卷 10, 编号 6 (2010)

Induction of caspase-dependent apoptosis (type I cell death) is a major mechanism by which most chemotherapeutic drugs and radiation kill tumor cells. However, conventional cancer therapies fail to mediate their effects in a target-specific fashion. The extremely unfavorable prognosis for patients suffering from glioblastomas (GBMs) is strongly correlated to the intrinsic apoptosis resistance of GBM cells which especially occurs in diffusely migrating tumor cells. The ultimate goal for molecular, apoptosis-based therapies is to target specific components of the two major apoptotic pathways, i.e. the extrinsic and the intrinsic pathway to trigger tumor-selective apoptosis, while at the same time limiting toxicity in normal tissues. Induction of autophagic cell death (type II cell death) by proautophagic drugs is an alternative and emerging concept to trigger glioma cell death and to exploit caspase-independent programmed cell death pathways for the development of novel glioma therapies. This review provides an up to date and comprehensive report on the relevant pre-clinical and clinical drugs interfering with the major apoptosis and autophagy pathways, their therapeutic potential in glioma and adresses potential future perspectives in this exciting field of research.

Immunotherapy of brain tumors is rapidly emerging as a potential clinical option [1-3]. The quality and magnitude of immune responses evoked by the new generation anti-tumor vaccines is in general highly dependent on the source or choice of peptide antigens, and as well, a suitable immunopotentiator. Poorly immunogenic antigens, such as those present in tumor cell lysates, may not reliably provide stimulation like recombinant or DNA-encoded protein antigens might be expected to. In addition, the efficacy of the vaccine may depend on inherent counteracting measures of the tumor which dampen immune surveillance and immune effector activity triggered by immunization [4]. Our body has many means of limiting an immune response to our own (self) proteins. In particular, patients with gliomas exhibit a broad suppression of cell-mediated immunity [5-8]. Unfortunately, for most tumor vaccines the induction of local or systemic immune effector cells does not necessarily translate into objective clinical responses or increased survival [9]. Here we review immunotherapeutic approaches against gliomas and recent pre-clinical and clinical initiatives based on cellular or active immunization of the patients immune system using autologous and allogeneic tissues or cultured cells. Available evidence shows that single modality cancer therapies likely remain suboptimal. Combination regimens targeting the immune system at multiple coordinated levels must be developed, and possibly combined with strategies to inhibit immune suppressive factors if significant clinical benefit is to be achieved.

Obesity has been recognized as an important risk factor for many serious medical conditions. The association of obesity with an increased risk of many cancers is of enormous economic importance to the health industry.The metabolic syndrome and visceral obesity have an increasing prevelance and incidence in the general population.The actual prevelance of the metabolic syndrome is 24% in US population and between 24.6% and 30.9% in Europe. Recent evidence from epidemiologic and basic research studies, as well as clinical and intervention studies, supports the emerging hypothesis that metabolic syndrome may be an important etiologic factor for the onset of cancer. In addition, increased body weight has recently been shown to be associated with an increased risk of cancers at multiple specific sites. The close interaction between cancer cells and adipocytes is an intriguing issue in tumor biology. In nowdays, several metabolic markers are implicated in the development and progression of several malignancies. This review describes the emerging data concerning the role of metabolic markes in tumor cell growth and relates them to their future clinical prospects.

Arsenic trioxide (ATO) has shown great promise in the treatment of patients with relapsed or refractory acute promyelocytic leukemia (APL). However, the risk/benefit ratios of ATO in hematologic malignancies other than APL are still unclear. In this review, the author attempts to provide current experimental and clinical challenges to gain more knowledge of the effects of ATO by examining combination therapies with other agents, especially for non-APL hematologic malignancies, such as acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), chronic myeloid leukemia (CML), chronic lymphoid leukemia (CLL) and multiple myeloma (MM). The drugs combined with ATO can be roughly classified into (1) signaling inhibitors (imatinib, PD184352, LY294002, 17-Allylamino- 17-demethoxygeldanamycin: 17-AAG), (2) oxidative stress pathway modulators (ascorbic acid, 2-methoxyestradiol: 2-ME, dlbuthionine-[ S,R]-sulfoximine: BSO), (3) a chemotherapeutic drug (melphalan) and (4) others (bortezomib, ATRA). Some of these combination therapies have shown promising results in MM not only at the experimental level but also at the clinical level. However, studies are still ongoing for other non-APL hematologic malignancies. Since ATO is well tolerated and its toxicities are manageable and reversible, cell type-specific and efficient combination therapies with ATO are advantageous for non-APL hematological malignancies and should be developed in the near future.