► Toxicity and chemical composition of Minthostachys verticillata essential oil were studied. ► The main compounds were pulegone, menthone and limonene. ► The essential oil not induced cytotoxic ...effect both on Vero cell and human PBMCs. ► The oil not induced apoptosis on human PBMCs nor genotoxicity on erythrocytes of mice. ► The results suggest this species appears to be a safe therapeutic agent.
Minthostachys verticillata (peperina) is an aromatic and medicinal plant with several uses and ethnobotanical properties. Numerous studies have demonstrated that its essential oil (Mv-EO) presents antimicrobial capacity and shows immunomodulating and anti-allergic properties in human cell lines. Thus, the goal of this study was to investigate the main chemical composition, analyzed by GC–FID, and the cyto-genotoxic effects of Mv-EO, using Vero cells, human PBMCs and mice bone marrow cells. The Mv-EO was rich in pulegone 60.5% and menthone 18.2%. Our results clearly show that Mv-EO is not cyto-genotoxic in vitro nor in vivo. It not induced cytotoxic effects, as indicated by trypan blue dye exclusion and NRU assays both in Vero cells and human PBMCs. In addition, Mv-EO (100–1000μg/mL) not induced apoptotic effects on human PBMCs, as indicated by Hoechst staining and DNA fragmentation analysis by agarose gel electrophoresis. The in vivo assay showed that Mv-EO (25–500mg/kg) not increased the frequency of micronucleus in bone marrow cells of mice. Further, the ratio of polychromatic/normochromatic erythrocytes was not modified. These findings suggest that Mv-EO appears to be safe as a therapeutic agent.
Pitt-Hopkins Syndrome (PTHS) is a rare genetic disorder caused by insufficient expression of the TCF4 gene. Children with PTHS typically present with gastrointestinal disorders and early severe ...chronic constipation is frequently found (75%). Here we describe the case of a PTHS male 10-year-old patient with chronic constipation in whom Osteopathic Manipulative Treatment (OMT) resulted in improved bowel functions, as assessed by the diary, the QPGS-Form A Section C questionnaire, and the Paediatric Bristol Stool Form Scale. The authors suggested that OMT may be a valid tool to improve the defecation frequency and reduce enema administration in PTHS patients.
Central nervous system gliomas Reni, Michele; Mazza, Elena; Zanon, Silvia ...
Critical reviews in oncology/hematology,
05/2017, Letnik:
113
Journal Article
Recenzirano
Abstract Evidence-based practical guidelines on diagnosis, prognosis, and treatment on the most frequent adult brain tumours are delineated. In Europe, 27,000 new cases of malignant glial tumours and ...1000 new cases of malignant ependymal tumours are diagnosed every year. The most common glial tumours are glioblastoma multiforme and anaplastic glioma, comprising more than 50% and 10%, respectively, of the total gliomas. Prognosis of gliomas is generally poor. Environmental and genetic factors have been correlated with an increased risk of developing brain tumours. Surgical resection represents the first treatment option for all histotypes. Role and timing of radiotherapy and chemotherapy as well as treatment for recurrent/progressive disease should be based on age, performance status, histopathological diagnosis, molecular markers, and previous therapy. Impaired neurocognitive and neuropsychological function is common in long-term survivors, regardless of the histology and grade of the tumour and should be taken into account in treatment planning.
•Incidence of pancreatic cancer in patients ≥65 will increase in next years.•No phase III data are available on the chemotherapy for elderly patients with PDAC.•Existing evidence suggests a ...chemotherapy benefit in the adjuvant setting and in advanced disease.•A proper patients selection is mandatory for a successful treatment.•New variables are emerging toward a tailored-therapy in elderly PDAC patients.
By 2030 70% of newly diagnosed pancreatic ductal adenocarcinoma (PDAC) will occur in older adults. Elderly patients, defined by the World Health Organization (WHO) as people older than 65 years, represent a heterogeneous group with different biological and functional characteristics that need personalized anticancer treatments. Since older patients are under-represented in randomized phase III trials, their management is mostly extrapolated from studies performed in younger patients, without robust evidence-based recommendations. However, data from retrospective studies and case-control series show that elderly may benefit from chemotherapy in both the adjuvant and advanced disease settings. Although with discordant results, gemcitabine-based treatment and dose-adapted fluorouracil combination regimens seem to be effective and well tolerated in this subset of patients.
