Clinical Cancer Drugs - Volume 6, Issue 1, 2019

Breast cancer stem cells (BCSCs) are a small proportion of cells that may be responsible for improving the resistance of cancer cells to the treatment and metastasis of breast cancer (MBC). Nanovehicles such as liposomes are extensively explored for diagnosis, treatment, and imaging of cancer. Targeted therapy with nanoparticles can be used to overcome the chemoresistance problem of cancer stem cells. Liposomes are lipid bilayer nanocarriers that have the ability to inhibit Pglycoprotein to overcome multidrug resistance that makes liposome ideal choice for using in BCSCs therapy. The main objective of this review is to describe novel liposomal formulations that are used in targeting BCSCs, which help in improving breast cancer treatment.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancerrelated deaths and its morbidity and mortality are increasing. PDAC patients have a very poor prognosis because of aggressive features of PDAC cells, shortage of reliable diagnostic biomarkers and deficiency of effective therapeutics. Objective: The article aims to discuss the recent progress in the discovery of novel molecular targets and their related mechanisms in the invasion and metastasis of PDAC cells. Methods: Literatures based on Pubmed database were searched and those related to the molecular targets involved in the invasion and metastasis of PDAC were reviewed. Results: The most promising discovery of molecular targets and phenomena include epithelialmesenchymal transition (EMT), cancer stem cells (CSCs), metastasis-related genes, hypoxiainducible factors (HIFs), non-coding RNAs (ncRNAs) and L1 cell adhesion molecule (L1CAM), which contribute to the vital biological behaviors of PDAC cells and tumor microenvironments. Conclusion: This review summarizes recent advances in novel molecular targets that regulate the invasion and metastasis of PDAC cells, and how they are targeted for developing diagnostic and therapeutic tools for combating PDAC. Further understanding the regulatory mechanisms of these molecular targets may help to discover biomarkers used for early diagnosis, predicting the prognosis and monitoring treatment response, and also to develop novel effective therapeutics.

Background: Mammary gland tissue (left half) revealed the presence of excess proliferation of fibrous tissue with disorganization of alveolar structures and the right half showed extensive fibrous tissue proliferation of mammary gland following intramammary inoculation of 2000 c.f.u. of Staphylococcus aureus. However, oral dosing of Bauhinia variegata L. bark powder at 6 gm/kg for 7 days and 3 gm/kg for another 7 days exhibited reduction of fibrous tissue in chronic mastitis. Objective: The fibrolytic effect of one week oral dosing of Bauhinia purpurea L. bark powder was studied in chronic mastitis with induced fibrosis as Bauhinia variegate L. is rarely available in plain land. Methods: Chronic mastitis with fibrosis was induced by intramammary inoculation of coagulase positive Staphylococcus aureus in group III and IV goats. Group I and III goats were injected with a single dose of ceftriaxone at 20 mg/kg intravenously, whereas group II and IV goats were orally administered Bauhinia purpurea L. bark powder at 6 g/kg for 7 days with a single dose of ceftriaxone at 20 mg/kg intravenously. Results: The t1/2β of ceftriaxone with Bauhinia purpurea L. stem bark powder in chronic mastitis increased significantly. Ceftizoxime was detected in plasma from 1 h to 48 h post dosing (pd) in group III and from 1 h to 96 h pd in group IV, respectively. Conclusion: Bark powder of Bauhinia purpurea L. at 6g/kg orally once daily increased the bioavailability of ceftriaxone and or ceftizoxime in milk due to its fibrolytic effect which was not reported earlier. Therefore, the Bauhinia purpurea L. bark powder having fibrolytic effect has the potential to reduce development of cancer.

