Cancer Science & Therapy

Chemotherapy-induced diarrhea (CID) is a common side effect of cancer treatment and can cause significant morbidity and mortality. The experimental procedure included an oral treatment with S. pinnata bark extract prior (100 mg/Kg/day) or after (100 and 200 mg/ kg body wt.) the induction of a rat mucositis model by injecting a single dose of etoposide (i.p) and treated with S. pinnata bark extract (100 and 200 mg/ kg body wt.) for next 72 hrs. Treatment efficacy was determined by changes in the intestinal morphology and biochemical parameters such as intestinal TNF-α, Interleukin-6 (IL-6) and sodium potassium ATPase after 72 hr, with and without intervention. There was a significant increase in the IL-6 and TNF-α levels and a significant decrease in sodium potassium ATPase activities in intestinal tissue after etoposide injection. However, in the post treatment groups (in both 100 and 200 mg), IL-6 and TNF-α levels reverted back to that of normal. In study group, the animals exposed to Pre and post treatment with S. pinnata extract (100 mg/kg body wt), histological studies showed that S. pinnata bark extract intervention was able to restore the normal morphology and intestinal sodium potassium ATPase activity. The results suggest that S. pinnata bark extract has potentials to prevent the toxic effects of etoposide which expedites to mucositis.

Objective: Ovarian cancer is a gynecological malignancy that has a high mortality rate in women due to metastatic progression and recurrence. miRNAs are small, endogenous, noncoding RNAs that function as tumor suppressors or oncogenes in various human cancers by selectively suppressing the expression of target genes. The objective of this study is to investigate the role of miR-203 in ovarian cancer.

Methods: miR-203 was expressed in ovarian cancer SKOV3 and OVCAR3 cells using lentiviral vector and cell proliferation, migration, invasion were examined using MTT, transwell and Matrigel assays, respectively. Tumor growth was examined using Xenograft mouse model.

Results: miR-203 expression was downregulated, whereas expression of its target gene Snai2 (slug) was upregulated in human ovarian serous carcinoma tissue as compared to normal ovaries. In addition, high miR- 203 expression was associated with long-term survival rate of ovarian cancer patients. miR-203 overexpression inhibited cell proliferation, migration, and invasion of SKOV3 and OVCAR3 ovarian cancer cells. Furthermore, miR-203 overexpression inhibited the epithelial to mesenchymal transition (EMT) in ovarian cancer cells. Silencing Snai2 with lentiviral short hairpin (sh) RNA mimics miR-203-mediated inhibition of EMT and tumor cell invasion. Xenografts of miR-203-overexpressing ovarian cancer cells in immunodeficient mice exhibited a significantly reduced tumor growth.

Conclusion: miR-203 functions as a tumor suppressor by down regulating Snai2 in ovarian cancer.

To explore the effectiveness of Raman spectra to diagnose brain cancer glioblastoma multiforme (GBM), we investigated the Raman spectra of single cell from four different GBM cell lines developed from four different patients and analyzed the spectra. The Raman spectra of brain cancer (GBM) cells were similar in all these cell lines. The results indicate that Raman spectra can offer the experimental basis for the cancer diagnosis and treatment.

Many clinical investigations have suggested that statins are useful chemotherapeutics against various cancers, whereas in vitro experiments using cancer cell lines have shown little effect of statins on cell proliferation and survival. Our group previously demonstrated that statins were preferentially cytotoxic against HeLa, mesothelioma, and pancreatic tumor cells under acidic conditions. A serious side effect of anti-cancer drugs used now is the impairment of the immune system. In this study, we examined the effect of simvastatin on the immune cell lines THP-1 and Jurkat in alkaline and acidic media. Our data suggest that simvastatin inhibited proliferation, survival, and cytokine production at an acidic pH in these cells, whereas the inhibitory effect was negligible at an alkaline pH. These results suggest that anti-cancer drugs whose efficacy increases in acidic cancer nests are useful for potent chemotherapeutics against cancer without causing serious damage to the immune cells in blood and normal tissues, whose pH is slightly alkaline, although the functions of immune cells that have infiltrated acidic cancer nests may be attenuated.

Background: Drug Related Problems (DRPs) in cancer chemotherapy can have severe consequences originating from the high toxicity and narrow therapeutic range of anticancer drugs.

Objective: This study was conducted to investigate drug-related problems and factors associated with it in hospitalized cancer patients at Tikur Anbessa Specialized Hospital.

