Fucoidan extract (FE), an enzymatically digested compound with a low molecular weight, is extracted from brown seaweed. As a natural compound with various actions, FE is attractive, especially in ...Asian countries, for improving the therapeutic efficacy and safety of cancer treatment. The present study was carried out to investigate the anti-tumor properties of FE in human carcinoma cells and further examine the underlying mechanisms of its activities.
FE inhibits the growth of MCF-7, MDA-MB-231, HeLa, and HT1080 cells. FE-mediated apoptosis in MCF-7 cancer cells is accompanied by DNA fragmentation, nuclear condensation, and phosphatidylserine exposure. FE induces mitochondrial membrane permeabilization (MMP) through loss of mitochondrial membrane potential (ΔΨm) and regulation of the expression of Bcl-2 family members. Release of apoptosis-inducing factor (AIF) and cytochrome c precedes MMP. AIF release causes DNA fragmentation, the final stage of apoptosis, via a caspase-independent mitochondrial pathway. Additionally, FE was found to induce phosphorylation of c-Jun N-terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK) 1/2, and apoptosis was found to be attenuated by inhibition of JNK. Furthermore, FE-mediated apoptosis was found to involve the generation of reactive oxygen species (ROS), which are responsible for the decrease of ΔΨm and phosphorylation of JNK, p38, and ERK1/2 kinases.
These data suggest that FE activates a caspase-independent apoptotic pathway in MCF-7 cancer cells through activation of ROS-mediated MAP kinases and regulation of the Bcl-2 family protein-mediated mitochondrial pathway. They also provide evidence that FE deserves further investigation as a natural anticancer and cancer preventive agent.
Fucoidan, a fucose-rich polysaccharide extracted from brown seaweed, has antitumor, anticoagulant, antiviral, anti-inflammatory, and antibacterial activities. Several studies have shown that a ...fucoidan treatment of cancer cells induced cytotoxicity and apoptosis and inhibited angiogenesis and invasion. We investigated in the present study the effect of low-molecular-weight fucoidan (LMWF) on apoptosis in estrogen receptor-negative MDA-MB-231 human breast cancer cells. The LMWF treatment of MDA-MB-231 cells was associated with the activation of caspases and mitochondrial dysfunction, including dissipation of the mitochondrial membrane potential (ΔΨm), alteration of Ca(2+) homeostasis, cytochrome c release, and decreased expression of antiapoptotic Bcl-2 family proteins. Understanding the molecular events that mediated LMWF-induced MDA-MB-231 cell death will contribute to a more rational approach to cancer chemotherapy.
Low molecular weight fucoidan extract (LMF), prepared by an abalone glycosidase digestion of a crude fucoidan extracted from
Kylin, exhibits various biological activities, including anticancer ...effect. Various cancers express programmed cell death-ligand 1 (PD-L1), which is known to play a significant role in evasion of the host immune surveillance system. PD-L1 is also expressed in many types of normal cells for self-protection. Previous research has revealed that selective inhibition of PD-L1 expressed in cancer cells is critical for successful cancer eradication. In the present study, we analyzed whether LMF could regulate PD-L1 expression in HT1080 fibrosarcoma cells. Our results demonstrated that LMF suppressed PD-L1/PD-L2 expression and the growth of HT1080 cancer cells and had no effect on the growth of normal TIG-1 cells. Thus, LMF differentially regulates PD-L1 expression in normal and cancer cells and could serve as an alternative complementary agent for treatment of cancers with high PD-L1 expression.
This paper studies generalized variants of the MAXIMUM INDEPENDENT SET problem, called the Maximum Distance -d Independent Set problem (MaxDdIS for short). For an integer d≥2, a distance-d ...independent set of an unweighted graph G=(V, E) is a subset S⊆V of vertices such that for any pair of vertices u, v∈S, the number of edges in any path between u and v is at least d in G. Given an unweighted graph G, the goal of MaxDdIS is to find a maximum-cardinality distance-d independent set of G. In this paper, we analyze the (in)approximability of the problem on r-regular graphs (r≥3) and planar graphs, as follows: (1) For every fixed integers d≥3 and r≥3, MaxDdIS on r-regular graphs is APX-hard. (2) We design polynomial-time O(rd-1)-approximation and O(rd-2/d)-approximation algorithms for MaxDdIS on r-regular graphs. (3) We sharpen the above O(rd-2/d)-approximation algorithms when restricted to d=r=3, and give a polynomial-time 2-approximation algorithm for MaxD3IS on cubic graphs. (4) Finally, we show that MaxDdIS admits a polynomial-time approximation scheme (PTAS) for planar graphs.
Fucoidan, a fucose-rich polysaccharide isolated from brown alga, is currently under investigation as a new anti-cancer compound. In the present study, fucoidan extract (FE) from Cladosiphon ...navae-caledoniae Kylin was prepared by enzymatic digestion. We investigated whether a combination of FE with cisplatin, tamoxifen or paclitaxel had the potential to improve the therapeutic efficacy of cancer treatment. These co-treatments significantly induced cell growth inhibition, apoptosis, as well as cell cycle modifications in MDA-MB-231 and MCF-7 cells. FE enhanced apoptosis in cancer cells that responded to treatment with three chemotherapeutic drugs with downregulation of the anti-apoptotic proteins Bcl-xL and Mcl-1. The combination treatments led to an obvious decrease in the phosphorylation of ERK and Akt in MDA-MB-231 cells, but increased the phosphorylation of ERK in MCF-7 cells. In addition, we observed that combination treatments enhanced intracellular ROS levels and reduced glutathione (GSH) levels in breast cancer cells, suggesting that induction of oxidative stress was an important event in the cell death induced by the combination treatments.
