Exploring chemotherapy holiday and drugs re-challenge in advanced pancreatic cancer patients.

PURPOSE: We aimed to explore the role of drugs re-challenge at the disease progression after a chemotherapy-free interval for pancreatic adenocarcinoma (PDAC) patients. METHODS: We retrospectively analyzed the outcome of re-treatments at the progression in two cohorts of advanced PDAC patients who had disease control (DC) and a treatment holiday ≥ 3 months after upfront chemotherapy. RESULTS: Between 2015 and 2019, 66 advanced PDAC patients (cohort A) had DC with nab-paclitaxel-based chemotherapy (i.e. AG or PAXG = cisplatin, nab-paclitaxel, gemcitabine, capecitabine). At the time of progressive disease (PD), 34 patients were re-treated with AG (A1) and 32 were treated with other regimens (A2). The median (m) duration of chemotherapy holiday was 6.1 and 5.9 months in A1 and A2, respectively. Partial response (PR) and stable disease (SD) were found in 14 (41%) and 12 (35%) of patients in A1 and in 8 (25%) and 6 (19%) patients in A2. CA19-9 response was recorded in 23/33 evaluable patients (70%) in A1 and in 5/20 (25%) in A2. mPFS2 and mOS2, defined as the time between the second line of treatment start and the disease progression or death, were 4.8 and 12.2 months in A1 and 3.9 and 8.4 months in A2, respectively. Similarly, between 2006 and 2013, 64 patients (cohort B) had DC with upfront PEFG/PEXG/PDXG regimens (epirubicin or docetaxel, cisplatin, gemcitabine, capecitabine or 5-fluorouracil) and were re-treated at PD with either 4-drug (B1; N = 30) or other regimens (B2; N = 34), yielding a mOS2 of 10.9 and 7.2 months, respectively. CONCLUSION: Our data endorse the strategy of resuming prior drugs after a chemotherapy holiday ≥ 3 months in advanced PDAC patients who achieved a  durable disease control after upfront treatments.

Multidrug regimens for treatment of older patients with metastatic pancreatic cancer.

BACKGROUND AND AIMS: Older patients with metastatic pancreatic adenocarcinoma (MPDAC) are under-represented in clinical trials. METHODS: Our single-center, retrospective study enrolled MPDAC patients ≥ 70 treated with chemotherapy RESULTS: 105 patients were divided in groups based on the received treatments: 44 gemcitabine or capecitabine monotherapy (A), 34 nabpaclitaxel-gemcitabine (B) 27 4-drugs combinations (gemcitabine, cisplatin, capecitabine plus either nab-paclitaxel or epirubicin or docetaxel) (C). Group A: median age was 78 (70-87) and Karnofsky performance status (KPS) ≥80 was found in 84% of patients; Group B: median age 77 (71-84) and KPS ≥ 80 in 88% of patients; Group C: median age 73 (70-78) and KPS ≥ 80 in 93% of patients. Median OS was 7.9, 11.7 and 14.2 months in group A, B and C respectively; 1 and 2-year OS were 27% and 8% in group A; 44% and 5% in group B; 52% and 22% in group C. When lung metastatic only patients were excluded, patients <75 and ≥ 75 had similar OS in group A (6.4 vs 5.6 months) and in group B (12.3 vs 11.1 months). In group B grade 3 thrombocytopenia, fatigue and peripheral neuropathy were more frequent in patients ≥ 75. CONCLUSIONS: In older patients, combination chemotherapy shows acceptable feasibility and promising efficacy.

Time to CA19-9 nadir: a clue for defining optimal treatment duration in patients with resectable pancreatic ductal adenocarcinoma.