Method: A cross-sectional study was conducted at Tikur Anbessa Specialized Hospital from January to June 2013. A total of 367 study participants were recruited by simple random sampling technique and data were collected by medical chart review using data abstraction format.

Results: Four hundred seventy four drug-related problems were identified in 274 patients among the 367 patients, which gave rise to a prevalence of 74.7%. The most prevalent drug-related problems was adverse drug reaction (45.5%) followed by dosing problem (37.9%). The risk factors for DRPs were number of medications, comorbidity and length of hospital stay.

Conclusion: Drug related problems were common among cancer patients in our set up indicating a need for intervention like involvement of a pharmacist for better therapeutic outcome.

Cyclin L2 (CCNL2) (Acc. No.: NM_030937) was detected as a tumor antigen of esophageal squamous cell carcinoma (SCC) by serological identification of antigens by recombinant cDNA expression cloning (SEREX). Serum anti-CCNL2 antibodies were detected by enzyme-linked immunosorbent assay more frequent in patients with esophageal SCC than in healthy donors (32% and 15%, P<0.01). An AlphaLISA further confirmed the significant difference in serum antibody levels between the patients and healthy donors using a different set of serum specimens. The expression levels of CCNL2 mRNA detected by reverse transcription polymerase chain reaction were higher in esophageal SCC tissues than those detected in adjacent normal esophageal tissues. We then analyzed for biological function by the transient transfection of CCNL2 expression plasmids into ras-NIH3T3 mouse fibroblasts followed by analysis via luciferase assay using p53-responsive reporter plasmids. CCNL2 increased the transactivation ability of p53, which was attenuated by protein kinase C (PKC) inhibitors or a dominant negative PKCa. Thus, it is possible that CCNL2 activates p53 via PKCa activation.

B cell neoplasms comprise >50% of blood cancers. However, many types of B cell malignancies remain incurable. Identification and validation of novel genetic risk factors and oncogenic signaling pathways are imperative for the development of new therapeutic strategies. We and others recently identified TRAF3, a cytoplasmic adaptor protein, as a novel tumor suppressor in B lymphocytes. We found that TRAF3 inactivation results in prolonged survival of mature B cells, which eventually leads to spontaneous development of B lymphomas in mice. Corroborating our findings, TRAF3 deletions and inactivating mutations frequently occur in human B cell chronic lymphocytic leukemia, splenic marginal zone lymphoma, mantle cell lymphoma, multiple myeloma, Waldenström’s macroglobulinemia, and Hodgkin lymphoma. In this context, we have been investigating TRAF3 signaling mechanisms in B cells, and are developing new therapeutic strategies to target TRAF3 downstream signaling pathways in B cell neoplasms. Here we discuss our new translational data that demonstrate the therapeutic potential of targeting TRAF3 downstream signaling pathways in B lymphoma and multiple myeloma.

Background: Although caspase-3 is a key molecule for apoptosis induction, recent evidence has suggested its protumoral role in various human malignancies. The aim of the present study was to investigate the expression of cleaved caspase-3 (the active form of caspase-3) in both clinical samples and cell lines from oral squamous cell carcinomas (OSCCs) and elaborate on its contribution to the protumor role in oral cancer.

Methods: The expression of cleaved caspase-3 was immunohistochemically evaluated in samples from 30 patients with OSCCs. The samples were either from biopsies or surgically-resected specimens with a mix of clinical stages and tumor site origins. The expression of cleaved caspase-3 was further examined in three OSCC cell lines.

Results: In addition to apoptotic cancer cells, all the cases of OSCCs demonstrated a surprisingly positive expression of cleaved caspase-3. A diffuse, cytoplasmic pattern was particularly prominent in in situ carcinoma cells, invasive carcinoma cells, and metastatic cancer cells that lacked apoptotic morphology. On the other hand, non-neoplastic, normal epithelial cells were completely negative for cleaved caspase-3. In all the OSCC cell lines studied, cleaved caspase-3 was expressed in the cytoplasm and nucleus of cancer cells. Flow cytometric analysis also confirmed that the activation level of caspase-3 in non-apoptotic cancer cells was relatively lower than that in apoptotic cancer cells. Moreover, caspase-3 inhibition by caspase-3 specific inhibitor decreased the proliferation of OSCC cells.

Conclusions: Because cleaved caspase-3 is selectively expressed in non-apoptotic OSCC cells and is associated with cell proliferation, these findings implicate caspase-3 signaling in promoting the progression of oral cancer.