Cancer is a multifactorial, multi-stage disease, including complex cascades of signaling pathways—the cell growth governed by dysregulated and abrupt cell division. Due to the complexity and multi-regulatory cancer progression, cancer is still a challenging disease to treat and survive. The screening of extracts and fractions from plants and marine species might lead to the discovery of more effective compounds for cancer therapeutics. The isolated compounds and reformed analogs were known as future prospective contenders for anti-cancer chemotherapy. For example, Taxol, a potent mitotic inhibitor discovered from Taxus brevifolia, suppresses cell growth and arrest, induces apoptosis, and inhibits proliferation. Similarly, marine sponges show remarkable tumor chemo preventive and chemotherapeutic potential. However, there is limited research to date. Several plants and marine-derived anti-cancer compounds having the property to induce apoptosis have been approved for clinical trials. The anti-cancer activity kills the cell and slows the growth of cancer cells. Among cell death mechanisms, apoptosis induction is a more profound mechanism of cell death triggered by naturally isolated anti-cancer agents. Evading apoptosis is the major hurdle in killing cancer cells, a mechanism mainly regulated as intrinsic and extrinsic. However, it is possible to modify the apoptosis-resistant phenotype of the cell by altering many of these mechanisms. Various extracts and fractions successfully induce apoptosis, cell-cycle modulation, apoptosis, and anti-proliferative activity. Therefore, there is a pressing need to develop new anti-cancer drugs of natural origins to reduce the effects on normal cells. Here, we’ve emphasized the most critical elements: i) A better understanding of cancer progression and development and its origins, ii) Molecular strategies to inhibit the cell proliferation/Carcino-genesis, iii) Critical regulators of cancer cell proliferation and development, iv) Signaling Pathways in Apoptosis: Potential Targets for targeted therapeutics, v) Why Apoptosis induction is mandatory for effective chemotherapy, vi) Plants extracts/fractions as potential apoptotic inducers, vii) Marine extracts as Apoptotic inducers, viii) Marine isolated Targeted compounds as Apoptotic inducers (FDA Approved/treatment Phase). This study provides a potential therapeutic option for cancer, although more clinical studies are needed to verify its efficacy in cancer chemotherapy.

• autophagy
• cancer
• genome instability
• hallmark
• macroenvironment
• microenvironment
• tumor

• LINC01272
• apoptosis
• lung cancer
• miR-7-5p/CRLS1
• multiplication

• Biomarker
• Head and neck cancer
• Personalized medicine
• Second primary cancer
• Single nucleotide polymorphism

• Biomarkers, Tumor/genetics
• Genetic Predisposition to Disease
• Head and Neck Neoplasms/genetics
• Humans
• Neoplasms, Second Primary/epidemiology
• Neoplasms, Second Primary/genetics
• Polymorphism, Single Nucleotide
• Risk Assessment/statistics & numerical data
• Risk Factors

• Linea D3.1 Università Cattolica del Sacro Cuore

• apoptosis
• innate immunity
• molecular pathways
• necrosis
• programmed cell death
• regulated

• Eurycoma longifolia Jack
• Pasak bumi
• Raji cells
• antiproliferation
• apoptosis
• cytotoxic
• p53 protein

• Animals
• Antineoplastic Agents/analysis
• Antineoplastic Agents/metabolism
• Plant Extracts/analysis
• Plant Extracts/metabolism
• Plant Extracts/pharmacology
• Plant Extracts/therapeutic use
• Quassins/analysis
• Quassins/metabolism
• Skates, Fish/metabolism

