Nutrients and phytoplankton dynamics in the fishing grounds off Tiruchendur coastal waters, Gulf of Mannar, India.

Nutrients and phytoplankton dynamics in the traditional fishing grounds off Tiruchendur coast, Gulf of Mannar, India revealed a clear seasonal trend influenced by prevailing monsoon system in east coast of India. A total of 73 species of phytoplankton were identified from the fishing grounds, revealed higher abundance in summer months compared to other seasons. Among the three stations, maximum phytoplankton abundance was recorded in station 2 followed by stations 1 and 3. The phytoplankton abundance ranged from 2.85 × 10(4) to 6.34 × 10(4) cells/l, with higher and lower value observed during summer and post monsoon season respectively. Chl-a showed similar seasonal trend with phytoplankton abundance and fluctuated from 0.4 to 6.8 mg/m(3) with high concentrates were recorded during summer. Primary productivity was ranged from 13.8 to 28.7 mg, C/m(2)/day with maximum and minimum during summer and monsoon respectively. It was understood from the study, ammonia could be acting as the limiting nutrient for phytoplankton growth, while the role of nitrate, nitrite, phosphate and silicate remained insignificant. At the time of diatom population proliferates there was a drop in the nutrient levels was observed during the study. The water current flowing from north to south during the northeast monsoon, nutrient rich fresh water discharged from Tamirabarani River influencing the nutrient dynamics in the fishing grounds that are ultimately increasing the nutrients concentration during northeast monsoon.

Effect of denosumab versus zoledronic acid in preventing skeletal-related events in patients with bone metastases by baseline characteristics.

BACKGROUND: Analyses of phase III trials showed that denosumab was superior to zoledronic acid (ZA) in preventing skeletal-related events (SREs) irrespective of age, history of SREs, or baseline pain status. This analysis assessed the risk of SREs across additional baseline characteristics. PATIENTS AND METHODS: Patients (N = 5543) from three phase III trials who had breast cancer, prostate cancer, or other solid tumours and one or more bone metastasis were included. Superiority of denosumab versus ZA in reducing risk of first SRE and first and subsequent SREs was assessed in subgroups defined by the Eastern Cooperative Oncology Group performance status (ECOG PS), bone metastasis location, bone metastasis number, visceral metastasis presence/absence, and urinary N-telopeptide (uNTx) level using Cox proportional hazards and Anderson-Gill models. Subgroups except bone metastasis location were also assessed for each solid tumour type. RESULTS: Compared with ZA, denosumab significantly reduced the risk of first SRE across all subgroups (hazard ratio [HR] ranges: ECOG PS, 0.79-0.84; bone metastasis location, 0.78-0.83; bone metastasis number, 0.78-0.84; visceral metastasis presence/absence, 0.80-0.82; uNTx level, 0.73-0.86) and reduced the risk of first and subsequent SREs in all subgroups (HR ranges: ECOG PS, 0.76-0.83; bone metastasis location, 0.78-0.84; bone metastasis number, 0.79-0.81; visceral metastasis presence/absence, 0.79-0.81; uNTx level, 0.74-0.83). Similar results were observed in subgroups across tumour types. CONCLUSION: Denosumab was superior to ZA in preventing SREs in patients with bone metastases from advanced cancer, regardless of ECOG PS, bone metastasis number, baseline visceral metastasis presence/absence, and uNTx level.

Elevation in multiple serum inflammatory biomarkers predicts survival of pancreatic cancer patients with inoperable disease.

PURPOSE: Cancer-associated inflammation plays a driver role in pancreatic tumor development and progression. Moreover, recent studies have implicated the inflammatory tumor microenvironment in modulating therapy response and inducing resistance. The aim of this study is to investigate the prognostic and predictive value of the inflammatory biomarkers serum ferritin and C-reactive protein (CRP) in advanced pancreatic cancer patients. METHODS: We measured pretreatment serum ferritin and CRP levels in 159 patients with inoperable pancreatic cancer participating in a phase III trial. RESULTS: Serum ferritin and CRP levels were examined for correlations with overall survival using Kaplan-Meier analysis. When analyzed on a categorical basis, patients with higher ferritin (>median) or CRP (>25th percentile) had shorter overall survival. Moreover, the two biomarkers were not correlated suggesting independent mechanisms of production and release. However, when patients were evaluated by their ferritin and CRP levels, only patients with elevation in both inflammatory biomarkers showed a significant decrease in overall survival. CONCLUSIONS: Serum ferritin and CRP are independent prognostic factors for shorter survival in patients with inoperable pancreatic tumors. Moreover, the evaluation of patients based on both biomarkers suggested that their prognostic value, although independent, reflected the broader state of cancer-associated inflammation. Thus, serum ferritin and CRP should be further explored as clinical biomarkers.

