Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 92
Filtrar
1.
Ann Glob Health ; 87(1): 81, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34434717

RESUMO

One of the major problems facing healthcare systems in countries with poor socio-economic conditions is the need to strengthen the system through the training of physicians, nurses and other healthcare operators. Partnering with more affluent countries is the key for hospitals in these areas, but such alliances are often based on limited educational exchanges. We present a retrospective study of our experience in building a collaborative relationship between our cancer institute in Italy and a Medical Center in sub-Saharan Africa (Tanzania). The main purpose is to see the changes in the clinical practice after educational interventions on health personnel in a Tanzanian cancer center.


Assuntos
Atenção à Saúde , Cooperação Internacional , Oncologia , Comportamento Cooperativo , Currículo , Pessoal de Saúde , Humanos , Itália , Oncologia/educação , Avaliação de Programas e Projetos de Saúde , Estudos Retrospectivos , Tanzânia
2.
Int J Mol Sci ; 22(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207126

RESUMO

Although immune checkpoint inhibitors have changed the treatment paradigm of a variety of cancers, including non-small-cell lung cancer, not all patients respond to immunotherapy in the same way. Predictive biomarkers for patient selection are thus needed. Tumor mutation burden (TMB), defined as the total number of somatic/acquired mutations per coding area of a tumor genome (Mut/Mb), has emerged as a potential predictive biomarker of response to immune checkpoint inhibitors. We found that the limited use of TMB in clinical practice is due to the difficulty in its detection and compounded by several different biological, methodological and economic issues. The incorporation of both TMB and PD-L1 expression or other biomarkers into multivariable predictive models could result in greater predictive power.


Assuntos
Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/genética , Predisposição Genética para Doença , Neoplasias Pulmonares/genética , Mutação , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Ensaios Clínicos como Assunto , Gerenciamento Clínico , Estudos de Associação Genética , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Terapia de Alvo Molecular , Avaliação de Resultados da Assistência ao Paciente
3.
Sci Rep ; 11(1): 9777, 2021 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-33963223

RESUMO

Bladder cancer (BCa) patients are diagnosed by cytology and cystoscopy. However, these diagnostic tests bear some limitations. We sought for reliable biomarkers to better determine BCa extension. Prostate-specific membrane antigen (PSMA) appears to fulfill this requirement in prostate cancer but its role in BCa has not been established yet. We then analyzed 87 bladder tissue samples from 74 patients assessing PSMA expression by immunohistochemistry. The median PSMA expression, exclusively found in tumor neovasculature, in terms of H-score significantly differed between non-tumor samples and tumor samples (p = 0.00288) showing a higher neovasculature-related PSMA expression. No differences were observed in relation to tumor type, grade and stage. BCa neovasculature-related PSMA overexpression may be useful in defining the degree of extension of the neoplasm. In addition, testing PSMA expression by immunohistochemistry may hold theranostic implications both considering anti-angiogenesis agents and radio-labelled PSMA ligands for intracavitary radionuclide therapy. In our opinion, BCa neovasculature-related PSMA overexpression may be considered an apt target for anti-angiogenesis and radionuclide treatment in BCa, once the evaluation of tumor-retention time for the appropriateness of long half-life therapeutic PSMA ligands as radionuclide treatment will be performed.


Assuntos
Antígenos de Superfície/biossíntese , Biomarcadores Tumorais/biossíntese , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Glutamato Carboxipeptidase II/biossíntese , Proteínas de Neoplasias/biossíntese , Neoplasias da Bexiga Urinária , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia
4.
Transl Lung Cancer Res ; 10(4): 1819-1828, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34012795

RESUMO

Background: Programmed death protein (ligand) 1 [PD-(L)1] inhibitors have provided new therapeutic options for advanced lung cancer. However, patients with hepatitis B virus (HBV) infection have been traditionally excluded from most registered trials of this form of treatment. Methods: We performed a retrospective analysis of patients with HBV and advanced lung cancer who received anti-PD-1 immunotherapy from September 2018 to May 2020 in our department. Treatment-related hepatotoxicity was evaluated and recorded. Overall response rate and progression free survival were also assessed in the patients using iRECIST. Results: Seventeen patients were evaluated in this analysis. Of these, six (35.3%) experienced hepatic transaminase elevation during immunotherapy. Three of these patients developed Grade 3 hepatic immune-related adverse events and received systemic corticosteroids, following which aminotransferase levels recovered to normal in all patients and no adverse events were observed in subsequent treatment. No patient experienced HBV reactivation or flare. One patient developed active pulmonary tuberculosis (TB). Other adverse events were mild, well tolerated and short term. The objective response rate (ORR) of the cohort was 62.5%, and the median progression-free survival (PFS) was 3 months. Conclusions: Lung cancer patients can be treated safely with anti-PD-1 inhibitors in the context of HBV infection. Close monitoring for hepatotoxicity and prophylactic antiviral therapy is advised. Further studies on the use of anti-PD-1 inhibitors in HBV-infected patients are needed.

