Molecular landscape of esophageal cancer: implications for early detection and personalized therapy.

Esophageal cancer (EC) is one of the most lethal cancers and a public health concern worldwide, owing to late diagnosis and lack of efficient treatment. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are main histopathological subtypes of EC that show striking differences in geographical distribution, possibly due to differences in exposure to risk factors and lifestyles. ESCC and EAC are distinct diseases in terms of cell of origin, epidemiology, and molecular architecture of tumor cells.

Mono- and multimeric ferrocene congeners of quinoline-based polyamines as potential antiparasitics.

A series of mono- and multimeric polyamine-containing ferrocenyl complexes containing a quinoline motif were prepared. The complexes were characterised by standard techniques. The molecular structure of the monomeric salicylaldimine derivative was elucidated using single crystal X-ray diffraction and was consistent with the proposed structure.

NDRG1 overexpression promotes the progression of esophageal squamous cell carcinoma through modulating Wnt signaling pathway.

N-myc down-regulated gene 1 (NDRG1) has been shown to regulate tumor growth and metastasis in various malignant tumors and also to be dysregulated in esophageal squamous cell carcinoma (ESCC). Here, we show that NDRG1 overexpression (91.9%, 79/86) in ESCC tumor tissues is associated with poor overall survival of esophageal cancer patients.

Polyamine quinoline rhodium complexes: synthesis and pharmacological evaluation as antiparasitic agents against Plasmodium falciparum and Trichomonas vaginalis.

A series of mono- and bis-salicylaldimine ligands and their corresponding Rh(i) complexes were prepared. The compounds were characterised using standard spectroscopic techniques including NMR, IR spectroscopy and mass spectrometry. The salicylaldimine ligands and complexes were screened for antiparasitic activity against two strains of Plasmodium falciparum i.

Elevated expression of the nuclear export protein, Crm1 (exportin 1), associates with human oesophageal squamous cell carcinoma.

The nuclear export receptor, Crm1 (exportin 1), is involved in the nuclear translocation of proteins and certain RNAs from the nucleus to the cytoplasm and is thus crucial for the correct localisation of cellular components. Crm1 has recently been reported to be highly expressed in certain types of cancers, yet its expression in oesophageal cancer has not been investigated to date. We investigated the expression of Crm1 in normal and tumour tissues derived from 56 patients with human oesophageal squamous cell carcinoma and its functional significance in oesophageal cancer cell line models.

Use of NQO1 status as a selective biomarker for oesophageal squamous cell carcinomas with greater sensitivity to 17-AAG.

Background: Oesophageal squamous cell carcinoma (OSCC) is a major health burden in Sub-Saharan Africa, and novel chemotherapies are urgently required to combat this disease. The heat shock protein 90 (HSP90) inhibitor 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) has previously been proposed as a possible candidate drug. NADPH quinone oxidoreductase 1 (NQO1) is known to increase the potency of 17-AAG, therefore we investigated the effects of 17-AAG in OSCC cell lines in the context of their NQO1 status.

Synthesis, characterization, antiparasitic and cytotoxic evaluation of thioureas conjugated to polyamine scaffolds.

A series of mono- and multimeric 4-amino-7-chloroquinoline and ferrocenyl thioureas have been prepared by the reaction of a 7-chloroquinoline methyl ester and a ferrocenylimine methyl ester with various amines. These compounds were characterized using standard spectroscopic and analytical techniques. The compounds were evaluated against the NF54 (CQ-sensitive) and Dd2 (CQ-resistant) strains of Plasmodium falciparum.

Cytotoxicity of lapachol, β-lapachone and related synthetic 1,4-naphthoquinones against oesophageal cancer cells.

Naphthoquinones have been found to have a wide range of biological activities, including cytotoxicity to cancer cells. The secondary metabolites lapachol, α- and β-lapachone and a series of 25 related synthetic 1,4-naphthoquinones were screened against the oesophageal cancer cell line (WHCO1). Most of the compounds exhibited enhanced cytotoxicity (IC50 1.

1-(Thio-phen-2-yl)-N-(4-{(E)-[(thio-phen-2-yl)meth-yl]imino-meth-yl}benzyl-idene)methanamine.

The title compound C(18)H(16)N(2)S(2), crystallizes with two independent half-mol-ecules in the asymmetric unit, in one of which the thio-phene rings are disordered in a 0.67:0.33 ratio.

Oncogenic but non-essential role of N-myc downstream regulated gene 1 in the progression of esophageal squamous cell carcinoma.