RANKL enhances the effect of an antagonist of inhibitor of apoptosis proteins (cIAPs) in RANK-positive breast cancer cells.

OBJECTIVE: Between 65% and 75% of patients with metastatic breast cancer will have decreased 5-year survival and increased morbidity due to cancer relapse in bone. At this stage of disease treatment is palliative, but tumor-targeted compounds could add to the benefits of anti-resorptive agents, improving clinical outcome. Inhibitor-of-apoptosis proteins (IAPs) are overexpressed in many tumors and second mitochondria-derived activator of caspases (Smac) mimetics have been designed to antagonize IAPs. In this work we explored the use of AT-406, a Smac mimetic, to target the tumor compartment of bone metastases. METHODS: Effect of AT-406 on cancer cells apoptosis, expression of IAPs and osteogenic potential was addressed in vitro using the RANK-positive MDA-MB-231 breast cancer cell line. Effect of AT-406 on osteoclastogenesis was determined by inducing the differentiation of the RAW 264.7 mouse monocytic cell line. Osteoclastogenesis was measured by TRAP staining and TRACP 5b quantification. RESULTS: AT-406 increased apoptosis in MDA-MB-231 breast cancer cells in vitro, and activation of RANK-pathway improved this effect. RANKL stimuli induced a strong increase in c-IAP2. AT-406 increased osteoclast differentiation and activity, by up-regulating the osteogenic transcription factor Nfatc1, but also increased the apoptosis of mature osteoclasts in the absence of RANKL. CONCLUSIONS: Our results indicate that despite the anti-tumoral effect of AT-406, its use in the context of bone metastatic disease needs to be carefully monitored for the induction of increased bone resorption. We also hypothesize that the combination of AT-406 with anti-RANKL directed therapies could have a beneficial effect, especially in RANK-positive tumors.

Skeletal-related events and clinical outcomes in patients with bone metastases and normal levels of osteolysis: exploratory analyses.

AIMS: High levels of bone resorption markers (e.g. N-telopeptide of type I collagen; NTX) have been correlated with increased risks of skeletal-related events and death in patients with bone metastases from solid tumours. However, the disease course has not been well characterised in patients with bone metastases but normal NTX levels. Therefore, the aim of this study was to evaluate the patterns of skeletal morbidity in patients with normal NTX levels. MATERIALS AND METHODS: Exploratory analyses were carried out on patients with bone metastases from breast cancer, castration-resistant prostate cancer, non-small cell lung cancer or other solid tumours treated with zoledronic acid (ZOL) in phase III trials. The effects of covariates on the relative risk of death were estimated using the Cox proportional hazard model. The prognostic values of covariates were compared between patients with normal (<64 nmol/mmol creatinine) versus elevated (≥64 nmol/mmol creatinine) NTX levels. RESULTS: Among patients with normal baseline NTX (n = 501), less than 10% developed elevated NTX levels before a skeletal-related event or death during ZOL treatment over 12 months. The prognostic factors identified in these analyses were mostly similar across NTX groups. However, some indicators of aggressive disease (e.g. visceral/cerebral metastases from breast cancer) were associated with poor clinical outcomes only in the normal NTX group. CONCLUSIONS: Skeletal-related events were generally not preceded or followed by transition to elevated NTX in patients treated with ZOL. Elevated baseline NTX and aggressive extraskeletal disease were independently associated with reduced survival.

Isolation of a bacteriocin-producing lactococcus lactis and application of its bacteriocin to manage spoilage bacteria in high-value marine fish under different storage temperatures.

