibited cell growth and induced apoptosis, necrosis, and autophagy as well as anti-Helicobacter activity. Allicin showed apoptotic and anti-Helicobacter properties. All three natural compounds had low bioavailability.

Conclusions

Although preclinical studies demonstrated the activity of curcumin, quercetin, and allicin in gastric cancer, clinical trials are needed to confirm their effectiveness. Applying their possible synergistic action and suitable drug delivery system in clinical studies can be also an attractive approach with the purpose of finding new extremely efficient anti-gastric cancer agents.

Mini-Abstract

Curcumin, quercetin, and allicin seem to be good candidates for management of gastric cancer through their pro-apoptotic, anti-proliferative, and anti-helicobacter activities.

     

Metabolic iodine and tumours

Purpose

Purpose of the work is to highlight a possible connection between metabolic iodine and natural tumour control.

Method

Method adopted is to use information available in the literature.

Result

Result indicated a means of the purpose being attained.

Conclusion

Conclusion drawn is that a tumour control method derives from the relationship studied.

     

Cancers et environnement : explorer les comportements de recherche et les sources d’information des personnes atteintes et non atteintes d’un cancer

Aim

To explore information-seeking behaviors on links between cancers and environment.

Method

Focus groups and individual semi-structured interviews realized, respectively, with individuals without and with personal cancer experience.

Results

The majority of respondents reported informationscanning behaviors. Only half cancer patients searched for information regarding the links between cancers and environment.

Conclusion

Little information is sought on links between cancers and environment.

     

Carfilzomib demonstrates broad anti-tumor activity in pre-clinical non-small cell and small cell lung cancer models

Background

Carfilzomib (CFZ) is a proteasome inhibitor that selectively and irreversibly binds to its target and has been approved in the US for treatment of relapsed and refractory multiple myeloma. Phase 1B studies of CFZ reported signals of clinical activity in solid tumors, including small cell lung cancer (SCLC). The aim of this study was to investigate the activity of CFZ in lung cancer models.

Methods

A diverse panel of human lung cancer cell lines and a SHP77 small cell lung cancer xenograft model were used to investigate the anti-tumor activity of CFZ.

Results

CFZ treatment inhibited both the constitutive proteasome and the immunoproteasome in lung cancer cell lines. CFZ had marked anti-proliferative activity in A549, H1993, H520, H460, and H1299 non-small cell lung cancer (NSCLC) cell lines, with IC₅₀ values after 96 hour exposure from <1.0 nM to 36 nM. CFZ had more variable effects in the SHP77 and DMS114 SCLC cell lines, with IC₅₀ values at 96 hours from <1 nM to 203 nM. Western blot analysis of CFZ-treated H1993 and SHP77 cells showed cleavage of poly ADP ribose polymerase (PARP) and caspase-3, indicative of apoptosis, and induction of microtubule-associated protein-1 light chain-3B (LC3B), indicative of autophagy. In SHP77 flank xenograft tumors, CFZ monotherapy inhibited tumor growth and prolonged survival, while no additive or synergistic anti-tumor efficacy was observed for CFZ + cisplatin (CDDP).

Conclusions

CFZ demonstrated anti-proliferative activity in lung cancer cell lines in vitro and resulted in a significant survival advantage in mice with SHP77 SCLC xenografts, supporting further pre-clinical and clinical investigations of CFZ in NSCLC and SCLC.

     

Knockdown of OCT4 may sensitize NSCLC cells to cisplatin

Purpose

Cisplatin is commonly used in non-small-cell lung cancer (NSCLC) chemotherapy; however, chemoresistance to cisplatin remains a great clinical challenge. Octamer-binding protein 4 (OCT4) has been reported to be overexpressed in NSCLC. In this study, we aimed to investigate the potential role of OCT4 in NSCLC with chemoresistance to cisplatin.

Methods

Expressions of OCT4 was detected in NSCLC tissues and cell lines. We utilized siRNA to knock down OCT4 expression in human NSCLC cells and analyzed their phenotypic changes.

Results

We found that the difference of OCT4 expression between NSCLC and the adjacent non-tumourous tissues was statistically significant. Knockdown of OCT4 in NSCLC cells could decrease cell proliferation, and potentiate apoptosis induced by cisplatin, suggesting OCT4 may contribute to cisplatin resistance in NSCLC.

Conclusion

Our findings indicate that targeting OCT4 could improve cisplatin effect in NSCLC, confirming their role in modulating cisplatin sensitivity.

