Cancer Science & Therapy

Breast cancer is a leading cause of mortality among women, resulting in more than half a million deaths worldwide every year. Although chemotherapeutic drugs remain the main stay of cancer treatment, it is observed that toxicity to normal cells poses a limitation to their therapeutic values. Moreover, the patient recovery rate from advanced breast cancer by chemotherapy is still unacceptably low. Tetrahydroisoqinoline derivatives (THIQs) were reported to act as selective subtype estrogen receptor antagonists/agonists and may serve as potential therapeutic agents for breast cancer. In continuation of previous work we systematically synthesized and characterized the tetrahydroisoquinoline (THIQs) analogs. In-vitro antiproliferative activity of new substituted tetrahydroisoquinoline analogs were evaluated against human ER (+) MCF-7 (breast), ER (−) MDA-MB-231 (breast) and Ishikawa (endometrial) cancer cell lines using the CellTiter-Glo luminescent cell viability assay. The most active compounds obtained in this study were 2b, 2i, and 3 g as demonstrated by their activity (IC₅₀=0.2 μg/mL, 0.08 μg/mL; 0.61 μg/ mL, 0.09 μg/mL; 0.25 μg/mL, 0.11 μg/mL) against MCF-7 and Ishikawa cell lines respectively, in comparison to Tamoxifen activity (IC₅₀=3.99 μg/mL, 7.87 μg/ml). The newly synthesized molecules were docked in the active sites of the ER-α (PDB: 3ERT), ER-β (PDB: 1QKN) and alpha-beta tubulin taxol complex (1JFF) crystal structures to determine the probable binding modes (bioactive conformations) of the active compounds.

The aim of this research is to facilitate the pursuit of improved chemotherapeutic drugs in combination with epigenetic modifiers. Both in vitro studies and a clinical study have described the combinations of DNA methyltransferase inhibitors with irinotecan and histone deacetylase inhibitors with 5-fluorouracil or gemcitabine to enhance their anti-cancer activities. The molecular mechanisms involved in the potentiation of anti-tumor activities were apoptosis regulation, cellular metabolism, DNA topoisomerase-I upregulation, cell-cell adhesion, regulation of transcription (DNA-templated), DNA repair, and the PI3K/AKT signaling pathway. More importantly, the priming effects and long-lasting effects induced by DNA methyltransferase inhibitors, when applied as a pretreatment, sensitized cancer cells to subsequent anti-cancer drug treatments. The combinations of 5-fluorouracil and gemcitabine with histone deacetylase inhibitors (depsipeptide and valproic acid, respectively), increased the expression of major histocompatibility complex class II, which may warrant further investigation for possible accurate biomarkers and therapeutic targets. As valproic acid downregulated histone deacetylase in patients recruited in a clinical phase I/II study, the activity of valproic acid may be associated with the enhanced anti-tumor activity in combination with 5-fluorouracil. This research provides a positive perspective on the combination therapy of anticancer drugs with epigenetic modifiers.

Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors. It is important to detect disease and recurrence at its earlier period. The aim of this study was to evaluate the influence of the C936T polymorphism of the VEGF and Alfa feto-Protein (AFP) on Hepatocellular carcinoma (HCC), Hepatitis C Virus (HCV) and control groups. Also, estimation of serum AFP and correlation with other parameters was studied. In this study was included 75 subjects, 25 patients with HCV, 25 patients with confirmed HCC and 25 healthy volunteers were subjected to abdominal ultrasonography, AFP and VEGF were assessed. The statistical analysis will include the Fisher exact test, T test and the multivariate regression, with significance level P<0.05 (AU). The result has showed that Serum level of AFP was significantly higher in HCC group when compared with control group and There was a nonsignificant increase in serum (AFP) level in the untreated HCV infected group compared to control group and also there was a nonsignificant increase in serum (AFP) activity in the HCC group compared to untreated HCV infected group with a (P value = 0.203). the influence of the C936T polymorphism of the VEGF distribution of the studied groups showing that Positive gene have higher incidence of HCV and HCC infection than Negative gene, when compared to control group. Sensitivity and specificity of markers in diagnosis of HCC were 52% and 40% respectively for AFP using a cutoff value of 3.39 ng/ml. VEGF may be useful marker for detection of HCC in addition to traditional markers.