The bacteriocins of lactic acid bacteria have considerable potential for biopreservation. The Lactococcus lactis strain PSY2 (GenBank account no. JF703669) isolated from the surface of marine perch Perca flavescens produced antibacterial activity against pathogenic and spoilage-causing Gram-positive and Gram-negative bacteria viz. Arthrobacter sp., Acinetobacter sp., Bacillus subtilis, Escherichia coli, Listeria monocytogenes, Pseudomonas aeruginosa and Staphylococcus aureus and possessed broad inhibitory spectrum. The biopreservative efficacy of the bacteriocin PSY2 was evaluated using fillets of reef cod, Epinephelus diacanthus. The fillets (10 g) were sprayed with 2.0 ml of 1,600 AU/ml bacteriocin, wrapped and kept under different storage temperatures viz., 4, 0 and -18 °C. The biopreservative extended the shelf-life of fillets stored at 4 °C to >21 days as against <14 days observed in the untreated samples. The total count of spoilage bacteria was reduced by 2.5 logarithmic units in the treated sample during the 14th day of storage as against the control. Chemical analysis revealed a significant change (P < 0.05) in the pH value, free fatty acid (as % oleic acid), total volatile base nitrogen and total methyl amine content in the treated samples. The overall acceptability in terms of sensory attributes was significantly higher in the bacteriocin-treated samples stored for 21 days at 4 °C while the untreated samples became unacceptable by the 14th day. The biopreservative gave no significant effect at -18 °C. Thus, the bacteriocin derived from L. lactis PSY2 gave increased protection against spoilage bacteria and offers an alternative for the preservation of high-value sea foods.

Cancer treatment-induced bone loss in premenopausal women: a need for therapeutic intervention?

Current clinical treatment guidelines recommend cytotoxic chemotherapy, endocrine therapy, or both (with targeted therapy if indicated) for premenopausal women with early-stage breast cancer, depending on the biologic characteristics of the primary tumor. Some of these therapies can induce premature menopause or are specifically designed to suppress ovarian function and reduce circulating estrogen levels. In addition to bone loss associated with low estrogen levels, cytotoxic chemotherapy may have a direct negative effect on bone metabolism. As a result, cancer treatment-induced bone loss poses a significant threat to bone health in premenopausal women with breast cancer. Clinical trials of antiresorptive therapies, such as bisphosphonates, have demonstrated the ability to slow or prevent bone loss in this setting. Current fracture risk assessment tools are based on data from healthy postmenopausal women and do not adequately address the risks associated with breast cancer therapy, especially in younger premenopausal women. We therefore recommend that all premenopausal women with breast cancer be informed about the potential risk of bone loss prior to beginning anticancer therapy. Women who experience amenorrhea should have bone mineral density assessed by dual-energy X-ray absorptiometry and receive regular follow-up to monitor bone health. Regular exercise and daily calcium and vitamin D supplementation are recommended. Women with a Z-score <-2.0 or Z-score ≤-1.0 and/or a 5-10% annual decrease in bone mineral density should be considered for bisphosphonate therapy in addition to calcium and vitamin D supplements.

Management of aromatase inhibitor-associated bone loss in postmenopausal women with breast cancer: practical guidance for prevention and treatment.

BACKGROUND: Bone mineral density (BMD)-based guidelines for bone-directed therapy in women with early breast cancer (EBC) appear inadequate for averting fractures, particularly during aromatase inhibitor (AI) therapy. Therefore, an algorithm was developed to better assess risk and direct treatment (Hadji P, Body JJ, Aapro MS et al. Practical guidance for the management of aromatase inhibitor-associated bone loss. Ann Oncol 2008; 19: 1407-1416). Here, we provide updated guidance on pharmacologic interventions to prevent/treat aromatase inhibitor-associated bone loss (AIBL). DESIGN: Systematic literature review identified recent advances in preventing/treating AIBL. Individual agents were assessed based on trial size, design, follow-up, and safety. RESULTS: Fracture risk factors in patients with EBC remain unchanged (Hadji P, Body JJ, Aapro MS et al. Practical guidance for the management of aromatase inhibitor-associated bone loss. Ann Oncol 2008; 19: 1407-1416). The World Health Organization Fracture Risk Assessment Tool algorithm includes fracture risk factors plus BMD but does not adequately address AIBL effects. Several antiresorptives can prevent/treat AIBL. However, concerns regarding compliance and long-term efficacy/safety remain. Overall, evidence is strongest for twice-yearly zoledronic acid (ZOL), and recent advances support additional anticancer benefits from ZOL. CONCLUSIONS: All patients initiating AIs need advice regarding exercise, calcium/vitamin D supplements, baseline BMD monitoring (when available), and bone-directed therapy if T-score <-2.0 or at least two fracture risk factors were observed. Patients with T-score > -2.0 and no risk factors should be managed based on BMD loss during years 1-2. Unsatisfactory compliance/decreasing BMD after 12-24 months on oral bisphosphonates should trigger a switch to i.v. bisphosphonate.