Platinum-based adjuvant chemotherapy is very common for gastric cancer (GC) patients, but the chemotherapy sensitivity is very heterogeneous. The genomic variants and the gene-gene interactions involved in Fas-mediated apoptosis pathway including Fas (FAS 1377 G > A and 670 A > G), FasL (FASL 844 C > T) and caspase-8 (CASP8 -652 6N ins > del or I > D), may paly vital roles in the response to platinum-based treatment. In our investigation, 662 stage II-III postoperative GC patients were enrolled between 1998 and 2006. 261 patients accepted platinum-based regimens and the remaining 401 were not. The log rank tests, Kaplan Meier plots, Pearson chi-square tests, Student t-tests and Cox regression analyses were performed. For the chemotherapy cohort, FAS 1377 G > A or FAS 670 A > G variants alone was related with inferior survival, and a greater than additive effect was identified when patients simultaneously carrying FAS 1377 GA and FAS 670 GA genotypes. But the poor response was neutralized when patients simultaneously carrying FASL 844 C > T or CASP8 -652 6N ins > del mutations. Our study suggested that FAS 1377 G > A and FAS 670 A > G variants may serve as potential biomarkers to predict the response to platinum-based adjuvant chemotherapy, and the gene-gene interactions involved in Fas-mediated apoptosis pathway may enhance or neutralize the chemosensitivity.

• Fas-mediated apoptosis
• chemotherapy
• gastric cancer (GC)
• genetic variants

Mast cell tumors (MCTs) are malignant neoplasms that are common in dogs. Their biological behavior is variable and unpredictable. The aim of the present study was to analyze the histological classification and expression of markers of canine MCTs.

Thirty samples of canine MCTs were graded according to the histological classification methods of Patnaik and those of Kiupel. The expression of phosphoprotein 53 (p53) and c-kit proteins was quantified by immunohistochemistry using image processing software, ImageJ - a public domain computer program, developed at the National Institutes of Health.

It was possible to determine the grade of 100% of the samples. According to Patnaik’s classification, 20.00% of the samples were Grade 1, 43.30% were Grade 2, and 36.70% were Grade 3. According to Kiupel’s classification, 56.67% of the samples were of high intensity and 43.33% were of low intensity. Grade 1 tumors had the highest expression of p53 and c-kit, and Grade 2 had the lowest expression. The results showed that it is necessary to perform both histological grading methods. The classification into high and low intensity may provide more consistent results than the three-level grading system. However, a smaller number of categories, although it facilitates the classification, may not be sufficient for the prognosis.

Quantitative evaluation of p-53 and c-kit expression is a useful tool to increase the accuracy of the analysis and to aid in choosing the treatment method for canine MCTs. Histological grading should be combined with other diagnostic methods.

• Bismarck brown
• ImageJ
• hematoxylin and eosin
• round cell tumor
• toluidine blue

Lung cancer is one of the most common and malignant cancers with extremely high morbidity and mortality in both males and females. Although traditional lung cancer treatments are fast progressing, there are still limitations. Caveolin-1 (Cav-1), a main component of caveolae, participates in multiple cellular events such as immune responses, endocytosis, membrane trafficking, cellular signaling and cancer progression. It has been found tightly associated with lung cancer cell proliferation, migration, apoptosis resistance and drug resistance. In addition to this, multiple bioactive molecules have been confirmed to target Cav-1 to carry on their anti-tumor functions in lung cancers. Cav-1 can also be a predictor for lung cancer patients’ prognosis. In this review, we have summarized the valuable research on Cav-1 and lung cancer in recent years and discussed the multifaceted roles of Cav-1 on lung cancer occurrence, development and therapy, hoping to provide new insights into lung cancer treatment.

• Caveolin-1 (Cav-1)
• lung cancer
• metastasis
• targeted therapy
• tumor progression

• cell cycle
• chemo-therapy
• cruciferous vegetables
• glucosinolates
• growth arrest
• isothiocyanates
• malignant melanoma
• skin cancer

• Chinese medicine
• G1/S arrest
• Ilex hainanensis Merr.
• anti-melanoma activity
• apoptosis
• caspase
• survival time