BACKGROUND: Defining optimal treatment duration in patients with resectable pancreatic ductal adenocarcinoma (PDAC) receiving primary chemotherapy is an unmet need. The role of time to CA19-9 nadir and of nadir magnitude was explored in this study. PATIENTS AND METHODS: The databases of our institution's prospective trials were queried to speculate on the time to maximum chemotherapy response. Patients with pathologically proven, metastatic (N = 356) or non-metastatic non-resected (N = 163) PDAC and elevated baseline (> 34 UI/mL) CA19-9 were analyzed. Survival curves were estimated using the Kaplan-Meier method and compared by means of the log-rank test for analyses including at least 45 patients. Multivariable Cox proportional hazards model was used to estimate clinical features for their association with OS. All probability values were from two-sided tests. RESULTS: Time to CA19-9 nadir was ≥ 4 months in 184 of 346 (53%) metastatic and 121 of 163 (74%) non-metastatic patients (p = 0.002). The likelihood of a later nadir was higher with taxane-based chemotherapy as compared to taxane-free combinations (73% versus 56%; p = 0.02). Both metastatic and non-metastatic patients had significantly longer survival when nadir occurred later. Patients with a larger CA19-9 nadir magnitude had significantly longer survival. Metastatic patients with CA19-9 reduced by < 50%, 50-89%, or > 89% and had a median survival of 7.4, 9.8, and 14.7 months, respectively (p ≤ 0.001 for all comparisons). The corresponding figures for non-metastatic patients were 10.6; 17.0; and 18.7 months, respectively (p ≤ 0.02 for < 50% versus 50-89% or > 89%; p = 0.14 for 50-89% versus > 89%). Multivariable analyses showed that time to CA19-9 nadir but not CA19-9 nadir magnitude was independently predictive of survival. CONCLUSION: The present study suggests that a 4-6 months program might be a more suitable candidate for prospective assessment in comparison to shorter pre-defined period in patients who are candidates to surgery after primary chemotherapy.

Early variation of 18-fluorine-labelled fluorodeoxyglucose PET-derived parameters after chemoradiotherapy as predictors of survival in locally advanced pancreatic carcinoma patients.

OBJECTIVE: To investigate if early variation of PET-derived parameters after concomitant chemoradiotherapy (CRT) predicts overall survival (OS), local relapse free survival (LRFS), distant relapse free survival (DRFS) and progression free survival (PFS) in locally advanced pancreatic cancer (LAPC) patients. METHODS: Fifty-two LAPC patients (median age: 61 years; range: 35-85) with available FDG PET/CT before and after RT (2-6 months, median: 2) were enrolled from May 2005 to June 2015. The predictive value of the percentage variation of mean/maximum standard uptake value (ΔSUVmean/max), metabolic tumour volume (ΔMTV) and total lesion glycolysis (ΔTLG), estimated considering different uptake thresholds (40-50-60%), was investigated between pre- and post-RT PET. The percentage difference between gastrointestinal cancer-associated antigen (ΔGICA) levels measured at the time of PET was also considered. Log-rank test and Cox regression analysis were performed to assess the prognostic value of considered PET-derived parameters on survival outcomes. RESULTS: The median follow-up was 13 months (range: 4-130). At univariate analysis, ΔTLG50 showed borderline significance in predicting OS (P = 0.05) and was the most significant parameter correlated to LRFS and PFS (P = 0.001). Median LRFS was 4 and 33 months if ΔTLG50 was below or above 35% respectively (P = 0.0003); similarly, median PFS was 3 vs 6 months (P = 0.0009). No significant correlation was found between PET-derived parameters and DRFS, while the ΔGICA was the only borderline significant prognostic value for this endpoint (P = 0.05). CONCLUSION: PET-derived parameters predict survival in LAPC patients; in particular, ΔTLG50 is the strongest predictor. The combination of these biochemical and imaging biomarkers is promising in identifying patients at higher risk of earlier relapse.

Chemotherapy in elderly patients with pancreatic cancer: Efficacy, feasibility and future perspectives.

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.

Biomarker-driven and molecularly targeted therapies for pancreatic adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) remains a deadly disease with few effective treatment options. Our knowledge of molecular alterations in PDAC has significantly grown and helped identify new therapeutic targets. The success of immune checkpoint inhibition in mismatch repair deficient tumors, PARP inhibitors for tumors with DNA repair defects, and targeting hyaluronan with PEGPH20 in patients with high expressing (hyaluronan-high) tumors are examples of promising biomarker-driven therapies. We review the major biological mechanisms in PDAC and discuss current and future directions for molecularly targeted therapies in this disease.

Nab-paclitaxel plus gemcitabine with or without capecitabine and cisplatin in metastatic pancreatic adenocarcinoma (PACT-19): a randomised phase 2 trial.