Identification of a subpopulation of metastatic breast cancer patients with very high HER2 expression levels and possible resistance to trastuzumab.

BACKGROUND: Patients with metastatic breast cancer (MBC) overexpressing HER2 (human epidermal growth factor receptor 2) are currently selected for treatment with trastuzumab, but not all patients respond. PATIENTS AND METHODS: Using a novel assay, HER2 protein expression (H2T) was measured in formalin-fixed, paraffin-embedded primary breast tumors from 98 women treated with trastuzumab-based therapy for MBC. Using subpopulation treatment effect pattern plots, the population was divided into H2T low (H2T < 13.8), H2T high (H2T ≥ 68.5), and H2T intermediate (13.8 ≤ H2T < 68.5) subgroups. Kaplan-Meier (KM) analyses were carried out comparing the groups for time to progression (TTP) and overall survival (OS). Cox multivariate analyses were carried out to identify correlates of clinical outcome. Bootstrapping analyses were carried out to test the robustness of the results. RESULTS: TTP improved with increasing H2T until, at the highest levels of H2T, an abrupt decrease in the TTP was observed. KM analyses demonstrated that patients with H2T low tumors [median TTP 4.2 months, hazard ratio (HR) = 3.7, P < 0.0001] or H2T high tumors (median TTP 4.6 months, HR = 2.7, P = 0.008) had significantly shorter TTP than patients whose tumors were H2T intermediate (median TTP 12 months). OS analyses yielded similar results. CONCLUSIONS: MBC patients with very high levels of H2T may represent a subgroup with de novo resistance to trastuzumab. These results are preliminary and require confirmation in larger controlled clinical cohorts.

The insulin-like growth factor-I receptor inhibitor figitumumab (CP-751,871) in combination with docetaxel in patients with advanced solid tumours: results of a phase Ib dose-escalation, open-label study.

BACKGROUND: This phase Ib trial assessed safety, tolerability, and maximum tolerated dose (MTD) of figitumumab (CP-751,871), a fully human monoclonal antibody targeting the insulin-like growth factor type 1 receptor (IGF-IR), in combination with docetaxel. METHODS: Patients with advanced solid tumours were treated with escalating dose levels of figitumumab plus 75 mg m(-2) docetaxel every 21 days. Safety, efficacy, pharmacokinetics (PKs), and biomarker responses were evaluated. RESULTS: In 46 patients, no dose-limiting toxicities were attributable to the treatment combination. Grade 3 and 4 toxicities included neutropaenia (n=28), febrile neutropaenia (n=11), fatigue (n=10), leukopaenia (n=7), diarrhoea (n=5), hyperglycaemia, lymphopaenia, cellulitis, DVT, and pain (all n=1). The MTD was not reached. Four partial responses were observed; 12 patients had disease stabilisation of > or =6 months. Pharmacokinetic and biomarker analyses showed a dose-dependent increase in plasma exposure, and complete sIGF-IR downregulation at doses of >or =3 mg kg(-1). Pharmacokinetics of docetaxel in combination was similar to when given alone. Out of 18 castration-resistant prostate cancer patients, 10 (56%) had > or =5 circulating tumour cells (CTCs) per 7.5 ml of blood at baseline: 6 out of 10 (60%) had a decline from > or =5 to <5 CTCs and 9 out of 10 (90%) had a > or =30% decline in CTCs after therapy. CONCLUSIONS: Figitumumab and docetaxel in combination are well tolerated. Further evaluation is warranted.

Prognostic variables for survival and skeletal complications in patients with multiple myeloma osteolytic bone disease.