N-myc downstream regulated gene 1 (NDRG1/Cap43/Drg-1) has previously been shown to be dysregulated in esophageal squamous cell carcinoma (ESCC). In this study, we investigated the role of NDRG1 in the neoplastic progression of ESCC using ectopic gain-of-function and loss-of-function approaches. Stable transfectants of the KYSE30 ESCC cell line with altered NDRG1 levels were generated by lentiviral transduction.

β-Lactam synthon-interceded diastereoselective synthesis of functionalized octahydroindole-based molecular scaffolds and their in vitro cytotoxic evaluation.

A convenient and unprecedented synthesis of functionally enriched octahydroindole-based scaffolds has been developed via inter- and intra-molecular amidolysis of C-3 functionalized β-lactams. The cytotoxic evaluation on oesophageal cancer cell line WHCO1 has revealed 7d as the most potent of the test compounds exhibiting an IC(50) value of 12.97 μM.

1,4-Bis[(2-pyridyl-eth-yl)imino-meth-yl]benzene.

In the title compound, C(22)H(22)N(4), the centroid of the benzene ring is located on an inversion centre. The dihedral angle between the benzene and pyridine rings is 10.94 (5)°.

Clinical significance of serum expression of GROβ in esophageal squamous cell carcinoma.

Aim: To determine the association between serum levels of growth-related gene product β (GROβ) and clinical parameters in esophageal squamous cell carcinoma (ESCC).

Methods: Using enzyme-linked immunosorbent assay, serum GROβ levels were measured in ESCC patients (n = 72) and healthy volunteers (n = 83). The association between serum levels of GROβ and clinical parameters of ESCC was analyzed statistically.

Identification and in vitro anti-esophageal cancer activity of a series of halogenated monoterpenes isolated from the South African seaweeds Plocamium suhrii and Plocamium cornutum.

Five known (1, 2, 4, 6 and 7) halogenated monoterpenes together with 1Z,3R∗,4S∗,5E,7Z)-1-bromo-3,4,8-trichloro-7-(dichloromethyl)-3-methylocta-1,5,7-triene (3) and (3R∗,4S∗)-3,4,6,7-tetrachloro-3,7-dimethyl-octen-1-ene (5) were isolated from the red macroalga Plocamium suhrii and their structures deduced from their spectroscopic data. The seven compounds from P. suhrii together with five related compounds from Plocamium cornutum have been evaluated for their cytotoxic effects on an esophageal cancer cell line (WHCO1).

GROβ and its downstream effector EGR1 regulate cisplatin-induced apoptosis in WHCO1 cells.

Cisplatin is one of the most widely used chemotherapeutic agents employed for treatment of a wide variety of solid tumors, including human esophageal squamous cell carcinoma (ESCC). However, a major limitation of cisplatin-based chemotherapy of ESCC is the rather low-effective rate. Understanding the molecular events of limited efficacy of cisplatin-based chemotherapy of ESCC could lead to strategies resulting in improved therapeutic benefits.

A key role for early growth response-1 and nuclear factor-kappaB in mediating and maintaining GRO/CXCR2 proliferative signaling in esophageal cancer.

Although early growth response-1 (EGR-1) has been shown as a key transcription factor in controlling cell growth, proliferation, differentiation, and angiogenesis, its role in the development of esophageal cancer is poorly understood despite the high frequency of this disease in many parts of the world. Here, immunohistochemistry showed that EGR-1 is overexpressed in 80% of esophageal tumor tissues examined. Furthermore, EGR-1 is constitutively expressed in all esophageal cancer cell lines analyzed.

The Karyopherin proteins, Crm1 and Karyopherin beta1, are overexpressed in cervical cancer and are critical for cancer cell survival and proliferation.

The Karyopherin proteins are involved in nucleo-cytoplasmic trafficking and are critical for protein and RNA subcellular localization. Recent studies suggest they are important in nuclear envelope component assembly, mitosis and replication. Since these are all critical cellular functions, alterations in the expression of the Karyopherins may have an impact on the biology of cancer cells.

Associations between p53 overexpression and multiple measures of clinical outcome in high-risk, early stage or suboptimally-resected, advanced stage epithelial ovarian cancers A Gynecologic Oncology Group study.

Objective: The Gynecologic Oncology Group (GOG) performed a detailed analysis of p53 overexpression in previously-untreated women with invasive early or advanced stage epithelial ovarian cancer (EOC).