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a proapoptotic member of the TNF family of type II membrane proteins, which constitutes one component of T cell cytotoxicity. ...In this study, we investigated the expression and function of TRAIL in human peripheral blood T (PBT) cells. Although freshly isolated PBT cells did not express a detectable level of TRAIL on their surface, a remarkable TRAIL expression was rapidly induced on the surface of both CD4(+) and CD8(+) PBT cells upon stimulation with anti-CD3 monoclonal antibody and type I interferons (IFNs). This enhancement of TRAIL expression was a unique feature of type I IFNs (IFN-alpha and IFN-beta), and neither type II IFN (IFN-gamma) nor various other cytokines enhanced TRAIL expression on anti-CD3-stimulated PBT cells. Type I IFNs have been used for clinical treatment of renal cell carcinomas (RCCs), and we found that most RCC cell lines were susceptible to TRAIL-induced apoptosis. Type I IFNs substantially augmented cytotoxic activity of anti-CD3-stimulated PBT cells against RCC cell lines in a TRAIL-dependent manner. These results indicate a unique feature of type I IFNs to regulate TRAIL-mediated T cell cytotoxicity, which may be involved in the antitumor effects of type I IFNs against various tumors.
The cut-set
∂
(
S
)
of a graph
G
=
(
V
,
E
)
is the set of edges that have one endpoint in
S
⊂
V
and the other endpoint in
V
\
S
, and whenever
G
S
is connected, the cut
S
,
V
\
S
of
G
is called ...a connected cut. A bond of a graph
G
is an inclusion-wise minimal disconnecting set of
G
, i.e., bonds are cut-sets that determine cuts
S
,
V
\
S
of
G
such that
G
S
and
G
V
\
S
are both connected. Contrasting with a large number of studies related to maximum cuts, there exist very few results regarding the largest bond of general graphs. In this paper, we aim to reduce this gap on the complexity of computing the largest bond, and the maximum connected cut of a graph. Although cuts and bonds are similar, we remark that computing the largest bond and the maximum connected cut of a graph tends to be harder than computing its maximum cut. We show that it does not exist a constant-factor approximation algorithm to compute the largest bond, unless
P
=
NP
. Also, we show that
Largest Bond
and
Maximum Connected Cut
are NP-hard even for planar bipartite graphs, whereas
Maximum Cut
is trivial on bipartite graphs and polynomial-time solvable on planar graphs. In addition, we show that
Largest Bond
and
Maximum Connected Cut
are NP-hard on split graphs, and restricted to graphs of clique-width
w
they can not be solved in time
f
(
w
)
n
o
(
w
)
unless the Exponential Time Hypothesis fails, but they can be solved in time
f
(
w
)
n
O
(
w
)
. Finally, we show that both problems are fixed-parameter tractable when parameterized by the size of the solution, the treewidth, and the twin-cover number.
In this paper, we study a variant of the M inimum D ominating S et problem. Given an unweighted undirected graph G=(V,E) of n=|V| vertices, the goal of the M inimum S ingle D ominating C ycle problem ...(MinSDC) is to find a single shortest cycle which dominates all vertices, i.e., a cycle C such that for the set V(C) of vertices in C and the set N(V(C)) of neighbor vertices of C, V(G)=V(C)∪N(V(C)) and |V(C)| is minimum over all dominating cycles in G 6, 17, 24. In this paper we consider the (in)approximability of MinSDC if input graphs are restricted to some special classes of graphs. We first show that MinSDC is still NP-hard to approximate even when restricted to planar, bipartite, chordal, or r-regular (r≥3). Then, we show the (lnn+1)-approximability and the (1-ε)lnn-inapproximability of MinSDC on split graphs under P≠NP. Furthermore, we explicitly design a linear-time algorithm to solve MinSDC for graphs with bounded treewidth and estimate the hidden constant factor of its running time-bound.
OBJECTIVES
To investigate the efficacy of maximum androgen blockade (MAB) using flutamide as second‐line hormonal therapy for advanced hormone‐refractory prostate cancer (HRPC).
PATIENTS AND METHODS
...The study included 55 patients with HRPC who were treated with MAB using flutamide (375 mg daily) as second‐line hormonal therapy. All patients had previously received bicalutamide combined with either surgical or medical castration as first‐line hormonal therapy, which failed. The effect of the second‐line therapy was evaluated by serum prostate‐specific antigen (PSA) level alone, and the response defined as a decrease of >50% from the baseline PSA at the start of second‐line therapy.
RESULTS
On initiating second‐line hormonal therapy there was a reduction in the PSA level in 25 of the 55 patients (45%), among whom 12 (22%) were regarded as responders, while the PSA level continued to increase in the remaining 30 (55%). The median (range) duration of the PSA response was 6 (1–13) months. During the observation period there were no severe side‐effects from the second‐line MAB therapy. Patients without bone metastases or whose disease progressed >1 year after first‐line therapy had a significantly higher incidence of PSA response to second‐line therapy, despite no significant effect of other factors examined on the PSA response to second‐line therapy. Furthermore, the cause‐specific survival in responders to second‐line therapy was significantly better than that in nonresponders; however, multivariate analysis showed that no factors, including response to second‐line therapy, could be used as independent predictors of cause‐specific survival.
CONCLUSIONS
MAB using flutamide as second‐line hormonal therapy can give a comparatively favourable PSA response with no severe side‐effects; therefore, this therapy may be suitable for patients with HRPC after primary MAB using bicalutamide has failed, particularly in those with no bone metastases or whose disease has progressed for >1 year after first‐line therapy.
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