Skeletal-related events (SREs) are common in patients with osteolytic lesions from multiple myeloma (MM), and result in substantial morbidity. We report herein a comprehensive, retrospective, multivariate analysis of prognostic factors for survival and first on-study SRE in MM patients using data from the phase III, randomized study comparing zoledronic acid with pamidronate in MM or breast cancer. Cox regression analyses were used to assess 22 variables for prognostic significance (defined as associations with P<0.05) in patients with bone metabolism marker assessments and complete baseline variable data. Of 510 evaluable MM patients, 282 had complete covariate information and were included in models. Reduced Cox multivariate models identified five significant prognostic factors for first SRE (weight, race, high N-terminal cross-linked telopeptide of type I collagen (NTX), high pain score, and need for narcotic analgesics) and seven for survival (age, SRE history, myeloma subtype, anemia, high lactate dehydrogenase, high NTX, and low albumin levels). High NTX was the only variable associated with elevated risks of both first SRE and death (P< or =0.02 for each). These analyses identified prognostic factors for SREs and survival in patients with MM. Taken together with current staging systems, these factors could further facilitate decision making for optimal treatment of myeloma bone disease, although further prospective assessments are needed.

Guaiane sesquiterpenes from seaweed Ulva fasciata Delile and their antibacterial properties.

Two new guaiane sesquiterpene derivatives, guai-2-en-10alpha-ol (1) and guai-2-en-10alpha-methanol (2), were chromatographically purified as major constituents of the CHCl3/CH3OH (1:1, v/v) soluble fraction of Ulva fasciata. Acetylation of 2 furnished guai-2-en-10alpha-methyl methanoate (3) with acetyl group at C11 position. The structures of the compounds were elucidated using one and two-dimensional NMR and mass spectrometric analysis. Compounds 2 and 3 exhibited significant inhibition to the growth of Vibrio parahaemolyticus with minimum inhibitory concentrations of 25 and 35 microg/mL, respectively. The electronegative C10 acetyl group with high polarisability (7.02x10(-24) cm3) in 3 appeared to withdraw electron cloud from substituted cycloheptyl ring and (R)-3-methylcyclohept-1-ene moiety, thus acting as the nucleophilic center of the molecule resulting in high bioactivity.

Sponge-microbial interactions: Ecological implications and bioprospecting avenues.

Sponges are closely associated with microorganisms that occur either intracellularly and extracellularly. Sponges are soft-bodied sessile organisms appear to be defenseless in facing predation. Microbial symbionts supposed to have a functional role in the host defense against pathogens, predation and microfouling processes. Recently, the ubiquitous defense enzyme, phospholipase A2 (PLA2) detected in the sponge associated bacterium envisaged the possible functional role in the ecological succession of host sponge against predatory / fouling pressure in the habitat. In present review, we highlighted the possible functional interactions between associated microbes and host sponges and its potentials in bioprospecting approaches.

Elevated plasma endoglin (CD105) predicts decreased response and survival in a metastatic breast cancer trial of hormone therapy.

Background Endoglin (CD105) is a co-receptor for TGF-beta, is expressed by human vascular endothelial cells, and plays a major role in angiogenesis. Materials and methods Pretreatment EDTA plasma from 224 metastatic breast cancer patients enrolled in a phase III 2nd-line hormone therapy trial and 50 control subjects were assayed for endoglin using an ELISA. Results The female control group (n = 50) plasma endoglin upper limit of normal was defined as the mean + 2 SD (8.7 ng/ml). The breast cancer patient plasma endoglin was 6.40 +/- 2.23 ng/ml (range 3.00-19.79 ng/ml). Elevated plasma endoglin levels were detected in 26 of 224 patients (11.6%). Patients with elevated plasma endoglin had a reduced clinical benefit rate (CR + PR + Stable) (15 vs. 42%) (P = 0.01) to hormone therapy. TTP was shorter for patients with elevated plasma endoglin, but did not reach statistical significance (P = 0.2). Patients with elevated plasma endoglin had decreased overall survival (median 645 vs. 947 days) (P = 0.005). Conclusion Elevated pretreatment plasma endoglin levels predicted for decreased clinical benefit and a shorter overall survival in metastatic breast cancer patients treated with 2nd-line hormone therapy.

Optimization and characterization of a new lipopeptide biosurfactant produced by marine Brevibacterium aureum MSA13 in solid state culture.

The biosurfactant production of a marine actinobacterium Brevibacterium aureum MSA13 was optimized using industrial and agro-industrial solid waste residues as substrates in solid state culture (SSC). Based on the optimization experiments, the biosurfactant production by MSA13 was increased to threefold over the original isolate under SSC conditions with pre-treated molasses as substrate and olive oil, acrylamide, FeCl(3) and inoculums size as critical control factors. The strain B. aureum MSA13 produced a new lipopeptide biosurfactant with a hydrophobic moiety of octadecanoic acid methyl ester and a peptide part predicted as a short sequence of four amino acids including pro-leu-gly-gly. The biosurfactant produced by the marine actinobacterium MSA13 can be used for the microbially enhanced oil recovery processes in the marine environments.