A proper balance of potential treatment benefits and side effects represent the crucial point for managing elderly patients with PDAC. Therefore an appropriate patient selection is essential to maximize the therapeutic benefit in the older population: randomized studies aiming to better standardizing fitness parameters and implementing the routine use of comprehensive geriatric assessments are strongly warranted. In this light, the detection of molecular prognostic markers able to detect patients who may benefit more from oncological treatments should be a primary endpoint of age-focused clinical trials. Altogether, the field of geriatric oncology will expand in the next years, and the clinical management of elderly patients affected by PDAC will become a major public health issue.
Achyrocline satureioides (Asteraceae) is a medicinal plant traditionally used in Argentina for the treatment of intestinal infections and various digestive disorders. Its infusion is widely utilised ...for respiratory problems and viral infections. The objective of this study was to investigate cytotoxicity, virucidal and antiviral properties of the cold aqueous extract (CAE) and hot aqueous extract (HAE) of this plant against Western equine encephalitis virus (WEEV). Cytotoxicity in Vero cells was evaluated by maximum non-cytotoxic concentration (MNCC), neutral red (NR) uptake and MTT reduction methods. To study the antiviral activity of aqueous extracts, plaque reduction assay was performed after pre-treatment of host cells, adsorption, penetration and post-penetration of the virus. Extracellular virus inactivation was also analysed by the same method. Extracts showed strong inhibitory activity after virus penetration with selective index values of 32 (NR) and 63.3 (MTT) for the CAE, and 16.2 (NR) and 24.3 (MTT) for the HAE. Both extracts exhibited virucidal action with lower efficacy than their antiviral properties. The present results demonstrate that aqueous extracts of A. satureioides are active against WEEV. Further studies are needed in order to identify which compounds could be responsible for this effect, and how they exert antiviral action.
The methanolic extract of Verbascum thapsus was evaluated for its antiviral activity against the pseudorabies virus strain RC/79 (PrV), and also for its cytotoxic activity on Vero cells. The extract ...showed CC
50
values of 1100 µg mL
−1
and 1426 µg mL
−1
by NRU and MTT assays, respectively. The 50% inhibitory concentration of the extract for PrV plaque formation was determined at 35 µg mL
−1
, and selectivity indices were 31.4 (NRU) and 40.7 (MTT). When cells were pre-treated with the extract prior to virus infection, the inhibition in plaque formation was 70%. PrV was highly inhibited when it was incubated with plant extract or when the extract was added during the adsorption phase (99%). However, no inhibitory effect was observed when the extract was added to the cells after the adsorption period. Thus, these results suggest that the methanolic extract of Verbascum thapsus may contain bioactive compound(s) that affect PrV mostly in the adsorption phase.
Abstract Background New chemotherapeutic regimens have improved survival for stage IV pancreatic ductal adenocarcinoma and occasionally major response of liver metastases can be observed. Aim of this ...work is to analyze the outcomes of patients undergoing primary chemotherapy for liver metastases from pancreatic cancer and to evaluate the results of surgical resection. Methods Retrospective analysis. Exclusion criteria: patients with extra-hepatic metastases, patients with Eastern Cooperative Oncology Group performance status ≥ 3, patients undergoing supportive care alone. Results 127 patients were identified. Liver metastases were unilobar in 28.5% of patients. Chemotherapy regimens included gemcitabine alone or in association with other agents (44%), oxaliplatin, irinotecan, fluorouracil and leucovorin (FOLFIRINOX 8%), and cisplatin, gemcitabine plus capecitabine and epirubicin (PEXG) or capecitabine and docetaxel (PDXG) or epirubicin and fluorouracil (PEFG) (48%) . 56 patients (44%) had a complete (7%) or partial response (37%). surgical resection was carried out in 11 patients (8.5%). Median overall survival was 11 months for the entire cohort and 15 months for those with partial/complete response. In this sub-group median survival was significantly longer (46 versus 11 months) for patients undergoing resection (P<0.0001). Independent predictors of overall survival were chemotherapy with multiple agents (HR: 0.512), surgical resection (HR: 0.360), > 5 liver metastases at diagnosis (HR: 3.515), and CA 19.9 reduction < 50% of baseline value (HR: 2.708). Conclusions Surgical resection of primary pancreatic tumor with or without residual liver disease can be considered in selected cases after primary chemotherapy and it is associated with improved survival.
The current trial assessed whether the addition of cisplatin and capecitabine to the nab-paclitaxel–gemcitabine backbone is feasible and active against borderline and locally advanced pancreatic ...adenocarcinoma (PDAC).
Fifty-four chemo-naive patients, aged between 18 and 75 years, with a pathological diagnosis of locally advanced or borderline resectable PDAC were randomised to receive either nab-paclitaxel, gemcitabine, cisplatin and oral capecitabine (PAXG; arm A; N = 26) or nab-paclitaxel followed by gemcitabine (AG; arm B; N = 28).