     

A risk prediction model to allow personalized screening for cervical cancer

Importance

Cervical cancer screening guidelines are in evolution. Current guidelines do not differentiate recommendations based on individual patient risk.

Objective

To derive and validate a tool for predicting individualized probability of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) at a single time point, based on demographic factors and medical history.

Design

The study design consisted of an observational cohort with hierarchical generalized linear regression modeling.

Setting

The study was conducted in a setting of 33 primary care practices from 2004 to 2010.

Participants

The participants of the study were women aged ≥?30 years.

Main outcome and measures

CIN2+ was the main outcome on biopsy, and the following predictors were included: age, race, marital status, insurance type, smoking history, median income based on zip code, prior human papilloma virus (HPV) results.

Results

The final dataset included 99,319 women. Of these, 745 (0.75%) had CIN2+. The multivariable model had a C-statistic of 0.81. All factors but race were independently associated with CIN2+. The model categorized women as having below-average CIN2+ risk (0.15% predicted vs. 0.12% observed risk), average CIN2+ risk (0.42% predicted vs. 0.36% observed), and above-average CIN2+ risk (1.76% predicted vs. 1.85% observed). Before screening, women at below-average risk had a risk of CIN2+ well below that of women with ASCUS and HPV negative (0.12 vs. 0.20%).

Conclusions and relevance

A multivariable model using data from the electronic health record was able to stratify women across a 50-fold gradient of risk for CIN2+. After further validation, use of a similar model could enable more targeted cervical cancer screening.

     

Preparation of Folic Acid-Targeted Temperature-Sensitive Magnetoliposomes and their Antitumor Effects In Vitro and In Vivo

Background

Ovarian cancer is a common gynecologic malignancy with poor prognosis, requiring innovative new therapeutic strategies. Temperature-controlled drug delivery to cancer cells represents a novel, promising, targeted treatment approach.

Objective

We prepared folate receptor-targeted thermosensitive liposomes wrapped with the HSP90 inhibitor 17-AAG and superparamagnetic material (17-AAG/MTSLs-FA), and tested the efficacy of these targeted magnetoliposomes in vitro and in vivo.

Methods

Magnetic thermosensitive liposomes wrapped with 17-AAG were coprecipitated with Fe₃O₄ magnetic nanoparticles and prepared by a rotary evaporation method. Experiments were conducted with SKOV3 human ovarian cancer cells and MCF7 human breast carcinoma cells to evaluate the anti-tumor effects.

Results

17-AAG/MTSLs-FA prepared in this study met the basic requirements for therapeutic application. The preparation method is relatively simple and the raw materials are readily available. The product exhibited strong magnetism, high encapsulation efficiencies, and satisfactory performance. The liposomes combined with hyperthermia significantly inhibited the proliferation of SKOV3 cells and induced apoptosis. Experiments using a mouse subcutaneous model as well as an ascites tumor xenograft model indicated that 17-AAG/MTSLs-FA was stable in vivo and effectively targeted tumor tissues expressing the folate receptor.

Conclusions

Folic acid-conjugated 17-AAG magnetic thermosensitive liposomes in combination with an alternating magnetic field for heating can achieve a synergistic anti-tumor effect of chemotherapy and heat treatment, potentially offering a new method for ovarian cancer treatment.

     

Les tumeurs endocrines rectocoliques: particularités anatomocliniques et thérapeutiques

Background

Endocrine tumours of the gastro-intestinal tract are rare and predominate in the small intestine and in the appendix, less commonly in the colon and the rectum.

Aim

The aim of this study is to analyze clinical and pathologic features of an endocrine tumour of the colon and the rectum diagnosed in the Department of Pathology (Sousse, Tunisia).

Methods

Five cases were diagnosed between 1992 and 2006 in our hospital unit. The medical records of the affected patients were analyzed. The pathological material was reviewed and the tumours were classified according to 2000 WHO classification.

Results

The study population consisted of 2 male and 3 female patients. Their median age was 55 years. Two poorly differentiated endocrine carcinomas of the colon, and one colic and two rectal well differentiated endocrine carcinoma were identified.

Conclusion

This study illustrates the importance of adequately diagnosing endocrine tumours because their treatment and prognosis are different from those of conventional carcinoma.

     

A prospective study on dietary fat and incidence of prostate cancer (Malmö, Sweden)

Objective

To study the associations between intake of various types of fat and risk of prostate cancer (PCa) in a population-based cohort.