Characterization of Mg2+ binding to the DNA repair protein apurinic/apyrimidic endonuclease 1 via solid-state 25Mg NMR spectroscopy.

Apurinic/apyrimidinic endonuclease 1 (APE1), a member of the divalent cation-dependent phosphoesterase superfamily of proteins that retain the conserved four-layered alpha/beta-sandwich structural core, is an essential protein that functions as part of base excision repair to remove mutagenic and cytotoxic abasic sites from DNA. Using low-temperature solid-state (25)Mg NMR spectroscopy and various mutants of APE1, we demonstrate that Mg(2+) binds to APE1 and a functional APE1-substrate DNA complex with an overall stoichiometry of one Mg(2+) per mole of APE1 as predicted by the X-ray work of Tainer and co-workers (Mol, C. D.; Kuo, C. F.; Thayer, M. M.; Cunningham, R. P.; Tainer, J. A. Nature 1995, 374 , 381-386). However, the NMR spectra show that the single Mg(2+) site is disordered. We discuss the probable reasons for the disorder at the Mg(2+) binding site. The most likely source of this disorder is arrangement of the protein-ligands about the Mg(2+) (cis and trans isomers). The existence of these isomers reinforces the notion of the plasticity of the metal binding site within APE1.

Practical guidance for the management of aromatase inhibitor-associated bone loss.

BACKGROUND: Recent studies indicate that women with breast cancer are at increased risk of fracture compared with their age-matched peers. Current treatment guidelines are inadequate for averting fractures in osteopenic women, especially those receiving aromatase inhibitor (AI) therapy. Therefore, we sought to identify clinically relevant risk factors for fracture that can be used to assess overall fracture risk and to provide practical guidance for preventing and treating bone loss in women with breast cancer receiving AI therapy. METHODS: Systematic review of pertinent information from published literature and meeting abstracts through December 2007 was carried out to identify factors contributing to fracture risk in women with breast cancer. An evidence-based medicine approach was used to select risk factors that can be used to determine when to initiate bisphosphonate treatment of aromatase inhibitor-associated bone loss (AIBL). RESULTS: Fracture risk factors were chosen from large, well-designed, controlled, population-based trials in postmenopausal women. Evidence from multiple prospective clinical trials in women with breast cancer was used to validate AI therapy as a fracture risk factor. Overall, eight fracture risk factors were validated in women with breast cancer: AI therapy, T-score <-1.5, age >65 years, low body mass index (BMI <20 kg/m(2)), family history of hip fracture, personal history of fragility fracture after age 50, oral corticosteroid use >6 months, and smoking. Treatment recommendations were derived from randomized clinical trials. CONCLUSIONS: The authors recommend the following for preventing and treating AIBL in women with breast cancer. All patients initiating AI therapy should receive calcium and vitamin D supplements. Any patient initiating or receiving AI therapy with a T-score >/=-2.0 and no additional risk factors should be monitored every 1-2 years for change in risk status and bone mineral density (BMD). Any patient initiating or receiving AI therapy with a T-score <-2.0 should receive bisphosphonate therapy. Any patient initiating or receiving AI therapy with any two of the following risk factors-T-score <-1.5, age >65 years, low BMI (<20 kg/m(2)), family history of hip fracture, personal history of fragility fracture after age 50, oral corticosteroid use >6 months, and smoking-should receive bisphosphonate therapy. BMD should be monitored every 2 years, and treatment should continue for at least 2 years and possibly for as long as AI therapy is continued. To date, the overwhelming majority of clinical evidence supports zoledronic acid 4 mg every 6 months to prevent bone loss in women at high risk. Although there is a trend towards fewer fractures with zoledronic acid, studies completed to date have not been designed to capture significant differences in fracture rate, and longer follow-up is needed.

Guidance on the use of bisphosphonates in solid tumours: recommendations of an international expert panel.