• Cervical cancer
• EVER
• FAS
• Polymorphism

• LDOC-1 gene
• RT-qPCR
• prostate cancer
• protein expression

The association between the increased risk of acute myeloid leukemia (AML) and Fas promoter polymorphisms has been reported previously; however, the results are inconclusive. The present study performed one case-control study to investigate the association, and a total of 98 AML patients and 2,014 healthy controls were genotyped. The data showed that the distribution of Fas-670AA, GA and GG genotypes among the AML patients were not significantly different from those of the healthy controls, all P>0.05. Following this a sub-study was conducted to analyze individuals who neither smoked nor drank. The results demonstrated that there was still no significant association between the Fas-670 polymorphism and risk of AML development, all P>0.05. Furthermore, in order to address a more accurate estimation of the association, a meta-analysis was conducted. Data were systematically collected from the Pubmed, EMBASE and the Wanfang Library. A total of 3 studies were included in this meta-analysis, which contained 1,144 AML cases and 3,806 controls. No significant association was detected between the Fas-670A>G polymorphism and AML risk [GA+GG vs. AA: odds ratio (OR) 0.93; 95% confidence interval (CI), 0.79–1.09; GG vs. AA: OR, 1.01; 95% CI, 0.82–1.24; GA vs. AA: OR, 1.12; 95% CI, 0.94–1.32; GG vs. AA+GA: OR, 0.94; 95% CI, 0.79–1.12; G vs. A: OR, 1.01; 95% CI, 0.91–1.12; all P>0.05). The analysis clearly indicated that there was no significant connection between the Fas-670A>G polymorphism and the increased risk of AML.

• Fas-670A>G polymorphism
• acute myeloid leukemia
• case-control study
• genotyping
• meta-analysis

FAS/FASL promoter variants are considered in altering transcriptional activity of those genes and consequently alter regulation of cell death. However, no studies have investigated whether tumor sites contribute to the association between FAS/FASL polymorphisms and risk for second primary malignancy (SPM).

In this study, FAS670 A > G, FAS1377 G > A, FASL124 A > G, and FASL844C > T polymorphisms were genotyped in 752 OPC and 777 non-OPC patients. Both univariate and multivariable cox proportional hazard models were used to assess the associations.

The univariate and multivariable analyses showed that patients with index OPC and FASL844 CT/TT genotype had significantly increased risk of SPM (cHR, 2.5; 95 % CI, 1.1–5.8, P = 0.043 and aHR, 2.7; 95 % CI, 1.2–6.0, P = 0.032) compared with those with FASL844 CC genotype as the reference group, while index non-OPC patients with FAS670 AG/GG and FasL844 CT/TT genotypes had significantly increased risk of SPM (cHR, 2.2 and 1.8; 95 % CI, 1.2–5.7 and 1.1–3.2; and P = 0.04 and 0.041, respectively and aHR, 2.4 and 1.7; 95 % CI, 1.1–5.1 and 1.0-3.0; and P = 0.043 and 0.049, respectively) compared with their corresponding AA and CC genotypes . Moreover, patients carrying more FAS/FASL variants significantly increased risk of SPM among index non-OPC patients. The stratified analysis showed that smoking status differently modified the associations between FAS/FASL polymorphisms and risk of SPM among index non-OPC from OPC patients.

These results suggested that FAS/FASL polymorphisms might significantly modify SPM risk among patients with SCCHN in a tumor site-specific manner.

• FAS and FASLG
• apoptosis
• biomarkers
• genetic variants
• head and neck cancer
• human papillomavirus
• oropharyngeal cancer
• recurrence

Plant sterols have shown potent anti-proliferative effects and apoptosis induction against breast and prostate cancers. However, the effect of sterols against hepatic cancer has not been investigated. In the present study, we assessed whether the stigmasterol isolated from Navicula incerta possesses apoptosis inductive effect in hepatocarcimona (HepG2) cells. According to the results, Stigmasterol has up-regulated the expression of pro-apoptotic gene expressions (Bax, p53) while down-regulating the anti-apoptotic genes (Bcl-2). Probably via mitochondrial apoptosis signaling pathway. With the induction of apoptosis caspase-8, 9 were activated. The DNA damage and increase in apoptotic cell numbers were observed through Hoechst staining, annexin V staining and cell cycle analysis. According to these results, we can suggest that the stigmasterol shows potent apoptosis inductive effects and has the potential to be tested as an anti-cancer therapeutic against liver cancer. [BMB Reports 2014; 47(8): 433-438]

Metastasis is a crucial hallmark of cancer progression, which involves numerous factors including the degradation of the extracellular matrix (ECM), the epithelial-to-mesenchymal transition (EMT), tumor angiogenesis, the development of an inflammatory tumor microenvironment, and defects in programmed cell death. Programmed cell death, such as apoptosis, autophagy, and necroptosis, plays crucial roles in metastatic processes. Malignant tumor cells must overcome these various forms of cell death to metastasize. This review summarizes the recent advances in the understanding of the mechanisms by which key regulators of apoptosis, autophagy, and necroptosis participate in cancer metastasis and discusses the crosstalk between apoptosis, autophagy, and necroptosis involved in the regulation of cancer metastasis.

