Paclitaxel, vinorelbine and 5-fluorouracil in breast cancer patients pretreated with adjuvant anthracyclines

We investigated the activity and toxicity of a combination of vinorelbine (VNB), paclitaxel (PTX) and 5-fluorouracil (5-FU) continuous infusion administered as first-line chemotherapy in metastatic breast cancer patients pretreated with adjuvant anthracyclines. A total of 61 patients received a regimen consisting of VNB 25 mg m−2 on days 1 and 15, PTX 60 mg m−2 on days 1, 8 and 15 and continuous infusion of 5-FU at 200 mg m−2 every day. Cycles were repeated every 28 days. Disease response was evaluated by both RECIST and World Health Organization (WHO) criteria. Objective responses were recorded in 39 of 61 patients (64.0%) assessed by WHO and in 36 of 50 patients (72.0%) assessable by RECIST criteria. Complete remission occurred in 15 (24.6%) and 14 patients (28.0%), respectively. The median time to progression and overall survival of entire population was 10.6 and 27.3 months, respectively, and median duration of complete response was 14.8 months. The dose-limiting toxicity was myelosuppression (leucopenia grade 3/4 in 52.5% of patients). Grade 3/4 nonhaematologic toxicities included mucositis/diarrhoea in 13.1%, skin in 3.3% and cardiac in 1.6% of patients. Grade 2/3 neurotoxicity was observed in five patients (7.2%). The VNB, PTX and 5-FU continuous infusion combination regimen was active and manageable. Complete responses were frequent and durable

Clinical research in ovarian cancer: consensus recommendations from the Gynecologic Cancer InterGroup

The Gynecologic Cancer InterGroup (GCIG) sixth Ovarian Cancer Conference on Clinical Research was held virtually in October, 2021, following published consensus guidelines. The goal of the consensus meeting was to achieve harmonisation on the design elements of upcoming trials in ovarian cancer, to select important questions for future study, and to identify unmet needs. All 33 GCIG member groups participated in the development, refinement, and adoption of 20 statements within four topic groups on clinical research in ovarian cancer including first line treatment, recurrent disease, disease subgroups, and future trials. Unanimous consensus was obtained for 14 of 20 statements, with greater than 90% concordance in the remaining six statements. The high acceptance rate following active deliberation among the GCIG groups confirmed that a consensus process could be applied in a virtual setting. Together with detailed categorisation of unmet needs, these consensus statements will promote the harmonisation of international clinical research in ovarian cancer

Rickettsia felis, an emerging flea-transmitted human pathogen

Rickettsia felis was first recognised two decades ago and has now been described as endemic to all continents except Antarctica. The rickettsiosis caused by R. felis is known as flea-borne spotted fever or cat-flea typhus. The large number of arthropod species found to harbour R. felis and that may act as potential vectors support the view that it is a pan-global microbe. The main arthropod reservoir and vector is the cat flea, Ctenocephalides felis, yet more than 20 other species of fleas, ticks, and mites species have been reported to harbour R. felis. Few bacterial pathogens of humans have been found associated with such a diverse range of invertebrates. With the projected increase in global temperature over the next century, there is concern that changes to the ecology and distribution of R. felis vectors may adversely impact public health

SPARC: a matricellular regulator of tumorigenesis

Although many clinical studies have found a correlation of SPARC expression with malignant progression and patient survival, the mechanisms for SPARC function in tumorigenesis and metastasis remain elusive. The activity of SPARC is context- and cell-type-dependent, which is highlighted by the fact that SPARC has shown seemingly contradictory effects on tumor progression in both clinical correlative studies and in animal models. The capacity of SPARC to dictate tumorigenic phenotype has been attributed to its effects on the bioavailability and signaling of integrins and growth factors/chemokines. These molecular pathways contribute to many physiological events affecting malignant progression, including extracellular matrix remodeling, angiogenesis, immune modulation and metastasis. Given that SPARC is credited with such varied activities, this review presents a comprehensive account of the divergent effects of SPARC in human cancers and mouse models, as well as a description of the potential mechanisms by which SPARC mediates these effects. We aim to provide insight into how a matricellular protein such as SPARC might generate paradoxical, yet relevant, tumor outcomes in order to unify an apparently incongruent collection of scientific literature

Does co-infection with vector-borne pathogens play a role in clinical canine leishmaniosis?

The severity of canine leishmaniosis (CanL) due to Leishmania infantum might be affected by other vector-borne organisms that mimic its clinical signs and clinicopathological abnormalities. The aim of this study was to determine co-infections with other vector-borne pathogens based on serological and molecular techniques in dogs with clinical leishmaniosis living in Spain and to associate them with clinical signs and clinicopathological abnormalities as well as disease severity. Sixty-one dogs with clinical leishmaniosis and 16 apparently healthy dogs were tested for Rickettsia conorii, Ehrlichia canis, Anaplasma phagocytophilum and Bartonella henselae antigens by the immunofluorescence antibody test (IFAT) and for E. canis, Anaplasma spp., Hepatozoon spp., Babesia spp. and filarioid DNA by polymerase chain reaction (PCR). Among the dogs examined by IFAT, the seroprevalences were: 69% for R. conorii, 57% for E. canis, 44% for A. phagocytophilum and 37% for B. henselae ; while the prevalences found by PCR were: 8% for Ehrlichia / Anaplasma, 3% for Anaplasma platys and 1% for H. canis. No other pathogen DNA was detected. Statistical association was found between dogs with clinical leishmaniosis and seroreactivity to R. conorii antigen (Fisher's exact test: P = 0.025, OR = 4.1, 95% CI = 1-17) and A. phagocytophilum antigen (Fisher's exact test: P = 0.002, OR = 14.3, 95% CI = 2-626) and being positive to more than one serological or molecular tests (co-infections) (Mann-Whitney test: U = 243, Z = -2.6, n = 14, n = 61, P = 0.01) when compared with healthy dogs. Interestingly, a statistical association was found between the presence of R. conorii, E. canis, A. phagocytophilum and B. henselae antibodies in sick dogs and some clinicopathological abnormalities such as albumin and albumin/globulin ratio decrease and increase in serum globulins. Furthermore, seroreactivity with A. phagocytophilum antigens was statistically associated with CanL clinical stages III and IV. This study demonstrates that dogs with clinical leishmaniosis from Catalonia (Spain) have a higher rate of co-infections with other vector-borne pathogens when compared with healthy controls. Furthermore, positivity to some vector-borne pathogens was associated with more marked clinicopathological abnormalities as well as disease severity with CanL

Diagnosis and management of Cornelia de Lange syndrome:first international consensus statement

Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria, both for classic CdLS and non-classic CdLS phenotypes, molecular investigations, long-term management and care planning