BACKGROUND: Current treatment for metastatic pancreatic ductal adenocarcinoma includes combination chemotherapy, such as FOLFIRINOX or nab-paclitaxel plus gemcitabine. We investigated the activity of a novel four-drug regimen, consisting of cisplatin, nab-paclitaxel, capecitabine, and gemcitabine, compared with nab-paclitaxel plus gemcitabine, in the PACT-19 trial. METHODS: This single-centre, randomised, open-label, phase 2 trial was done in San Raffaele Hospital in Italy. We enrolled patients aged 18-75 years with pathologically confirmed stage IV pancreatic ductal adenocarcinoma who had received no previous chemotherapy and had Karnofsky performance status of at least 70. Patients were randomly assigned (1:1) by computer-generated permutated block randomisation (block size of four) stratified by baseline concentration of carbohydrate antigen 19-9 to PAXG (cisplatin 30 mg/m2, nab-paclitaxel 150 mg/m2, and gemcitabine 800 mg/m2 on days 1 and 15 and oral capecitabine 1250 mg/m2 on days 1-28 every 4 weeks), or nab-paclitaxel and gemcitabine alone (nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 on days 1, 8, and 15 every 4 weeks). The primary endpoint was the proportion of patients who were progression-free at 6 months, analysed in the intention-to-treat population. Data cutoff was on March 31, 2018. The safety population included all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01730222, and is now closed. FINDINGS: Between April 22, 2014, and May 30, 2016, we randomly assigned 83 patients to treatment: 42 patients to PAXG and 41 patients to nab-paclitaxel plus gemcitabine. At 6 months, 31 (74%, 95% CI 58-86) of 42 patients in the PAXG group were alive and free from disease progression compared with 19 (46%, 31-63) of 41 patients in the nab-paclitaxel plus gemcitabine group. The most frequent grade 3 adverse events were neutropenia (12 [29%] of 42 in the PAXG group vs 14 [34%] of 41 in the nab-paclitaxel plus gemcitabine group), anaemia (nine [21%] vs nine [22%]), and fatigue (seven [17%] vs seven [17%]). The most common grade 4 adverse event was neutropenia (five [12%] in the PAXG group vs two [5%] in the nab-paclitaxel plus gemcitabine group). Two (5%) treatment-related deaths occurred in the nab-paclitaxel plus gemcitabine group compared with none in the PAXG group. INTERPRETATION: Despite the small sample size, our findings suggest that the PAXG regimen warrants further investigation in a phase 3 trial in patients with metastatic pancreatic ductal adenocarcinoma. FUNDING: Celgene.

A randomised phase 2 trial of nab-paclitaxel plus gemcitabine with or without capecitabine and cisplatin in locally advanced or borderline resectable pancreatic adenocarcinoma.

BACKGROUND: 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). METHOD: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: NCT01730222.

Safety and efficacy of preoperative or postoperative chemotherapy for resectable pancreatic adenocarcinoma (PACT-15): a randomised, open-label, phase 2-3 trial.

BACKGROUND: 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. METHODS: 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/m2 on days 1, 8, 15 every 4 weeks for six cycles (arm A), surgery followed by six cycles of adjuvant PEXG (cisplatin 30 mg/m2, epirubicin 30 mg/m2, and gemcitabine 800 mg/m2 on days 1 and 15 every 4 weeks and capecitabine 1250 mg/m2 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: PERLAVITA ONLUS and MyEverest ONLUS.

Central nervous system gliomas.

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.

Osteopathic Manipulative Treatment Limits Chronic Constipation in a Child with Pitt-Hopkins Syndrome.

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.

Phase 1B trial of Nab-paclitaxel plus gemcitabine, capecitabine, and cisplatin (PAXG regimen) in patients with unresectable or borderline resectable pancreatic adenocarcinoma.

BACKGROUND: Nab-paclitaxel-gemcitabine combination significantly improved overall survival over gemcitabine in metastatic pancreatic adenocarcinoma. A phase 1b trial was performed (ClinicalTrials.gov number, NCT01730222) to determine the recommended phase 2 dose (RP2D) of nab-paclitaxel in combination with cisplatin, capecitabine, and gemcitabine at fixed dose (800, 30, and 1250 mg m(-2) every 2 weeks, respectively; PAXG regimen). METHODS: Nab-paclitaxel doses were escalated from 100 (level one) to 125 (level two) and 150 mg m(-2) (level three) every 2 weeks in cohorts of 3-6 patients with pathologically confirmed unresectable or borderline resectable pancreatic adenocarcinoma. RESULTS: Between Dec 2012 and Apr 2014, 24 patients were enroled (3 at level one, 5 at level two, 16 at level three) and received 117 cycles of PAXG. No dose-limiting toxicity occurred and level three was the RP2D. At this dose, nab-paclitaxel dose-intensity was 91%. Worse per patient grade 3/4 toxicity were neutropenia 25/31%; fatigue 19%; anaemia and hand-foot syndrome 12%, nausea 6%, and febrile neutropenia 6%. A partial response (PR) was observed in 16 (67%) and stable disease (SD) in 8 patients (33%). Among 21 patients with a baseline positive positron emission tomography (PET) scan, a complete metabolic response was observed in 9 (43%), PR in 10 (48%), SD in 2. CA19-9 decreased by ⩾49% in all the 19 patients with elevated basal value. Six patients were resected after chemotherapy. Progression-free survival at 6 months (PFS-6) was 96%. CONCLUSIONS: The RP2D of nab-paclitaxel in the PAXG regimen was 150 mg m(-2) every 2 weeks. The preliminary results are promising and warrant further exploration.