• achillea biebersteinii
• apoptosis
• cancer
• green biosynthesis
• nano-silver

• Achillea/chemistry
• Apoptosis/drug effects
• Caspases/metabolism
• Flowers/chemistry
• Gene Expression Regulation, Neoplastic/drug effects
• Humans
• MCF-7 Cells
• Metal Nanoparticles/chemistry
• Neoplasms/drug therapy
• Neoplasms/metabolism
• Neoplasms/pathology
• Plant Extracts/chemistry
• Proto-Oncogene Proteins c-bcl-2/biosynthesis
• Silver/chemistry
• Silver/pharmacology
• bcl-2-Associated X Protein/biosynthesis

Single-nucleotide polymorphisms in apoptosis-related genes have been shown to play a role in the efficacy of platinum-based chemotherapy and may influence clinical outcomes. Our study aimed to evaluate the correlations of four functional single-nucleotide polymorphisms − FAS −670 A>G, FAS ligand −844 T>C, survivin −31 G>C, and survivin 9386 C>T – with drug response and clinical outcomes in advanced non-small-cell lung cancer patients who received platinum-based chemotherapy.

Polymorphisms were evaluated using the polymerase chain reaction-based restriction fragment-length polymorphism technique.

Patients with the CC genotype of FAS −670 A>G had worse overall survival (OS) than those with the CT or TT genotype (P=0.044), with median OS values of 20.1 months, 22.8 months, and 26.0 months, respectively. Furthermore, progression-free survival was associated with the FAS −670 A>G polymorphism (P=0.032). In addition, patients with the TC and CC genotypes of survivin 9386 C>T experienced improved survival compared with patients with the TT genotype (median OS 31.4 months and 22.8 months, respectively).

The functional FAS −670 A>G and survivin 9386 C>T polymorphisms are potential independent prognostic factors in advanced non-small-cell lung cancer patients treated with platinum-based chemotherapy.

• FAS −670 A>G
• chemotherapy response
• lung cancer
• polymorphism
• survivin 9386 C>T

Cyclins are essential for cell proliferation, the cell cycle and tumorigenesis in all eukaryotes. UbcH10 regulates the degradation of cyclins in a ubiquitin-dependent manner. Here, we report that UbcH10 is likely involved in tumorigenesis. We found that cancer cells exposed to n-acetyl-leu-leu-norleucinal (ALLN) treatment and UbcH10 depletion exhibit a synergistic therapeutic effect. Abundant expression of UbcH10 drives resistance to ALLN-induced cell death, while cells deficient in UbcH10 were susceptible to ALLN-induced cell death. The depletion of UbcH10 hindered tumorigenesis both in vitro and in vivo, as assessed by colony formation, growth curve, soft agar and xenograft assays. These phenotypes were efficiently rescued through the introduction of recombinant UbcH10. In the UbcH10-deficient cells, alterations in the expression of cyclins led to cell cycle changes and subsequently decreases in tumorigenesis. The tumorigenesis of xenograft tumors from UbcH10-deficient cells treated with ALLN was decreased relative to wild-type cells treated with ALLN in nude mice. On the molecular level, we observed that UbcH10 deficiency enhances the activation of caspase 8 and caspase 3 but not caspase 9 to impair cell viability upon ALLN treatment. Collectively, our results suggest that, as an oncogene, UbcH10 is a potential drug target for the treatment of colorectal cancer.

