कैंसर विज्ञान एवं चिकित्सा

Background: The occurrence of breast Cancer is a rising concern in Bangladesh. A hospital based case control study was conducted.

Methodology: A nationwide representative sample of 100 out of 115 cancer patients aged 20 or older was interviewed at NICRH to provide information on awareness of the risk factors of breast cancer causes in Bangladeshi population.

Results and discussion: Highest number of patients was from 40-49 (39%) and 30-39 (27%) year-age group. About 15% patients had direct family history, 21% had early periods. About 14% have got late menopause. If women begin menopause after age 55, the risk increases. 15% women have had not had children, and 10% had their first child after age 30. Study found women using birth control pills (47%), have slightly greater risk. 9% women’s breast feeding lasts below 1 year. And about 7% patient never breast fed their child. About 40% female patients do not walk as exercise.

Conclusion: Results suggested a mixture of different factors with Aging and direct family history poses higher risk for breast cancer.

Study background: Studies on p-glycoprotein was carried out world vide with cell lines like Caco2, MDR1- LLC-PK1 and MDR1-MDCK in-vitro, but most of the results were failed to produce similar results in-vivo. In the present study curcumin inhibitory action on p-glycoprotein increased permeability of irinotecan, so in the colon cancer it would be beneficial if curcumin used as add on therapy.

Methods: Intra-rectal administered of N-Nitroso N-methyl urea (2 mg/Kg) induced colon cancer. Single pass whole length of colon in-situ perfusion was carried out in rats with irinotecan to study the influence of p-glycoprotein modulators like verapamil and curcumin. The rats were divided in to 5 groups (n=6), Group I served as control perfused with 30 μg/ml of irinotecan, propronolol and phenol red. Group II was cancerous group, induced by N-methyl N-nitroso urea. Group III was perfused with irinotican in cancerous rats. Group IV, perfused with irinotican in presence of verapamil and group V was pre-treated with curcumin and then perfused with irinotican and was estimated by HPLC-UV to effective permeability coefficient.

Results: Our qRT-PCR and Western blot results confirmed that about 15-fold decreases in the expression of p-glycoprotein (P-gp) in curcumin treated colon cancer cells. Irinotecan was increased to 0.00066 cm/s and about 11-fold increase in verapamil-coperfused group, where curcumin pre-treated group irinotecan was increases 0.00006 cm/s to 0.00042 cm/s that is about 7-fold increase p-glycoprotein inhibitory activity by verapamil and curcumin found to be significantly enhanced the cancerous colon permeability of irinotecan.

Conclusions: Any safe suitable p-glycoprotein inhibitors along with irinotecan will enhance the therapeutic benefit in the treatment of the colon cancer.

Most lung cancer patients are diagnosed at an advanced stage, when prognosis is poor. Multidrug resistance and tumor recurrence have been major reasons for these patients to succumb to the disease. Recent evidence points to cancer stem cells as being responsible for multidrug resistance and tumor repopulation as a result of their increased drug efflux and other stem cell-like properties. Thus, recent efforts have focused on targeting these cancer stem cells. Here, we combined liposomal nanoparticles targeted with a legumain inhibitor as a safe vehicle for drug delivery to the tumor microenvironment with Doxorubicin, a common chemotherapeutic agent that targets bulk cancer cells, and IMD-0354, an inhibitor of NF-κB targeting cancer stem cells. IMD-0354 decreased side populations, ABC transporters, stem-like and apoptosis resistance genes, and colony formation of human non-small cell lung cancer cells. In addition, IMD-0354 also had a cytotoxic effect on non-cancer stem cells and increased their apoptosis. The targeted delivery method, used previously in syngeneic mouse models enhanced drug delivery under hypoxia, a hallmark of the tumor microenvironment, but not under normoxia. Further, such targeted delivery reduced in vivo tumor burden in an aggressive model of human non-small cell lung cancer xenografts. Targeting of both bulk tumor cells and cancer stem cells with IMD-0354 as an adjuvant for chemotherapy are likely to reduce multidrug resistance and tumor recurrence, and thereby significantly reduce patient death from non-small cell lung cancer.

Leinamycin is a thiol dependent DNA alkylating agent which shows very potent activity against various human cancer cell lines (IC₅₀ values in the low nanomolar range). This natural compound forms guanine adducts (N7) in DNA which are converted into abasic sites and simultaneously generates Reactive Oxygen Species (ROS), to produce DNA strand breaks in human cancer cells. Our present study shows that leinamycin induces a group of DNA repair and transcription factor genes involved in DNA repair in a MDA-MB-231 human breast cancer cell line, which can mediate chemoresistance to leinamycin. In addition, N-acetylcysteine decreases leinamycin-mediated ROS production while increasing leinamycin mediated apoptotic cell death, without affecting the induction of repair genes. These data indicate that ROS is not a crucial player in leinamycin induced DNA damage and that a precursor of glutathione, N-acetylcysteine, can potentiate leinamycin mediated cytotoxicity by increasing the activation of leinamycin into its DNA reactive form

Most cancer therapies have their main mechanism of action DNA damage. Tumor cells have several ways to respond to this DNA damage: removal of the damaged area and reconstruction of the strand of DNA, activation of DNA damage checkpoint, changes in transcription profile of benefit to the cell and apoptosis in the case in which the DNA is seriously damaged. We summarize in this article the most important cellular responses to DNA damage caused by chemotherapy.

Bcl-2 family, other than in the follicular B-cell lymphoma, is involved in a number of cancers, including melanoma and breast carcinoma, prostate and lung. Its expression was associated with good prognosis in non-small-cell lung cancer. Cytotoxicity of many chemotherapeutic agents is induced through the Bcl-2 apoptotic pathway; overexpression of BCL2 is associated with increased resistance to these agents.

In the search for ways of sensitizing tumor cells to chemotherapy or radiotherapy, the inhibition of DNA repair has recently been proposed as a target of clinical interest. Ionizing radiation, as well as several antitumor drugs, induce the formation of DNA double-strand breaks (DSBs), that are highly damaging to the DNA, leading to cell death and genomic instability. DSBs are mainly repaired by the Non-Homologous End-Joining (NHEJ) process, in which DNA dependent protein kinase (DNA-PK) is the key complex. Consequently, specific DNA-PK inhibitors have been selected and evaluated for sensitizing cells to chemotherapy or radiotherapy. The choice of DNA-PK as a pharmacological target of interest in cancer treatment is discussed.