Methods: Women were eligible for the study if they provided a tumor block for translational research and participated in either GOG-157, a randomized phase III trial of three versus (vs.) six cycles of paclitaxel+carboplatin in high-risk, early stage EOC, or GOG-111, a randomized phase III trial of cyclophosphamide+cisplatin vs.

Bioactive metabolites from the South African marine mollusk Trimusculus costatus.

A reinvestigation of extracts of the endemic South African intertidal limpet Trimusculus costatus yielded the known labdane diterpenes 6beta,7alpha-diacetoxylabda-8,13 E-dien-15-ol ( 1) and 2alpha,6beta,7alpha-triacetoxylabda-8,13 E-dien-15-ol ( 2) and three new metabolites, 6beta,7alpha,15-triacetoxylabda-8,13 E-diene ( 3), 3alpha,11-dihydroxy-9,11-seco-cholest-4,7-dien-6,9-dione ( 4), and cholest-7-en-3,5,7-triol ( 5). Chiral derivatization and X-ray analysis were used to confirm the labdane absolute configuration of 2. Compounds 1, 2 and 4 exhibited moderate activity (3-25 microM) against the WHCO1 human esophageal cancer cell line.

Reactive oxygen species mediated apoptosis of esophageal cancer cells induced by marine triprenyl toluquinones and toluhydroquinones.

Marine invertebrates, algae, and microorganisms are prolific producers of novel secondary metabolites. Some of these secondary metabolites have the potential to be developed as chemotherapeutic agents for the treatment of a wide variety of diseases, including cancer. We describe here the mechanism leading to apoptosis of esophageal cancer cell lines in the presence of triprenylated toluquinones and toluhydroquinones originally isolated from the Arminacean nudibranch Leminda millecra.

Halogenated monoterpene aldehydes from the South African marine alga Plocamium corallorhiza.

Four new halogenated monoterpene aldehydes (1-4) have been isolated from the South African marine red alga Plocamium corallorhiza, along with the known compounds 4,6-dibromo-1,1-dichloro-3,7-dimethyl-2E,7-octadiene (5) and 1,4,8-tribromo-3,7-dichloro-3,7-dimethyl-1E,5E-octadiene (10). The structures of the new compounds were determined by interpretation of their spectroscopic data and synthesis and mass spectrometric analysis of their pentafluorobenzyloxime (PFBO) derivatives.

A growth-related oncogene/CXC chemokine receptor 2 autocrine loop contributes to cellular proliferation in esophageal cancer.

Growth-related oncogene (GRO), a member of the CXC chemokine subfamily, plays a major role in inflammation and wound healing. CXC chemokines have been found to be associated with tumorigenesis, angiogenesis, and metastasis. Although elevated expression of GRO has been reported in several human cancers, the expression and role of GRO and its receptor, CXCR2, in esophageal cancer are poorly understood.

Antiesophageal cancer activity from Southern African marine organisms.

Squamous cell esophageal cancer presents a significant health burden in many developing countries around the world. In South Africa, this disease is one of the most common causes of cancer-related deaths in black males. Because this cancer is only modestly responsive to available chemotherapeutic agents, there is a need to develop more effective therapeutic agents for this cancer.

Plocoralides A-C, polyhalogenated monoterpenes from the marine alga Plocamium corallorhiza.

Three new polyhalogenated monoterpenes, plocoralides A-C (1-3) along with three known compounds (4-6) have been isolated from the organic extract of the red alga P. corallorhiza. Structures of the new compounds were characterized as 4,8-dibromo-1,1-dichloro-3,7-dimethyl-2E,6E-octadiene (1), 4,6-dibromo-1,1-dichloro-3,7-dimethyl-2E,7-octadiene (2) and 4,8-dibromo-1,1,7-trichloro-3,7-dimethyl-2E,5Z-octadiene (3) on the basis of one- and two-dimensional NMR spectroscopic data and MS analyses.

Makaluvic acids from the South African latrunculid sponge Strongylodesma aliwaliensis.

Two new metabolites, makaluvic acid C (1) and N-1-beta-d-ribofuranosylmakaluvic acid C (2), were isolated from the recently described sponge Strongylodesma aliwaliensis collected off the east coast of South Africa. Standard spectroscopic techniques provided the structures of both compounds. Chiral GC analysis of the peracetylated aldononitrile derivative of the acid hydrolysate of 2 confirmed the d-configuration of the ribose moiety in this compound.