Background: Cyclin-dependent kinases play a central role in the control of cell division and therefore it is not surprising that cancer exhibits some features that disturb the normal controls over the cell cycle. Previous studies related to the development of 3-Pyrimidinylazaindole (Meriolin) derivatives as novel Cyclin dependent kinase inhibitors highlighted 4ab as the most potent inhibitor. Objective: The main objective of the current study was to understand the mode of cell death and the effect of 4ab on major cellular networking pathways in cancer. Methods: Preliminary apoptotic studies were carried out using flowcytometer and electron microscope. The effect on cellular signalling was studied via western blotting. Results: 4ab was found to inhibit the enzymatic activity of CDK2. The inhibition of CDK2 activity was found to be associated with the down-regulation of P-cdc-25 and arrest of cells in G0-G1 phase of the cell cycle in lymphoblastic leukemia cells. Further, 4ab was found to affect AKT-mToR pathway by down-regulating the expression of major proteins including P-m-TOR (2448), P110α, P-AKT (S473) and P-p-70S6K. Conclusion: Current study shows that the potent anticancer potential of 4ab is mediated via cellular apoptosis, dysregulation of mitochondrial membrane potential and arrest of G1 phase in Molt-4 cells. Further, target-based studies showed the effect of 4ab on one of the major cellular signalling pathways deregulated in cancer.

Background: Cisplatin is an anticancer drug used in the management of solid tumors, however, dose-related nephrotoxicity is one of its major problems. Agents having antioxidants, antiinflammatory and/or antiapoptotic activities may thus represent potential therapeutic options to avoid cisplatin-induced nephrotoxicity. Among these agents, coenzyme Q10 has several pharmacological properties including antioxidant, anti-inflammatory and/or anti-apoptotic effects. Objective: The current study aimed to examine whether coenzyme Q10 could attenuate cisplatininduced nephrotoxicity or not. Methods: 24 adult rats were randomly separated into three groups (8 rats per group). The first one was the control group, rats receiving vehicle (olive oil) intraperitoneally. The second group was Cisplatin treated group, rats were receiving 13 mg/kg of Cisplatin intraperitoneally as a single dose. The third group (Cisplatin + Coenzyme Q10), rats were receiving 13 mg/kg as a single intraperitoneal dose of Cisplatin and coenzyme Q10 daily for six consecutive days (10 mg/kg intraperitoneally). Results: Cisplatin caused significant increases in serum creatinine and severe histological lesions. Cisplatin treated group also showed a significant elevation in renal malondialdehyde concentration as a marker of oxidative stress; renal tumor necrosis factor-alpha concentration as a marker of inflammation; and Kidney injury molecule -1 concentration. Coenzyme Q10 significantly attenuated cisplatininduced nephrotoxicity through lowering serum creatinine and improving nephrotoxicity histological scores. Coenzyme Q10 also significantly reduced the renal concentration of MDA, TNF-α and KIM-1 relative to cisplatin treated group. Conclusions: Coenzyme Q10 has a potential nephroprotective effect against cisplatin-induced nephrotoxicity that was demonstrated by biochemical and histopathological analysis.

Background: Head and neck cancer has predilection of metastasising to the lung, bones or liver. The site of metastasis usually depends on the primary tumour location, the staging and the regional spread of the tumour. Patients with distant metastasis are predicted to have a poor prognosis with low survival rate. Oligometastasis is the term used for an intermediate biologic state of restricted metastatic capacity with limited number and sites of organ with metastasis. It is also defined by 5 or less than 5 metastatic lesion in a disease with a controlled primary tumour. Case reports: In this case series, we have reported three cases of head and neck carcinomas that pose treatment dilemmas because of lung metastases. First case is a gentleman with laryngeal carcinoma with multiple small lung metastases where the treatment options of surgery versus chemoradiation was debated. The second case is a gentleman with low grade mucoepidermoid carcinoma of the parotid gland with suspicious lung spread of disease. Lastly is a patient with papillary thyroid carcinoma with florid lung metastases who completed chemoradiation. Conclusion: The presence of lung metastases does not necessarily mean that the prospect of surviving is poor for the patient. It is necessary to determine the best choice of treatment yielding the best quality of life to maximize the survival period for these patients.