Background: Cervical cancer is the most common and leading cause of deaths due to cancer among women in Kenya. Early detection is necessary for initiation of treatments to prevent deaths. Identification of factors that contribute to advanced stage of cervical cancer is the first step towards early detection. Objectives: To determine socio-demographic factors associated with advanced stage of cervical cancer at diagnosis in Kenyatta National Hospital. Materials and methods:A cross-sectional study of 152 women with a histological proven cervical cancer was conducted at Kenyatta National Hospital. The women were selected using random sampling method. Information on demographic characteristics and stage of cervical cancer were abstracted retrospectively by auditing patients’ records from January 2014 to June 2014. Stages I and II were classified as ‘early stage’ and stages III and IV as ‘advanced stage’. Chi-square test (p-value<0.05) was used to determine association between advanced stage of cervical cancer and socio-demographic characteristics. Multiple logistic regression analysis was performed to determine the independent factors associated with advanced stage of cervical cancer at diagnosis. Results: Out of 152 patients with cervical cancer, 53.9% had advanced stage of cancer at diagnosis. Following multiple logistic regression analysis, the following factors were independently associated with advanced stage of cervical cancer: older age (50 to 75 years) (AOR=4.25; 95% CI=1.08-16.75; P=0.039), being single (AOR=2.28; 95% CI=1.03-5.06; P=0.043), never attended school (AOR=5.91; 95% CI=1.96-17.78; P=0.002), attended primary school (AOR=4.13; 95% CI=1.60-10.63; P=0.003) and HIV positive women (AOR=2.86; 95% CI=1.25-6.59; P=0.013). Conclusion:More than half of the patients presented with advanced stage of cervical cancer at diagnosis. None/low level of education, old age, being single and HIV infection were associated with advanced stage of cancer at diagnosis. Regular cervical cancer screening targeting these women could reduce advanced stage of cervical cancer at diagnosis.

Background: Primary giant cell tumor (GCT) of soft tissue (GCTST) is an extremely rare slow-growing entity bearing a high similarity to conventional bone TCG (GCTB). The term, malignant tumor of giant cells of soft tissues have been reserved for histologically high-grade lesions. Although the gold standard remains surgical carcinological resection, bisphosphonates are beginning to prove their benefit in the treatment of GCTST.

Results and Discussion: A 37-year-old man came to the outpatient department of medical oncology with a painful swelling arising from his right elbow. Magnetic resonance imaging (MRI) of the right elbow was done and revealed a 19 cm × 7 cm, T1 and T2 hypointense lesion with significant postcontrast enhancement of calcified tissue nodules, distance extension report was negative. An echo-guided biopsy of the right elbow was performed. The anatomopathological examination showed a poorly delimited encapsulated tumor proliferation composed of sheets of histiocytic cells admixed with multinucleated giant cells dispersed uniformly among this tumor. Cells were embedded in a richly vascularized tissue. No significant nuclear pleomorphism or mitotic activity was appreciated. There were focal areas of osseous metaplasia. On the basis of these date, the diagnosis of giant cell tumor of low malignant potential was retained. Due to its intra-articular extension, the mass was judged unresecable. The case was discussed in a multidisciplinary consultation meeting indicating medical treatment with zoledronic acid given the unavailability of denosumab. After 8 monthly injections of zoledronic acid, a control imaging of the right elbow and forearm concluded to tumor stability.

Conclusion: GCTST is a slow-growing tumor known as soft tissue tumor. Numerous studies show the role of bisphosphonates when complete surgical excision cannot be performed. Further studies are needed to establish a standardized treatment protocol particularly in the context of inoperable large primary GCTST.