Treatment of cancer with cryochemotherapy

Cryosurgery employs freezing to destroy solid tumours. However, frozen cells can survive and cause cancer recurrence. Bleomycin, an anticancer drug with a huge intrinsic cytotoxicity is normally not very effective because it is nonpermeant. We report that freezing facilitates bleomycin penetration into cells making it toxic to cryosurgery surviving cells at concentrations that are non-toxic systemically

Dual mechanism of daunorubicin-induced cell death in both sensitive and MDR-resistant HL-60 cells

Exposure of some acute myeloid leukaemia (AML) cells to daunorubicin leads to rapid cell death, whereas other AML cells show natural drug resistance. This has been attributed to expression of functional P-glycoprotein resulting in reduced drug accumulation. However, it has also been proposed that P-glycoprotein-expressing multidrug-resistant (MDR) cells are inherently defective for apoptosis. To distinguish between these different possibilities, we have compared the cell death process in a human AML cell line (HL-60) with a MDR subline (HL-60/Vinc) at doses that yield either similar intracellular daunorubicin concentrations or comparable cytotoxicity. Adjustment of the dose to obtain the same intracellular drug accumulation in the two cell lines did not result in equal cytotoxicity, suggesting the presence of additional resistance mechanisms in the P-glycoprotein-expressing HL-60/Vinc cells. However, at equitoxic doses, similar cell death pathways were observed. In HL-60 cells, daunorubicin induced rapid apoptosis at 0.5–1 μM and delayed mitotic cell death at 0.1 μM. These concentrations are within the clinical dose range. Similarly, HL-60/Vinc cells underwent apoptosis at 50–100 μM daunorubicin and mitotic cell death at 10 μM. These results show, for the first time, that anthracyclines can induce cell death by a dual mechanism in both sensitive and MDR cells. Our results also show that not only the cytotoxicity, but also the kinetics and mechanism of cell death, are dose dependent. Interestingly, regrowth was observed only in association with delayed cell death and the formation of enlarged, often polyploid, cells with micronucleation, suggesting that morphological criteria may be useful to evaluate treatment efficacy in patients with myeloid leukaemias. © 1999 Cancer Research Campaig

A Mitosis Block Links Active Cell Cycle with Human Epidermal Differentiation and Results in Endoreplication

How human self-renewal tissues co-ordinate proliferation with differentiation is unclear. Human epidermis undergoes continuous cell growth and differentiation and is permanently exposed to mutagenic hazard. Keratinocytes are thought to arrest cell growth and cell cycle prior to terminal differentiation. However, a growing body of evidence does not satisfy this model. For instance, it does not explain how skin maintains tissue structure in hyperproliferative benign lesions. We have developed and applied novel cell cycle techniques to human skin in situ and determined the dynamics of key cell cycle regulators of DNA replication or mitosis, such as cyclins E, A and B, or members of the anaphase promoting complex pathway: cdc14A, Ndc80/Hec1 and Aurora kinase B. The results show that actively cycling keratinocytes initiate terminal differentiation, arrest in mitosis, continue DNA replication in a special G2/M state, and become polyploid by mitotic slippage. They unambiguously demonstrate that cell cycle progression coexists with terminal differentiation, thus explaining how differentiating cells increase in size. Epidermal differentiating cells arrest in mitosis and a genotoxic-induced mitosis block rapidly pushes epidermal basal cells into differentiation and polyploidy. These observations unravel a novel mitosis-differentiation link that provides new insight into skin homeostasis and cancer. It might constitute a self-defence mechanism against oncogenic alterations such as Myc deregulation

Fizikalni mehanizmi i metode u tumorskim terapijama i prijenosu lijekova do tumora

In addition to several well-known drug delivery strategies developed to facilitate effective chemotherapy with anticancer agents, some new approaches have been recently established, based on specific effects arising from the applications of ultrasound, magnetic and electric fields on drug delivery systems. This paper gives an overview of newly developed methods of drug delivery to tumors and of the related anticancer therapies based on the combined use of different physical methods and specific drug carriers. The conventional strategies and new approaches have been put into perspective to revisit the existing and to propose new directions to overcome the threatening problem of cancer diseases.Osim dobro poznatih metoda prijenosa lijekova u kemoterapijskom pristupu liječenja tumora, nedavno su otkriveni novi načini prijenosa koji se zasnivaju na specifičnim mehanizmima uzrokovanim upotrebom ultrazvuka, magnetskih i električnih polja. Članak sadrži prikaz fizikalnih mehanizama na kojima se temelje ove nove metode, kao i pregled novootkrivenih prijenosnika lijekova (Pluronske micele, magnetoliposomi, magnetski fluidi), novih terapija tumora (magnetska hipertermija, elektrokemoterapija) i najnovijih istraživanja temeljenih na fizikalnom pristupu ovoj problematici

Occurrence of arbuscular mycorrhizal fungi and nodules in the roots of twelve legume species in South-Western Saudi Arabia

The tripartite associations of arbuscular mycorrhizal fungi (AMF), rhizobia and legumes play a vital role in preserving and even restoring fertility of poor and eroded soils. The present study attempted to quantify relationship between legumes and symbiotic microorganisms (rhizobia and mycorrhizal fungi) by describing the mycorrhizal status and the occurrence of nodualtion of legumes growing in different areas of Jazan. The effect of legume species on soil microbial biomass was also investigated. Mycorrhizal and nodulation intensity varied greatly between legume species. The higher number of nodules (14 nodules per plant) and mycorrhization intensity (54%) were registered in root of Argyrolobium arabicum. Rhizosphere soils of all legume species harbored higher AMF fungal spores than bulk soils. Our results suggest also a significant effect of legumes species on soil microbial biomass. Thus, legume species investigated in this study are potentially useful for replanting and soil protection of most degraded regions of Saudi Arabia