RESUMO
In oncologic patients fever is a non-specific clinical marker of different clinical settings. Procalcitonin (PCT) seems to be the most promising infection marker. We aimed to define the potential role of PCT as an earlier diagnostic marker in patients with fever and solid tumor. This retrospective study enrolled 431 patients. All of them performed hemoculture (HE) and basal PCT assessment (reference laboratory cut-off: ≤0.5 or >0.5 ng/dL) before starting antibiotic therapy. Gram positive (G+), negative (G-) or Fungi infection were detected. A statistically significant difference in PCT levels between patients with positive and negative HE was observed (P < 0.0001). Moreover comparing PCT values in patients with positive and negative HE, we obtain in the positive HE subpopulation an AUC of 0.7 and a cut-off of 1.52 ng/dL reached high sensitivity (61.6%) and specificity (70.1%). Using this last cut-off, instead of the normal reference value, we achieve a risk reduction to overestimate an infection status of 23.4%. We support the clinic usefulness of serum PCT dosage in febrile advanced solid tumor patients. A PCT cut-off of 1.52 ng/dL could be helpful in the management of the antibiotic therapy preventing delays of oncologic treatments.
Assuntos
Calcitonina/sangue , Febre/etiologia , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Positivas/diagnóstico , Micoses/diagnóstico , Neoplasias/complicações , Adolescente , Adulto , Idoso , Área Sob a Curva , Biomarcadores/sangue , Hemocultura , Feminino , Infecções por Bactérias Gram-Negativas/complicações , Infecções por Bactérias Gram-Positivas/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Micoses/complicações , Neoplasias/patologia , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto JovemRESUMO
Human adenoviruses (HAdVs) cause a wide spectrum of clinical syndromes, depending on species and types, from mild respiratory infections to deadly pneumonia: in particular, severe infections occur in immunocompromised patients. In this report, we describe the case of a 36 years-old woman admitted to our intensive care unit (ICU) with severe respiratory distress syndrome caused by adenovirus pneumonia, that required invasive respiratory support (mechanical ventilation and extracorporeal membrane oxygenation). Molecular assays detected the virus in respiratory and plasma specimen and sequencing procedure identified HAdV type 4. Patient improved after cidofovir administration. Leukopenia and subsequent bacterial infection occurred, but the patient recovered completely and was discharged from the hospital after 54days.
Assuntos
Infecções por Adenovirus Humanos , Adenovírus Humanos/genética , Síndrome do Desconforto Respiratório , Adulto , Cuidados Críticos , DNA Viral/análise , DNA Viral/genética , Feminino , Hospitalização , Humanos , Tipagem Molecular , Reação em Cadeia da PolimeraseRESUMO
Renal cell carcinoma is an aggressive disease often asymptomatic and weakly chemo-radiosensitive. Currently, new biologic drugs are used among which everolimus, an mTOR inhibitor, that has been approved for second-line therapy. Since mTOR is involved in the control of autophagy, its antitumor capacity is often limited. In this view, chloroquine, a 4-alkylamino substituted quinoline family member, is an autophagy inhibitor that blocks the fusion of autophagosomes and lysosomes. In the present study, we evaluated the effects of everolimus alone or in combination with chloroquine on renal cancer cell viability and verified possible synergism. Our results demonstrate that renal cancer cells are differently sensitive to everolimus and chloroquine and the pharmacological combination everolimus/chloroquine was strongly synergistic inducing cell viability inhibition. In details, the pharmacological synergism occurs when chloroquine is administered before everolimus. In addition, we found a flow autophagic block and shift of death mechanisms to apoptosis. This event was associated with decrease of Beclin-1/Bcl(-)2 complex and parallel reduction of anti-apoptotic protein Bcl(-)2 in combined treatment. At last, we found that the enhancement of apoptosis induced by drug combination occurs through the intrinsic mitochondrial apoptotic pathway activation, while the extrinsic pathway is involved only partly following its activation by chloroquine. These results provide the basis for new therapeutic strategies for the treatment of renal cell carcinoma after appropriate clinical trial.