Bisphosphonates (BP) prevent, reduce, and delay cancer-related skeletal complications in patients, and have substantially decreased the prevalence of such events since their introduction. Today, a broad range of BP with differences in potency, efficacy, dosing, and administration as well as approved indications is available. In addition, results of clinical trials investigating the efficacy of BP in cancer treatment-induced bone loss (CTIBL) have been recently published. The purpose of this paper is to review the current evidence on the use of BP in solid tumours and provide clinical recommendations. An interdisciplinary expert panel of clinical oncologists and of specialists in metabolic bone diseases assessed the widespread evidence and information on the efficacy of BP in the metastatic and nonmetastatic setting, as well as ongoing research on the adjuvant use of BP. Based on available evidence, the panel recommends amino-bisphosphonates for patients with metastatic bone disease from breast cancer and zoledronic acid for patients with other solid tumours as primary disease. Dosing of BP should follow approved indications with adjustments if necessary. While i.v. administration is most often preferable, oral administration (clodronate, IBA) may be considered for breast cancer patients who cannot or do not need to attend regular hospital care. Early-stage cancer patients at risk of developing CTIBL should be considered for preventative BP treatment. The strongest evidence in this setting is now available for ZOL. Overall, BP are well-tolerated, and most common adverse events are influenza-like syndrome, arthralgia, and when used orally, gastrointestinal symptoms. The dose of BP may need to be adapted to renal function and initial creatinine clearance calculation is mandatory according to the panel for use of any BP. Subsequent monitoring is recommended for ZOL and PAM, as described by the regulatory authority guidelines. Patients scheduled to receive BP (mainly every 3-4 weeks i.v.) should have a dental examination and be advised on appropriate measures for reducing the risk of jaw osteonecrosis. BP are well established as supportive therapy to reduce the frequency and severity of skeletal complications in patients with bone metastases from different cancers.

Subscores of the FAB differentiate frontotemporal lobar degeneration from AD.

OBJECTIVE: To determine the clinical utility of the Frontal Assessment Battery (FAB), a short test of frontal lobe functions, in differentiating frontotemporal lobar degeneration (FTLD) from Alzheimer disease (AD). METHODS: FAB total scores and subscores for 23 subjects with FTLD and 31 subjects with AD were compared for sensitivity, specificity, and positive predictive value. Concurrent validity of the FAB with the Mini-Mental State Examination (MMSE) and other scales was also assessed. RESULTS: The FAB did not have positive predictive value for FTLD. Total FAB scores did not differ between the FTLD and AD groups. However, three subtests of the FAB (mental flexibility, motor programming, and environmental autonomy) demonstrated significant differences between the two groups. Total FAB scores correlated with scores on the MMSE, a more general test of cognition. CONCLUSION: The Frontal Assessment Battery did not discriminate subjects with frontotemporal lobar degeneration from those with Alzheimer disease, though certain subtests may be helpful in differential diagnosis.

Rate of progression differs in frontotemporal dementia and Alzheimer disease.

OBJECTIVE: To compare survival and rates of cognitive and functional decline in patients with autopsy-confirmed frontotemporal dementia (FTD) and Alzheimer disease (AD) in a large multicenter study. BACKGROUND: Despite advances in the clinical characterization of FTD, little is known about its rate of progression. Characterizing survival and rate of decline in FTD is important because it can provide prognostic guidelines and benchmarks to use in the evaluation of disease-modifying drugs. METHODS: Seventy patients with FTD and 70 patients with AD who were followed by seven Alzheimer disease research centers until confirmation of diagnosis at autopsy were matched for overall age, education, and Mini-Mental State Examination (MMSE) score at initial evaluation. Survival and rates of cognitive and functional decline were compared. RESULTS: Patients with FTD had significantly shorter survival from initial evaluation to death than patients with AD (FTD = 4.2 years, AD = 6.0 years; log-rank test = 5.17, p < 0.05), and they declined significantly faster over one year on the MMSE (mean annual rate of change: -6.7 points for FTD vs -2.3 points for AD). A significantly greater proportion of patients with FTD were impaired in basic activities of daily living (ADLs) at initial evaluation, and lost the capacity for independent or minimally-assisted ADLs over the subsequent year. CONCLUSIONS: The results are consistent with shorter survival and faster rates of cognitive and functional decline in patients with frontotemporal dementia (FTD) compared to those with Alzheimer disease (AD). This suggests that FTD follows a more malignant disease course than AD once dementia is clinically recognized.