Methods

We have studied 10,564 initially cancer-free men of the Malmö Diet and Cancer cohort, aged 45–73 years. Diet was assessed by a modified diet history method. Cases and clinical characteristics were ascertained via national and regional registry data.

Results

During a mean follow-up of 11.0 years, 817 incidental PCa cases were diagnosed. Out of these, 281 were classified as advanced. There were 202 cases occurring before 65 years of age. After adjustment for age and energy intake, there was no association between intake of any types of fat and risk of PCa, or between fat intake and advanced PCa or PCa occurring in persons aged <65 years. However, we observed positive associations between intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and risk of PCa. After adjustment for multiple confounders, the latter associations were weakened, but the results were otherwise virtually unchanged.

Conclusions

This large study, with high-validity dietary data, does not support an association between intake of total, saturated, or mono-unsaturated fat and PCa risk. The observed associations between EPA/DHA intakes and PCa are difficult to interpret.

     

Supernormal Electro-Oculograms in Patients with Neurofibromatosis Type 1

Purpose

To asses the retinal pigment epithelium (RPE) function measured by EOG testing in patients with neurofibromatosis type 1 (NF-1). Our preliminary EOG results suggested dysfunction of the RPE in individuals with NF-1. In order to confirm our initial results we performed EOG examination on a larger group of NF-1 patients.

Patients

Studies were performed on 36 patients with clinically diagnosed NF-1 and compared to normal healthy controls.

Methods

Standard EOG recordings were performed in accordance with the International Society for Clinical Electrophysiology of Vision (ISCEV) standards.

Results

In NF-1 patients the Arden indexes of the EOG test were significantly higher primarily due to the lower values of dark troughs. Supernormal EOGs (exceeding the value of the mean + 2 SD from the control group) were present in 58% of NF-1 patients.

Conclusions

Dysfunction of the RPE is a characteristic feature of individuals with NF-1.

     

Déplacement,rationalisation et intellectualisation: une évaluation des principaux mécanismes de défense des soignants en oncologie

Aims

This study aims to identify the most used defense mechanisms in oncology clinicians.

Method

Defenses were evaluated conducting an interview with a simulated patient in 62 nurses and 51 physicians by means of the Defense Mechanism Rating Scales for Clinician (DMRS-C).

Results

Displacement (20%), rationalization (19.1%) and intellectualization (12.1%) were the most frequently observed mechanisms.

Conclusion

These results underline the need to include the topic of the stress induced by the interview in clinicians during communication skills training in oncology.

     

Validation of a Liver Index and Its Significance for HCC Aggressiveness

Background

We recently constructed a liver index (LI) from four liver parameters, namely: blood total bilirubin, gamma glutamyl transpeptidase (GGTP), albumin, and platelet levels (a cirrhosis surrogate). We found that the scores for the liver index related significantly to a four-parameter HCC aggressiveness index (maximum tumor diameter, multifocality, percent portal vein invasion, and blood AFP levels).

Aims

To validate the relationship of liver parameters to tumor aggressiveness parameters in a larger, different HCC dataset.

Results

We now confirm these associations in another large HCC cohort. Furthermore, this liver index showed significant trends with the individual HCC aggressiveness parameters.

Conclusions

These results provide further support for the idea that liver microenvironment, as reflected in liver function tests, may relate to HCC behavior.

     

Docosahexaenoic acid reduces sterol regulatory element binding protein-1 and fatty acid synthase expression and inhibits cell proliferation by inhibiting pAkt signaling in a human breast cancer MCF-7 cell line

Background

Fatty acid synthase (FASN), the major enzyme in de novo fatty acid synthesis, is highly expressed in breast cancer and its expression is reduced by polyunsaturated fatty acids (PUFAs) in liver. We previously found a positive association between rat mammary tumor levels of the n-6 PUFA arachidonic acid (AA) and tumor weight. We examined the roles of the major n-3 PUFA, docosahexaenoic acid (DHA, 22:6n-3), and the major n-6 PUFA, AA, in FASN expression in, and proliferation of, human breast cancer MCF-7 cells.

Methods

The cells were treated for 48 h with BSA or 60 μM BSA-bound DHA, AA, or oleic acid (OA, 18:1n-9), then were incubated with or without estradiol or insulin. Western blot and ³H–thymidine incorporation assay were used to determine the role of DHA on FASN regulation and MCF-7 cell proliferation.