• FAS-670
• cervical carcinogenesis
• meta-analysis

• Adult
• Apoptosis
• Carcinoma/ethnology
• Carcinoma/genetics
• Case-Control Studies
• Ethnicity
• Fas Ligand Protein/genetics
• Female
• Gallbladder Neoplasms/ethnology
• Gallbladder Neoplasms/genetics
• Genetic Predisposition to Disease
• Haplotypes
• Humans
• India
• Middle Aged
• Polymorphism, Single Nucleotide
• Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics
• Risk
• fas Receptor/genetics

Recently, much attention has been given to discovering natural compounds as potent anti-cancer candidates. In the present study, the anti-cancer effects of fumigaclavine C, isolated from a marine-derived fungus, Aspergillus fumigatus, was evaluated in vitro. In order to investigate the impact of fumigaclavine C on inhibition of proliferation and induction of apoptosis in breast cancer, MCF-7 cells were treated with various concentrations of fumigaclavine C, and fumigaclavine C showed significant cytotoxicity towards MCF-7 cells. Anti-proliferation was analyzed via cell mobility and mitogen-activated protein kinase (MAPK) signaling pathway. In addition, fumigaclavine C showed potent inhibition on the protein and gene level expressions of MMP-2, -9 in MCF-7 cells which were manifested in Western blot and reverse transcription polymerase chain reaction (RT-PCR) results. The apoptosis induction abilities of the fumigaclvine C was studied by analyzing the expression of apoptosis related proteins, cell cycle analysis, DNA fragmentation and molecular docking studies. It was found that fumigaclavine C fragmented the MCF-7 cell DNA and arrested the cell cycle by modulating the apoptotic protein expressions. Moreover, fumigaclavine C significantly down-regulated the NF-kappa-B cell survival pathway. Collectively, data suggest that fumigaclavine C has a potential to be developed as a therapeutic candidate for breast cancer.

The Fas rs180082 polymorphism has been reported to be associated with cervical cancer susceptibility, yet the results of these previous results have been inconsistent or controversial. The objective of this study was to explore whether the Fas rs180082 polymorphism confers susceptibility to cervical cancer.

The relevant studies were identified through a search of PubMed, Excerpta Medica Database (Embase), Elsevier Science Direct and Chinese Biomedical Literature Database (CBM) until July 2012. The association between the Fas rs180082 polymorphism and cervical cancer risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs).

A total of 7 case–control studies were eventually identified. We found no association between Fas rs180082 polymorphism and cervical cancer susceptibility in overall population (G versus A: OR = 1.03, 95% CI = 0.99-1.07, P = 0.197; AG + GG versus AA: OR = 1.04, 95% CI = 0.98-1.09, P = 0.176; GG versus AA + AG: OR = 1.04, 95% CI = 0.84–1.31, P = 0.701). In subgroup analysis, similar results were found in Asian (G versus A: OR = 1.06, 95% CI = 0.97–1.15, P = 0.195; AG + GG versus AA: OR = 1.08, 95% CI = 0.98–1.19, P = 0.176; GG versus AA + AG: OR = 0.97, 95% CI = 0.51–1.84, P = 0.935) and African (G versus A: OR = 1.01, 95% CI = 0.97-1.15, P = 0.195; AG + GG versus AA: OR = 0.99, 95% CI = 0.91–1.07, P = 0.739; GG versus AA + AG: OR = 1.09, 95% CI = 0.94–1.25, P = 0.745).

This meta-analysis has shown that there is a lack of association of the Fas rs180082 polymorphisms with cervical cancer susceptibility. However, larger scale primary studies with the consideration of gene–gene and gene–environment interactions are still required to further evaluate the interaction of Fas rs180082 polymorphism with cervical cancer susceptibility.