Assuntos
Antineoplásicos/farmacologia , Autofagia/efeitos dos fármacos , Carcinoma de Células Renais/tratamento farmacológico , Cloroquina/farmacologia , Everolimo/farmacologia , Neoplasias Renais/tratamento farmacológico , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Proteína Beclina-1 , Carcinoma de Células Renais/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Neoplasias Renais/genética , Lisossomos/efeitos dos fármacos , Proteínas de Membrana/genética , Mitocôndrias/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/genéticaRESUMO
BACKGROUND: KRAS wild-type mutational status is necessary but not sufficient to get benefit from epidermal growth factor receptor inhibition. Predictive markers are currently being evaluated. In this study, we investigated early hypomagnesemia as a predictor of efficacy and outcome in terms of time to progression (TtP) and overall survival (OS) in a cohort of patients affected by advanced colorectal adenocarcinoma KRAS wild-type cetuximab-treated. PATIENTS AND METHODS: One hundred and forty-three patients affected by stage IV colorectal adenocarcinoma KRAS wild type receiving cetuximab + irinotecan (CTX+IRI) as third-line anticancer treatment and resistant to oxaliplatin- and irinotecan-based chemotherapy were retrospectively included. Magnesium plasma levels were measured before the first day and 7, 14, 21 and 28 days after CTX+IRI infusion. RESULTS: The median magnesium basal value showed a statistically significant decrease after the start of CTX+IRI treatment (at 28 days, P < 0.0001). Patients with an early decrease of magnesium levels >50% compared with the basal level had a higher tumor response rate (55.8% versus 16.7%, P < 0.0001), a longer TtP (6.3 versus 3.6, P < 0.0001) and a longer median OS (11.0 versus 8.1, P = 0.002). CONCLUSIONS: We have shown that early hypomagnesemia could be a predictor of efficacy and outcome in those patients. Magnesium circulating level is an easy and inexpensive biomarker to routinely be detected in patients treated with cetuximab.
Assuntos
Adenocarcinoma/sangue , Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Neoplasias Colorretais/tratamento farmacológico , Magnésio/sangue , Proteínas Proto-Oncogênicas/genética , Proteínas ras/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Cetuximab , Neoplasias Colorretais/sangue , Intervalo Livre de Doença , Feminino , Genótipo , Humanos , Irinotecano , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Proteínas Proto-Oncogênicas p21(ras) , Estudos RetrospectivosRESUMO
Bone metastases have a major impact on morbidity and on mortality in cancer patients. Despite its clinical relevance, metastasis remains the most poorly elucidated aspect of carcinogenesis. The biological mechanisms leading to bone metastasis establishment have been referred as "vicious circle," a complex network between cancer cells and the bone microenvironment. This review is aimed to underline the new molecular targets in bone metastases management other than bisphosphonates. Different pathways or molecules such as RANK/RANKL/OPG, cathepsin K, endothelin-1, Wnt/DKK1, Src have recently emerged as potential targets and nowadays preclinical and clinical trials are underway. The results from those in the advanced clinical phases are encouraging and underlined the need to design large randomised clinical trials to validate these results in the next future. Targeting the bone by preventing skeletal related events (SREs) and bone metastases has major clinical impact in improving survival in bone metastatic patients and in preventing disease relapse in adjuvant setting.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Animais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Neoplasias Ósseas/metabolismo , Catepsina K/efeitos dos fármacos , Catepsina K/metabolismo , Denosumab , Endotelinas/efeitos dos fármacos , Endotelinas/metabolismo , Humanos , Proteínas Proto-Oncogênicas pp60(c-src)/efeitos dos fármacos , Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo , Ligante RANK/efeitos dos fármacos , Ligante RANK/metabolismo , Ligante RANK/uso terapêuticoAssuntos
Adenocarcinoma/terapia , Anticorpos Monoclonais/uso terapêutico , Neoplasias Intestinais/terapia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Cetuximab , Terapia Combinada , Feminino , Humanos , Imunoterapia , Neoplasias Intestinais/mortalidade , Neoplasias Intestinais/patologia , Intestino Delgado/patologia , Irinotecano , Masculino , Pessoa de Meia-Idade , SobrevidaAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Deficiência de Vitamina D/etiologia , Vitamina D/sangue , Antraciclinas/uso terapêutico , Quimioterapia Adjuvante , Docetaxel , Feminino , Humanos , Estudos Longitudinais , Taxoides/uso terapêutico , Deficiência de Vitamina D/complicaçõesRESUMO
We report the stopping power of molecular hydrogen for antiprotons of kinetic energy above the maximum (approximately 100 keV) with the purpose of comparing with the proton one. Our result is consistent with a positive difference in antiproton-proton stopping powers above approximately 250 keV and with a maximum difference between the stopping powers of 21%+/-3% at around 600 keV.
RESUMO
The unknown etiopathogenesis of psoriasis and its often unpredictable course, in spite of actual treatment, suggest the search of parameters correlated with the disease that could help to better define and treat these patients. The altered cell turnover of the psoriatic epidermis leads to hypothesize a disturbance or at least a modification of the cellular rhythm of the skin. In order to prove alterations of the circadian temporal structure in psoriasis, we have studied some easily detectable variables, registered at 3-h intervals, in both psoriatic and in healthy control subjects. The control subjects presented statistically significant circadian rhythms of oral temperature, arterial blood pressure, pulse, electrolytes, 17KS, 17-OHCS and uricemia. In the psoriatic group, only a few of these variables present a clearly reproducible circadian rhythm. Moreover these rhythms, when they are demonstrable in the patients, do not show the same circadian acrophases of the control subjects and they are also desynchronized inside the group itself. The alteration in these circadian urinary and haematic rhythms implies that in psoriasis not only the skin is involved: all the circadian structure seems to be perturbed and the cause of the disease should mot be searched only in the epidermis.