Results

DHA, but neither AA nor OA, inhibits estradiol-induced and insulin-induced expression of the precursor of sterol regulatory element binding protein-1 (p-SREBP-1), its mature form (m-SREBP-1), and FASN. Estradiol or insulin stimulation increased the pAkt/Akt and pS6/S6 ratios, expression of p-SREBP-1, m-SREBP-1, and FASN, and cell proliferation, and these effects were decreased by DHA. The DHA-induced decrease in FASN expression resulted from reduced pAkt/Akt signaling and not pERK1/2/ERK1/2 signaling. In addition, DHA enhanced the inhibitory effect of LY294002 on pAkt signaling and expression of p-SREBP-1, m-SREBP-1, and FASN. However, addition of rapamycin, an inhibitor of the mTOR signaling pathways, 1 h before addition of estradiol or insulin increased the pAkt/Akt ratio and FASN expression, and this effect was inhibited by addition of DHA 48 h before rapamycin.

Conclusion

We conclude that, in MCF-7 cells, DHA inhibits pAKT signaling and thus expression of p-SREBP-1, m-SREBP-1, and FASN and cell proliferation.

     

Use of diode laser in oral submucous fibrosis with trismus: prospective clinical study

Introduction

Oral submucous fibrosis (OSMF) in later stages invariably leads to trismus due to retromolar fibrosis and buccal mucosa involvement. Medical treatment has limited role once trismus is established. Various surgical methods have been used with varying success to relieve trismus. We used diode laser to relieve trismus. All patients were diagnosed to have OSMF with trismus. The results are quite encouraging.

Study design

Prospective clinical study. This study involved 8 patients between the years 2002 and 2006.

Objective

To evaluate the efficacy of laser to reduce trismus in OSMF

Methods

Laser with follow-up physiotherapy

Conclusion

Diode laser gave good result in all our patients. Diode laser is a less expensive and alternative method in group III and group IVA cases in whom bilateral temporalis myotomy and coronoidectomy are considered to be the only solution.This technique has less morbidity and is suitable for Asian population as it requires less hospital stay and less followup as compared to other surgical methods.

     

Treatment of LS174T colorectal cancer stem-like cells with n-3 PUFAs induces growth suppression through inhibition of survivin expression and induction of caspase-3 activation

Purpose

Colorectal cancer stem cells (CCSCs) are thought to contribute to tumor initiation, progression, metastasis, chemo-resistance and therapy failure. Therefore, assessment of the effectiveness of agents with anti-proliferative activities against CCSCs is warranted. Several studies have shown that different tumorigenic steps, ranging from initiation to metastasis, can be affected by n-3 polyunsaturated fatty acids (PUFAs). Here, we evaluated the effects of the PUFA components docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), alone or in combination, on LS174T cells that serve as a model for colorectal cancer initiating cells with stem cell-like properties.

Methods

LS174T cells were treated with 50, 100 and 150 μM DHA and EPA, or equal mixtures of DHA/EPA (i.e., 25/25, 50/50 and 75/75 μM), after which cell number, viability, growth inhibition, survivin expression, caspase-3 activation and apoptotic rate were evaluated.

Results

We found that treatment of LS174T cells with increasing PUFA concentrations significantly increased growth inhibition in a dose- and time-dependent manner. After a 72 h treatment with 150 μM DHA and EPA, or their combination (75/75 μM), growth rates were inhibited by 80.3?±?5.5 %, 79.3?±?5 % and 71.1?±?1 %, respectively, compared to untreated cells. We also found that treatment for 48 h with 100 μM DHA and EPA, or their combination (50/50 μM), resulted in 2.9-, 3- and 2.6-fold increases in caspase-3 activation, as well as 54, 62.4 and 100 % decreases in survivin mRNA expression levels, respectively, compared to untreated cells. Low survivin mRNA levels combined with high caspase-3 activity levels were found to correlate with a higher growth inhibition in PUFA-treated cells. DHA appears to be a more potent growth inhibitor than EPA and the DHA/EPA combination. An increase in the number of apoptotic cells (early?+?late), ranging from 12.9 to 44.7 %, was observed with increasing DHA doses.

Conclusion

From our data we conclude that PUFAs induce growth inhibition via targeting survivin expression in LS174T cells, which serve as a model for CCSCs.

     

Descending thoracic aortic aneurysm revealing metastasis of a soft tissue fibrosarcoma: a case report and review of the literature

Background

Review of the first documented case of aortic wall metastasis from a limb sarcoma.

Case presentation

In a 56-year-old woman with a diagnosis of a high-grade limb fibrosarcoma, an aortic metastasis was revealed by a fast growing aneurysm of the descending thoracic aorta. This was managed with an endoprosthesis.