Hydroxyurea with or without imatinib in the treatment of recurrent or progressive meningiomas: a randomized phase II trial by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO).

PURPOSE: Hydroxyurea (HU) is among the most widely used salvage therapies in progressive meningiomas. Platelet-derived growth factor receptors are expressed in virtually all meningiomas. Imatinib sensitizes transformed cells to the cytotoxic effects of chemotherapeutic agents that interfere with DNA metabolism. The combination of HU with imatinib yielded intriguing results in recurrent malignant glioma. The current trial addressed the activity of this association against meningioma. METHODS: Patients with recurrent or progressive WHO grade I-III meningioma, without therapeutic indication for surgery, radiotherapy, or stereotactic radiosurgery, aged 18-75 years, ECOG performance status 0-2, and not on enzyme-inducing anti-epileptic drugs were randomized to receive HU 500 mg BID ± imatinib 400 mg QD until progression, unacceptable toxicity, or patient's refusal. The primary endpoint was progression-free survival rate at 9 months (PFS-9). RESULTS: Between September 2009 and February 2012, 15 patients were randomized to receive HU + imatinib (N = 7; Arm A) or HU alone (N = 8; Arm B). Afterward the trial was prematurely closed due to slow enrollment rate. PFS-9 (A/B) was 0/75%, and median PFS was 4/19.5 months. Median and 2-year overall survival (A/B) rates were: 6/27.5 months; 28.5/75%, respectively. Main G3-4 toxicities were: G3 neutropenia in 1/0, G4 headache in 1/1, and G3 vomiting in 1/0. CONCLUSION: The conduction of a study in recurrent or progressive meningioma remains a challenge. Given the limited number of patients enrolled, no firm conclusions can be drawn about the combination of imatinib and HU. The optimal systemic therapy for meningioma failing surgery and radiation has yet to be identified.

Lack of cytotoxic and genotoxic effects of Minthostachys verticillata essential oil: studies in vitro and in vivo.

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 (100-1000 µg/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 (25-500 mg/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.

Late onset (22 years) of simultaneous tonsillar and cervical lymph node metastases from breast ductal carcinoma.

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.

Antiviral effect and mode of action of methanolic extract of Verbascum thapsus L. on pseudorabies virus (strain RC/79).

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 CC50 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.

Evaluation of antiviral activity of aqueous extracts from Achyrocline satureioides against Western equine encephalitis virus.

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.

Genotoxic evaluation of a methanolic extract of Verbascum thapsus using micronucleus test in mouse bone marrow.

Verbascum thapsus L. is a medicinal plant and has been used to treat numerous pulmonary diseases, asthma, inflammatory disease, spasmodic coughs and migraine headaches. Several studies have demonstrated that different extracts of V. thapsus present antimicrobial activity. Thus, the goal of this study was to evaluate the genotoxic and cytotoxic activities of a methanolic extract of Verbascum thapsus, using micronucleus test in mouse bone marrow. No toxicity in bone marrow was detected in the extract-treated groups. The methanolic extract of V. thapsus at doses of 100, 300 and 500 mg/kg, did not produce a significant increase in the frequency of MNPCE in bone marrow and neither altered the relationship PCE/NCE respect to negative control. These cytogenotoxic findings contribute the preclinical knowledge of methanolic extract of V. thapsus and provide security in its use as herbal medicine.

Study of antiviral and virucidal activities of aqueous extract of Baccharis articulata against Herpes suis virus.

Baccharis articulata is native of América and traditionally used for the treatment of digestive disorders and urinary infections. Cytotoxicity of aqueous extracts of B. articulata was investigated in Vero cells. As the maximal non cytotoxic concentration has been established, this concentration has been used to evaluate antiviral and virucidal activities against Herpes suis virus type 1, member of the same subfamily of Herpes simplex virus. Aqueous extracts of B. articulata exhibited more than 95% of virucidal activity. These findings support their potential application as a disinfectant or antiseptic with low toxicity and provide a valuable knowledge to ethnopharmacology properties of Baccharis articulata.