Inhibitors of apoptosis proteins in prostate cancer cell lines

BACKGROUND: The caspases are the central executioners of apoptosis. The inhibitors of apoptosis proteins (IAPs) are a family of recently described caspase inhibitors. We hypothesised that tumor resistance to apoptosis could be due in part to IAP expression. METHODS: The expression of NAIP, cIAP-1, cIAP-2, XIAP, and survivin was investigated in the prostate cancer cell lines LNCaP, PC3, and DU145. RNase protection assays and Western blotting were used to assess RNA and protein expression. Apoptotic susceptibility was determined using etoposide and assessed by propidium iodide (PI) DNA incorporation using flow cytometry. RESULTS: DU145 and PC3 cells were more resistant to apoptosis than LNCaP cells. All the IAPs were identified in the cell lines with variation in IAP expression between different cell types. Immunohistochemistry demonstrated cIAP-1 expression in PC3 cells was nuclear, while the expression of cIAP-2 and XIAP was perinuclear. Growing LNCaP cells in charcoal-stripped or androgen-supplemented medium resulted in no alteration in IAP expression. CONCLUSIONS: This study characterises the expression of IAP in three of the most commonly used prostate cancer cells. IAP may make an important contribution to apoptotic resistance in patients with prostate cancer.     

Tumour localisation with a metal coil before the administration of neo-adjuvant chemotherapy

Complete clinical response (CR) with tumour disappearance is not uncommon after neo-adjuvant chemotherapy (NAC) for locally advanced breast cancer, avoiding 25% mastectomies by facilitating breast-conserving procedures. We reviewed our series to understand the feasibility and utility of marking the cancer site before administering NAC. In total, 23 women (median age 47 years) with T2-4, N0-1, M0 tumours were considered unsuitable for breast conserving surgery between January 2002 and November 2003, thus received NAC following a coil placement at the core of tumour. All patients had the coil successfully inserted and no migration or infection was recorded. Eight patients (35%) had a radiological CR (rCR) including 3 (13%) with pathological CR (pCR). In total, 87% patients were managed conservatively. The insertion of a metal coil is a simple mean to provide a landmark for localisation and excision when the breast lump becomes impalpable and radiologically undetectable after the administration of NAC.     

A case report of tumor lysis syndrome after stage-one ALPPS

Rationale:Tumor lysis syndrome is a potentially lethal condition caused by rapid cell death, releasing a high level of toxic cytokines. It is common in patients with hematological malignancy but rare in solid tumors.Patient concerns:A 64-year-old patient presented to our unit with a 17.3-cm hepatocellular carcinoma and marginal liver reserve. The first-stage operation of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) was performed.Diagnosis:The patient was found to be anuric with grossly deranged electrolytes after the first-stage operation. Tumor lysis syndrome was diagnosed.Interventions:The patient was transferred to the intensive care unit for aggressive fluid administration and continuous venovenous hemofiltration for the management of tumor lysis syndrome.Outcomes:The patient recovered and then underwent the second-stage operation of ALPPS with extended right hepatectomy 8 days after the initial operation without any long-term sequelae.Lessons:ALPPS is a relatively new technique in liver surgery, entailing an increased risk of tumor lysis syndrome due to an in situ tumor after the first-stage operation. Clinicians should have a high index of suspicion regarding this potentially lethal complication with prompt management.     

Assessment of the genotoxic and carcinogenic potentials of 3‐aminothiophene derivatives using in vitro and in silico methodologies

Thiophene derivatives, a class of compounds widely used in products such as pharmaceuticals, agrochemicals or dyestuffs, represent chemicals of concern. Indeed, the thiophene ring is often considered as a structural moiety that may be involved in toxic effects in humans. We primarily focus on the genotoxic/mutagenic and carcinogenic potentials of the methyl 3‐amino‐4‐methylthiophene‐2‐carboxylate (1), a precursor of the articaine local anesthetic (4) which falls within the scope of the European REACH (Registration, Evaluation, Authorisation and restriction of CHemicals) legislation. To discern some structure–toxicity relationships, we also studied two related compounds, namely the 3‐amino 4‐methylthiophene (2) and the 2‐acetyl 4‐chlorothiophene (3). Techniques employed to assess mutagenic and DNA‐damaging effects involved the Salmonella mutagenicity assay (or Ames test) and the single‐cell gel electrophoresis assay (or Comet assay). In the range of tested doses, none of these derivatives led to a positive response in the Ames tests and DNA damage was only observed in the Comet assay after high concentration exposure of 2. The study of their carcinogenic potential using the in vitro SHE (Syrian Hamster Embryo) cell transformation assay (CTA) highlighted the activity of compound 2. A combination of experimental data with in silico predictions of the reactivity of thiophene derivatives towards cytochrome P450 (CYP450), enabled us to hypothesize possible pathways leading to these toxicological profiles. Copyright © 2013 John Wiley & Sons, Ltd.     

Ultrastructural study of exclamation-mark hair shafts in alopecia areata

The prime diagnostic feature of acute alopecia areata is the presence of exclamation mark hairs. These characteristic hairs fracture at their distal end and taper proximally towards the scalp, giving them the appearance of an exclamation mark. Hair morphology was studied in 8 patients with untreated acute alopecia areata and 3 normal adults without hair loss. Light microscopy, transmission and scanning electron microscopy revealed distinct structural differences in the distal end of hairs compared with the remainder of their length and with normal hair shafts. Transverse sections of hairs just below the frayed brush-like tip often displayed asymmetrical cortex disintegration. One side was compact and homogeneous while the other was deeply fissured and/or broken up into discrete heterogeneous-staining fragments of cortical, stratum corneum and cuticular components in addition to apparently degenerate cortex. Many exclamation mark hair tips lacked cuticle and had irregular profiles. Melanin was found in cortical and medullary fragments at the tip, although it was absent in the more degenerate forms of cortex. More proximal sections of these pathognomic telogen hairs revealed nearly normal hair shaft ultrastructure.