The primary end-point was the tumour resection rate. If at least four such resections were performed, the treatment was considered as active. The secondary end-points were progression-free survival (PFS), overall survival (OS), Response Evaluation Criteria in Solid Tumours response rate, Hartman's pathologic response, carbohydrate antigen 19.9 response rate and toxicity.
Eight patients (31%) in the PAXG arm and nine (32%) in the AG arm underwent resection. PFS at 1-year was 58% in arm A and 39% in arm B. OS at 18-month was 69% in arm A and 54% in arm B.
In this phase II study, the addition of cisplatin and capecitabine to the AG backbone was feasible and yielded promising results in terms of disease control without detrimental impact on tolerability. The approach warrants further investigation in a phase III study.
NCT01730222.
•No standard therapy has been yet identified in borderline/locally advanced disease.•A very limited number of randomised trials have been completed in this setting.•This current trial evaluates the activity and feasibility of cisplatin, nab-paclitaxel, capecitabine, gemcitabine (PAXG) and nab-paclitaxel, gemcitabine (AG) regimens.•Both regimens were effective in terms of disease control.•PAXG regimen appears more convenient from several perspectives than AG.
Abstract Breast cancer is the leading cause of cancer-related mortality in women worldwide; the most common metastatic sites are lymph nodes, lung, liver, and brain. Tonsil metastases from breast ...cancer are extremely rare. Herein, we report a case of a 74-year-old woman with simultaneous occurrence of tonsillar and cervical lymph nodes metastases after a disease-free interval of 22 years.
Pancreatic ductal adenocarcinoma are known to metastasise early and a rationale exists for the investigation of preoperative chemotherapy in patients with resectable disease. We aimed to assess the ...role of combination chemotherapy in this setting in the PACT-15 trial.
We did this randomised, open-label, phase 2-3 trial in ten hospitals in Italy. We report the phase 2 part here. Patients aged 18-75 years who were previously untreated for pancreatic ductal adenocarcinoma, with Karnofsky performance status of more than 60, and pathologically confirmed stage I-II resectable disease were enrolled. Patients were randomly assigned (1:1:1), with a minimisation algorithm that stratified treatment allocation by centre and concentrations of carbohydrate antigen 19-9 (CA19-9 ≤5 × upper limit of normal ULN vs >5 × ULN), to receive surgery followed by adjuvant gemcitabine 1000 mg/m
on days 1, 8, 15 every 4 weeks for six cycles (arm A), surgery followed by six cycles of adjuvant PEXG (cisplatin 30 mg/m
, epirubicin 30 mg/m
, and gemcitabine 800 mg/m
on days 1 and 15 every 4 weeks and capecitabine 1250 mg/m
on days 1-28; arm B), or three cycles of PEXG before and three cycles after surgery (arm C). Patients and investigators who gave treatments or assessed outcomes were not masked to treatment allocation. The primary endpoint was the proportion of patients who were event-free at 1 year. The primary endpoint was analysed in the per-protocol population. Safety analysis was done for all patients receiving at least one dose of study treatment. The trial is registered with ClinicalTrials.gov, number NCT01150630.
Between Oct 5, 2010, and May 30, 2015, 93 patients were randomly allocated to treatment. One centre was found to be non-compliant with the protocol, and all five patients at this centre were excluded from the study. Thus, 88 patients were included in the final study population: 26 in group A, 30 in group B, and 32 in group C. In the per-protocol population, six (23%, 95% CI 7-39) of 30 patients in group A were event-free at 1 year, as were 15 (50%, 32-68) of 30 in group B and 19 (66%, 49-83) of 29 in group C. The main grade 3 toxicities were neutropenia (five 28% of 18 in group A, eight 38% of 21 in group B, eight 28% of 29 in group C before surgery, and ten 48% of 21 in group C after surgery), anaemia (one 6% in group A, four 19% in group B, eight 28% in group C before surgery, and five 24% in group C after surgery), and fatigue (one 6% in group A, three 14% in group B, two 7% in group C before surgery, and one 5% in group C after surgery). The main grade 4 toxicity reported was neutropenia (two 11% in group A, four 19% in group B, none in group C). Febrile neutropenia was observed in one patient (3%) before surgery in group C. No treatment-related deaths were observed.
Our results provide evidence of the efficacy of neoadjuvant chemotherapy in resectable pancreatic ductal adenocarcinoma. Since the trial began, the standard of care for adjuvant therapy has altered, and other chemotherapy regimens developed. Thus, we decided to not continue with the phase 3 part of the PACT-15. We are planning a phase 3 trial of this approach with different chemotherapy regimens.
PERLAVITA ONLUS and MyEverest ONLUS.