Yeast cells can be killed upon expression of pro-apoptotic mammalian proteins. We have established a functional yeast survival screen that was used to isolate novel human anti-apoptotic genes overexpressed in treatment-resistant tumors. The screening of three different cDNA libraries prepared from metastatic melanoma, glioblastomas and leukemic blasts allowed for the identification of many yeast cell death-repressing cDNAs, including 28% of genes that are already known to inhibit apoptosis, 35% of genes upregulated in at least one tumor entity and 16% of genes described as both anti-apoptotic in function and upregulated in tumors. These results confirm the great potential of this screening tool to identify novel anti-apoptotic and tumor-relevant molecules. Three of the isolated candidate genes were further analyzed regarding their anti-apoptotic function in cell culture and their potential as a therapeutic target for molecular therapy. PAICS, an enzyme required for de novo purine biosynthesis, the long non-coding RNA MALAT1 and the MAST2 kinase are overexpressed in certain tumor entities and capable of suppressing apoptosis in human cells. Using a subcutaneous xenograft mouse model, we also demonstrated that glioblastoma tumor growth requires MAST2 expression. An additional advantage of the yeast survival screen is its universal applicability. By using various inducible pro-apoptotic killer proteins and screening the appropriate cDNA library prepared from normal or pathologic tissue of interest, the survival screen can be used to identify apoptosis inhibitors in many different systems.

• Apoptosis/genetics
• Base Sequence
• Blotting, Western
• DNA Primers
• DNA, Complementary/genetics
• Gene Expression Profiling
• HEK293 Cells
• Humans
• Neoplasms/genetics
• Neoplasms/pathology
• Oncogenes
• Real-Time Polymerase Chain Reaction
• Schizosaccharomyces/genetics

• Wellcome Trust

A genetic background has been implicated in the development of prostate cancer. Protein microarrays have enabled the identification of proteins, some of which associated with apoptosis, that may play a role in the development of such a tumor. Inhibition of apoptosis is a co-factor that contributes to the onset and progression of prostate cancer, though the molecular mechanisms are not entirely understood. Poly (ADP-ribose) polymerase 1 (PARP-1) gene is required for translocation of the apoptosis-inducing factor (AIF) from the mitochondria to the nucleus. Hence, it is involved in programmed cell death. Different PARP-1 gene expression has been observed in various tumors such as glioblastoma, lung, ovarian, endometrial, and skin cancers. We evaluated the expression of PARP-1 protein in prostatic cancer and normal prostate tissues by immunohistochemistry in 40 men with prostate cancer and in 37 normal men. Positive nuclear PARP-1 staining was found in all samples (normal prostate and prostate cancer tissues). No cytoplasmic staining was observed in any sample. PARP-1-positive cells resulted significantly higher in patients with prostate carcinoma compared with controls (P<0.001). PARP-1 over-expression in prostate cancer tissue compared with normal prostate suggests a greater activity of PARP-1 in these tumors. These findings suggest that PARP-1 expression in prostate cancer is an attempt to trigger apoptosis in this type of tumor similarly to what reported in other cancers.

Bladder cancer is the most common malignancy of the urinary system. The incidence of bladder cancer of men is higher than that of women (approximately 4:1). Here, we summarize the bladder cancer-related risk factors, including environmental and genetic factors. In recent years, although the mortality rate induced by bladder cancer has been stable or decreased gradually, the public health effect may be pronounced. The well-established risk factors for bladder cancer are cigarette smoking and occupational exposure. Genetic factors also play important roles in the susceptibility to bladder cancer. A recent study demonstrated that hereditary non-polyposis colorectal cancer is associated with increased risk of bladder cancer. Since 2008, genome-wide association study (GWAS) has been used to identify the susceptibility loci for bladder cancer. Further gene-gene or gene-environment interaction studies need to be conducted to provide more information for the etiology of bladder cancer.

• bladder cancer
• genetic susceptibility
• molecular epidemiology
• risk factors

Cervical cancer is the second most common cancer in women worldwide. This is caused by oncogenic types of human papillomavirus (HPV) infection. Although large numbers of young sexually active women get HPV-infected, only a small fraction develop cervical cancer. This points to different co-factors for regression of HPV infection or progression to cervical cancer. Host genetic factors play an important role in the outcome of such complex or multifactor diseases such as cervical cancer and are also known to regulate the rate of disease progression. The aim of this review is to compile the advances in the field of host genetics of cervical cancer. MEDLINE database was searched using the terms, ‘HPV’, ‘cervical’, ‘CIN’, ‘polymorphism(s)’, ‘cervical’+ *the name of the gene* and ‘HPV’+ *the name of the gene*. This review focuses on the major host genes reported to affect the progression to cervical cancer in HPV infected individuals.

