புற்றுநோய் அறிவியல் & சிகிச்சை

Background: CD24 is a glycosylphosphatidylinositol-linked protein that functions as an adhesion molecule and is overexpressed at an early stage of CRC. The Wnt/β-catenin signaling pathway plays an important role in the CRC carcinogenesis process. We have previously shown that CD24 could affect the tumorigenesis process in ApcMin/+ mice.
Methods: CD24-inducible 293T-RExTM cells previously developed in our lab, HT29 and SW480 CRC cells were used to study this interaction in vitro. ApcMin/+ and CD24 knockout (KO) mice, both on a C57BL/6J genetic background, were crossed to generate double KO transgenic mice. Large bowel polyps were counted macroscopically and small bowel polyps were verified microscopically.
Results: In vitro Western blotting analyses showed that induced expression of CD24 led to the activation of β-catenin. Co-immunoprecipitation studies of CD24 and β-catenin indicated that these two proteins might be interacting. Cytoplasmic/nuclear fractionation showed that more active β-catenin enters the nucleus in cells that express CD24 compared to control cells. In addition, TOP/FOP luciferase reporter assay showed a significant increase in luciferase activity upon CD24 expression induction.Conversely, down-regulation of CD24 by mAbs and siRNA caused a decrease in the levels of active β-catenin. Depletion of CD24 alleles in ApcMin/+ mice led to a significant reduction in the number of polyps in the small and large intestine. The ApcMin/+mice displayed severe splenomegaly compared to ApcMin/+/CD24+/- mice and double KO mice were similar to WT mice with normal spleen size. HGB and RBC levels were significantly lower than in the double KO mice.
Conclusions: CD24 plays a major role in intestinal tumorigenesis. It interacts with the Wnt pathway by activating β-catenin. Down regulation of CD24 reduces the polyp burden in mice and therefore it might serve as an important target in the therapy of CRC.

Benign prostatic hyperplasia (BPH) is an age dependent condition that affects old men. The condition is associated with symptoms like frequency in urination, hesistancy, nocturia, weak urine stream and sexual dysfunction. There is thus, need for update of the medications of the disease. Most BPH patients use conventional methods that include drugs targeting 5-alpha reductase enzyme and invasive surgery. These conventional methods lead to severe side effects including erectile dysfunction and gynecomastia. People prefer to go for phytotherapy for the management of the condition to avoid these adverse effects. Finasteride, for example has been found to cause erectile disfunction unlike Serenoa repens whose side effects are infrequent and mild. This review provides information on conventional methods of alleviating the condition as well as phytotherapy options. Alternative medicine alleviate the symptoms of BPH but have less severe or no side effects.

Mitogen activated proteinase kinase (MAPK) is a key regulator of cellular growth and survival. Mutations in the MAPK pathway genes such as EGFR, KRAS, BRAF and PIK3CA lead to cellular disequilibrium that result into overgrowth and different type of carcinoma including colorectal carcinoma (CRC). Different techniques have been used to determine mutations in the above mentioned genes, and frequency of mutations can vary in different population. The aim of our study was to evaluate the frequency of mutations in the hotspot regions of EGFR, KRAS, BRAF and PIK3CA genes in Swedish colon carcinoma patients by pyrosequencing, and to correlate with different clinicopathological parameters and patient survival. We screened 124 colon cancer patients by using pyrosequencing. We detected Kras, Braf and PIK3CA mutations in 24%, 18.5% and 5.6% of the patients respectively while no mutation was observed for EGFR in our cohort. Kras mutations significantly correlated with lymph node metastasis and advanced UICC stages and poor patient survival (HR; 2.26, 95% CI; 1.273-4.13, log rank P, 0.006). Non-significant correlations were observed between Braf and all parameters including patient survival except with right sided colon cancer. PIK3CA mutations were associated with lymph node metastasis, distant metastasis and higher UICC stages. Combined mutations in Kras, Braf and PIK3CA were significantly associated with lymph node metastasis and colon cancer located on the right flexure. PIK3CA and Kras co-mutations were observed in 4 patients and were significantly associated with lymph node metastasis, distant metastasis and advanced UICC stages.

Cancer is referred to as uncontrolled abnormal proliferation of body cells. Currently cancer treatment and management is a challenge due to complexity of the disease, toxicity of chemotherapy, unaffordability of treatment and severe side effects. Therefore, it is imperative to investigate complementary and alternative medicine for leads and development of anticancer drugs. Cassia abbreviate (C. abbreviata) has been traditionally used for its ethnotherapeutic properties and pharmacological activities. It has been reported to possess antiproliferative activity, though there is no scientific evidence to validate this claim. The main objective of this study was to determine the antiproliferative activity of aqueous root bark extract of C. abbreviata on hepatocellular carcinoma (HCC), vero, and macrophage cell lines in vitro. The antiproliferative activity of aqueous root bark extract of C. abbreviata was determined using MTT assay. The results showed that aqueous root bark extract of C. abbreviata has antiproliferative activity against HCC, vero and macrophage cell lines. The extract had the highest antiproliferative activity against HCC cell line with an IC50 of 1.49 μg/ml as compared to 81.08 μg/ml and 128.38 μg/ml in macrophages and vero cells respectively. The IC50 observed on non-cancerous normal cells (macrophages and vero cells) indicated that the plant extract had little antiproliferative effects on normal cells hence regarded as safe. The extract contained flavonoids, phenols, tannins and saponins. In conclusion the antiproliferative activity of aqueous root bark extract of Cassia abbreviata observed could be attributed to the phytochemicals present in this plant extract. The results of this study, validates the claim that aqueous root bark extract of C. abbreviata has antiproliferative activity and justifies its use in herbal medicine.

1205Lu is a “work horse” melanoma cell line established in our laboratory at the Wistar Institute. It has been used in countless studies since its derivation in 1993. The cell line was generated by sequentially passaging the primary human melanoma cell line WM793 through immune deficient mice and harvesting lung metastases. The lungs from the fifth passage were cultured to establish the permanent cell line 1205Lu. Due to the many requests for melanoma cell lines and in an effort to facilitate distribution of the Wistar Melanoma Cell Lines, Coriell Institute of Medical Research (Camden, NJ) was contracted to grow and distribute our most popular melanoma cell lines including 1205Lu, which was submitted to Coriell in 2008. Before sending each cell line stock to Coriell, we tested for mycoplasma and short tandem repeat (STR) profile using AmpFlSTR® Identifiler® PCR Amplification Kit (Catalog Number 4322288) by Life Technologies