Conclusion

The presence of an aneurysm in a patient with a sarcoma with a high potential for metastasis and poor cardiovascular risk factors should alert physicians.

     

A prospective study of autoantibodies to Ezrin and pancreatic cancer risk

Purpose

No biomarker is available for pancreatic cancer early detection, but a small prospective European study involving 16 cases and 32 controls raised the possibility that anti-Ezrin autoantibodies may be associated with risk of pancreatic cancer. We aimed to validate this finding in a case–control study nested within a prospective study in the USA.

Methods

Levels of anti-Ezrin autoantibodies were examined using ELISA in pre-diagnostic plasma samples of 73 cases and 145 matched controls. Paired t test and paired signed rank tests were used to determine the difference between two groups, and conditional logistic regression was used to evaluate the association between anti-Ezrin autoantibody levels and risk of developing pancreatic cancer.

Results

No association was found between levels of anti-Ezrin plasma autoantibodies and subsequent risk of developing pancreatic cancer.

Conclusion

Anti-Ezrin autoantibodies did not appear to be useful as a plasma biomarker for early detection of pancreatic cancer.

     

Anticancer effects of synthetic hexahydrobenzo [g]chromen-4-one derivatives on human breast cancer cell lines

Background

Cancer results from a series of molecular changes that alter the normal function of cells. Breast cancer is the second leading cause of cancer death in women. To develop novel anticancer agents, new series of chromen derivatives were synthesized and evaluated for their cytotoxic activity against human breast cancer cell lines.

Method

The growth inhibitory activities of synthesized hexahydrobenzo chromen-4-one were screened against six human cancer cell lines using an in vitro cell culture system (MTT assay). Fluorochrome staining (acridine orange/ethidium bromide double staining) and DNA fragmentation by the diphenylamine method were used to investigate the effects of most potent compounds on the process of apoptosis in breast cancer cell lines. To determine the mechanism of apoptosis, ROS and NOX production in treated breast cancer cells with compounds was evaluated.

Results

The cytotoxicity data of tested compounds demonstrate these compounds had varying degree of toxicity. Compound 7h was the most potent compound with IC₅₀ = 1.8 ± 0.6 µg/mL against T-47D cell line. Analyses of the compounds treated (MCF-7, MDA-MB-231, and T-47D) cells by acridine orange/ethidium bromide double staining and DNA fragmentation by the diphenylamine method showed that the synthetic compounds induce apoptosis in the cells. A significant increase in ROS production was observed in T-47D cells treated with IC₅₀ value of compound 7g. Incubation with IC₅₀ value of synthetic compounds increased the NOX production in cell lines, especially T-47D cells.

Conclusion

Our results show that most compounds have a significant anti-proliferative activity against six human cancer cell lines. The observations confirm that chromen derivatives have induced the cell death through apoptosis.

     

Exercise adherence in a randomized trial of exercise on aromatase inhibitor arthralgias in breast cancer survivors: the Hormones and Physical Exercise (HOPE) study

Purpose

Up to 50 % of postmenopausal breast cancer survivors taking aromatase inhibitors (AIs) experience AI-associated arthralgias, or joint pain, which causes many to stop taking AIs and may inhibit exercise, despite known health benefits. We thus evaluated exercise adherence and factors associated with better exercise adherence in breast cancer survivors experiencing AI-induced arthralgia in the (HOPE) year long randomized controlled trial.

Methods

We included 61 HOPE women randomized to exercise (150 min/week of moderate-intensity aerobic exercise and twice-weekly supervised strength training). Our main outcomes were aerobic exercise measured with daily activity logs, attendance at supervised exercise sessions, and changes in cardiorespiratory fitness, measured maximal oxygen consumption (VO₂max). We examined means and standard deviations (SDs) for exercise adherence by demographic and medical characteristics and used the t test for mean differences. We also examined predictors of adherence using linear regression.

Results

On average, at the end of the year long trial, women reported 119 (SD 78)?min/week of moderate-intensity aerobic exercise and participated in 70 % of supervised exercise training sessions. After adjustment for other factors that influence adherence, at 6 months postrandomization, only baseline VO₂max was associated with higher aerobic exercise levels and at 12 months, only older age predicted better supervised exercise training attendance.

Conclusions

Breast cancer survivors taking AIs and experiencing arthralgia are able to initiate and maintain a year long exercise program, regardless of other factors that influence activity levels.

Implications for Cancer Survivors

Breast cancer survivors can exercise at levels that have been shown to improve AI-associated arthralgia.