• Cervical cancer
• HPV
• genetics
• polymorphism
• progression

Although oligomeric β-amyloid (Aβ) has been suggested to have an important role in Alzheimer disease (AD), the mechanism(s) of how Aβ induces neuronal cell death has not been fully identified. The balance of pro- and anti-apoptotic Bcl-2 family proteins (e.g., Bcl-2 and Bcl-w versus Bad, Bim and Bax) has been known to have a role in neuronal cell death and, importantly, expression levels of these proteins are reportedly altered in the vulnerable neurons in AD. However, the roles of apoptotic proteins in oligomeric Aβ-induced cell death remain unclear in vivo or in more physiologically relevant models. In addition, no study to date has examined whether Bax is required for the toxicity of oligomeric Aβ. Here, we found that treatment with oligomeric Aβ increased Bim levels but decreased Bcl-2 levels, leading to the activation of Bax and neuronal cell death in hippocampal slice culture and in vivo. Furthermore, the inhibition of Bax activity either by Bax-inhibiting peptide or bax gene knockout significantly prevented oligomeric Aβ-induced neuronal cell death. These findings are first to demonstrate that Bax has an essential role in oligomeric Aβ-induced neuronal cell death, and that the targeting of Bax may be a therapeutic approach for AD.

Dysregulation of many apoptotic related genes and androgens are critical in the development, progression, and treatment of prostate cancer. The differential sensitivity of tumour cells to TRAIL-induced apoptosis can be mediated by the modulation of surface TRAIL receptor expression related to androgen concentration. Our previous results led to the hypothesis that downregulation of TRAIL-decoy receptor DcR2 expression following androgen deprivation would leave hormone sensitive normal prostate cells vulnerable to the cell death signal generated by TRAIL via its pro-apoptotic receptors. We tested this hypothesis under pathological conditions by exploring the regulation of TRAIL-induced apoptosis related to their death and decoy receptor expression, as also to hormonal concentrations in androgen-sensitive human prostate cancer, LNCaP, cells.

In contrast to androgen-insensitive PC3 cells, decoy (DcR2) and death (DR5) receptor protein expression was correlated with hormone concentrations and TRAIL-induced apoptosis in LNCaP cells. Silencing of androgen-sensitive DcR2 protein expression by siRNA led to a significant increase in TRAIL-mediated apoptosis related to androgen concentration in LNCaP cells.

The data support the hypothesis that hormone modulation of DcR2 expression regulates TRAIL-induced apoptosis in LNCaP cells, giving insight into cell death induction in apoptosis-resistant hormone-sensitive tumour cells from prostate cancer. TRAIL action and DcR2 expression modulation are potentially of clinical value in advanced tumour treatment.

• Adult
• Aged
• Aged, 80 and over
• Alleles
• Fas Ligand Protein/genetics
• Female
• Gastritis, Atrophic/genetics
• Gastritis, Atrophic/microbiology
• Genotype
• Helicobacter Infections/complications
• Helicobacter pylori
• Humans
• Male
• Middle Aged
• Nod1 Signaling Adaptor Protein/genetics
• Peptidyl-Dipeptidase A/genetics
• Polymorphism, Genetic
• Precancerous Conditions/genetics
• Risk Factors
• Stomach Neoplasms/ethnology
• Stomach Neoplasms/genetics
• Stomach Neoplasms/microbiology
• Toll-Like Receptor 4/genetics
• White People/genetics
• fas Receptor/genetics

It is widely accepted that specific human papillomavirus (HPV) types are the central etiologic agent of cervical carcinogenesis. However, a number of infected women do not develop invasive lesions, suggesting that other environmental and host factors may play decisive roles in the persistence of HPV infection and further malignant conversion of cervical epithelium. Although many previous reports have focused on HPV and environmental factors, the role of host susceptibility to cervical carcinogenesis is largely unknown. Here, we review the findings of genetic association studies in cervical carcinogenesis with special reference to polymorphisms of glutathione-S-transferase (GST) isoforms, p53 codon 72, murine double-minute 2 homolog (MDM2) gene promoter 309, and FAS gene promoter -670 together with HPV types including our recent research results.

• fas/faslg
• squamous cell carcinoma of head and neck
• second primary malignancy
• genetic susceptibility
• polymorphism

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Squamous Cell/genetics
• Carcinoma, Squamous Cell/pathology
• Disease Progression
• Fas Ligand Protein/genetics
• Female
• Gene Frequency
• Genetic Predisposition to Disease
• Head and Neck Neoplasms/genetics
• Head and Neck Neoplasms/pathology
• Humans
• Male
• Middle Aged
• Neoplasms, Second Primary/genetics
• Neoplasms, Second Primary/pathology
• Polymorphism, Genetic
• Polymorphism, Single Nucleotide
• Risk Factors
• Young Adult
• fas Receptor/genetics

• P30 CA016672 NCI NIH HHS
• R01 ES011740 NIEHS NIH HHS
• R01 ES-11740 NIEHS NIH HHS
• K07 CA133099 NCI NIH HHS
• P-30 CA-16672 NCI NIH HHS
• CA133099 NCI NIH HHS
• CA135679 NCI NIH HHS
• R03 CA135679 NCI NIH HHS

• ck2
• casein kinase 2
• ckii
• cancer
• ck2 dysregulation
• ck2 upregulation
• prognostic marker
• therapeutic target
• nanoparticle
• nanocapsule

• Animals
• Antineoplastic Agents/therapeutic use
• Apoptosis/physiology
• Casein Kinase II/antagonists & inhibitors
• Casein Kinase II/physiology
• Cell Line, Tumor
• Cell Proliferation
• Cell Transformation, Neoplastic/metabolism
• Cell Transformation, Neoplastic/pathology
• Humans
• Neoplasm Transplantation
• Neoplasms/drug therapy
• Neoplasms/enzymology
• Neoplasms/pathology
• Protein Kinase Inhibitors/pharmacology
• Protein Kinase Inhibitors/therapeutic use
• Signal Transduction/physiology
• Transplantation, Heterologous

• R01 CA015062 NCI NIH HHS
• U01 CA015062 NCI NIH HHS
• CA-15062 NCI NIH HHS

• cancer
• energy depression
• hypoxia
• inflammation
• mitochondria
• mitochondrial cell death
• neurodegenerative diseases

• Adenosine Triphosphate/metabolism
• Apoptosis/physiology
• Cell Proliferation
• Cell Survival/physiology
• Energy Metabolism/genetics
• Glycolysis/physiology
• Mitochondria/genetics
• Mitochondria/metabolism
• Mitochondria/pathology
• Mitochondrial Diseases/genetics
• Mitochondrial Diseases/metabolism
• Neurodegenerative Diseases/genetics
• Neurodegenerative Diseases/metabolism
• Oxidative Phosphorylation

• Animals
• Cervix Uteri/physiology
• Cervix Uteri/virology
• Female
• Gene Expression Profiling
• Human papillomavirus 16
• In Situ Hybridization
• Mice
• Mice, Transgenic
• Oligonucleotide Array Sequence Analysis
• Oncogene Proteins, Viral/genetics
• Repressor Proteins/genetics
• Reverse Transcriptase Polymerase Chain Reaction
• Skin/virology

• R01 CA098428 NCI NIH HHS

• Active Transport, Cell Nucleus/physiology
• CD47 Antigen/genetics
• CD47 Antigen/metabolism
• Caspases/metabolism
• Cell Death/physiology
• Cell Shape
• Cells, Cultured
• Dynamins
• Electron Transport/physiology
• GTP Phosphohydrolases/genetics
• GTP Phosphohydrolases/metabolism
• Humans
• Leukemia/metabolism
• Microtubule-Associated Proteins/genetics
• Microtubule-Associated Proteins/metabolism
• Mitochondria/metabolism
• Mitochondria/pathology
• Mitochondrial Proteins/genetics
• Mitochondrial Proteins/metabolism
• Proto-Oncogene Proteins c-bcl-2/genetics
• Proto-Oncogene Proteins c-bcl-2/metabolism
• Serine Endopeptidases/metabolism
• T-Lymphocytes/cytology
• T-Lymphocytes/physiology