5.
Front Oncol ; 11: 669839, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34017688

RESUMO

Background: Current therapy for non-small-cell lung cancer (NSCLC) frequently includes immune checkpoint inhibitors, such as pembrolizumab, and programmed death ligand 1 (PD-L1) positivity is mandatory for its use in this setting. Vimentin plays a role in carcinogenesis through the activation of the epithelial-to-mesenchymal transition (EMT) process. Its prognostic impact in NSCLC has been investigated in numerous studies but little data are available on its relation with PD-L1 expression. Patients and Methods: We retrospectively retrieved data on patients with advanced NSCLC consecutively enrolled in a clinical trial at our institute. PD-L1 and vimentin expression were determined by immunohistochemistry. Correlations between variables were assessed using the Spearman correlation coefficient. The Kaplan-Meier method was used to estimate overall survival (OS) and the Log-rank test was used to compare survival curves. The association between demographic, clinical and biomarker information and survival was investigated with the Cox model. Results: Fifty-three patients were included in the study. A weak positive correlation was observed between the PD-L1 and vimentin (ρ=0.41, P=0.003). Patients with PD-L1 values <1% showed a slightly better OS than those with higher values (HR=2.07; 95% CI: 0.92-4.65), but the difference was not significant (P=0.080). No difference in overall survival (OS) was observed on the basis of vimentin expression (HR=1.25; 95% CI: 0.59-2.66; P=0.554). Patients harboring both vimentin and PD-L1 negative expression (<1%) showed a trend towards better survival than those with ≥1% expression (HR=2.31; 95% CI: 0.87-6.17, P=0.093). No significant associations were observed between gender, age at diagnosis, stage at diagnosis, histology, KRAS or EGFR status, radical surgery or immunotherapy and OS. Conclusions: The weak positive association between PD-L1 and vimentin suggests a potential interplay between these biomarkers. Further research is warranted to evaluate EMT and immune escape as two components of the same process.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33808259

RESUMO

In recent years, lipid metabolism has gained greater attention in several diseases including cancer. Dysregulation of fatty acid metabolism is a key component in breast cancer malignant transformation. In particular, de novo lipogenesis provides the substrate required by the proliferating tumor cells to maintain their membrane composition and energetic functions during enhanced growth. However, it appears that not all breast cancer subtypes depend on de novo lipogenesis for fatty acid replenishment. Indeed, while breast cancer luminal subtypes rely on de novo lipogenesis, the basal-like receptor-negative subtype overexpresses genes involved in the utilization of exogenous-derived fatty acids, in the synthesis of triacylglycerols and lipid droplets, and fatty acid oxidation. These metabolic differences are specifically associated with genomic and proteomic changes that can perturb lipogenic enzymes and related pathways. This behavior is further supported by the observation that breast cancer patients can be stratified according to their molecular profiles. Moreover, the discovery that extracellular vesicles act as a vehicle of metabolic enzymes and oncometabolites may provide the opportunity to noninvasively define tumor metabolic signature. Here, we focus on de novo lipogenesis and the specific differences exhibited by breast cancer subtypes and examine the functional contribution of lipogenic enzymes and associated transcription factors in the regulation of tumorigenic processes.


Assuntos
Neoplasias da Mama , Lipogênese , Ácidos Graxos , Humanos , Metabolismo dos Lipídeos , Proteômica
7.
Methods Mol Biol ; 2292: 3-15, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33651347

RESUMO

Recent reports suggest that urine is a useful noninvasive tool for the identification of urogenital tumors, including bladder, prostate, kidney, and other nonurological cancers. As a liquid biopsy, urine represents an important source for the improvement of new promising biomarkers, a suitable tool to identify indolent cancer and avoid overtreatment. Urine is enriched with DNAs, RNAs, proteins, circulating tumor cells, exosomes, and other small molecules which can be detected with several diagnostic methodologies.We provide an overview of the ongoing state of urinary biomarkers underlying both their potential utilities to improve cancer prognosis, diagnosis, and therapeutic strategy and their limitations.


Assuntos
Biomarcadores Tumorais/urina , Neoplasias/urina , Animais , Ácidos Nucleicos Livres/urina , Exossomos/patologia , Humanos , Biópsia Líquida/métodos , Neoplasias/diagnóstico , Neoplasias/patologia , Ácidos Nucleicos/urina , Proteínas , Proteinúria/diagnóstico , Proteinúria/patologia , Proteinúria/urina , Urinálise/métodos
8.
Methods Mol Biol ; 2292: 35-48, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33651350

RESUMO

Cystoscopy is considered the standard approach to the diagnostic workup of urinary symptoms. It has high sensitivity and specificity for papillary tumors of the bladder but low sensitivity and specificity for flat lesions. It is also expensive and may cause discomfort and complications. Urine cytology, in contrast, has the advantage of being a noninvasive test with high specificity but suffers from low sensitivity in low-grade and early-stage tumors, possibly due to the low number of exfoliated cells in urine. Numerous new noninvasive tests have been proposed. Among these, fluorescence in situ hybridization (FISH) has been studied for long time and in 2005 UroVysion Bladder Cancer Kit (UroVysion Kit) (Abbott/Vysis) received FDA approval for initial diagnosis of bladder carcinoma in patients with hematuria and subsequent monitoring for tumor recurrence in patients previously diagnosed with bladder cancer. The UroVysion Kit is designed to detect aneuploidy for chromosomes 3, 7, 17, and loss of the 9p21 locus by FISH in urine specimens from symptomatic patients, those with hematuria suspected of having bladder cancer. Here, the approach for FISH assay by using UroVysion Bladder Cancer kit according to manufacturer's instructions is described.


Assuntos
Hematúria/urina , Hibridização in Situ Fluorescente/métodos , Neoplasias da Bexiga Urinária/urina , Aneuploidia , Cromossomos Humanos/genética , Hematúria/genética , Humanos , Neoplasias da Bexiga Urinária/genética
9.
Methods Mol Biol ; 2292: 133-141, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33651358

RESUMO

Bladder cancer with an incidence of 15 cases per 100,000 persons in the global population is the most common tumor of the urinary tract. Imaging techniques, cytoscopy, and cytology are not sufficiently accurate to detect early stage tumors, and the need for new diagnostic markers is still an urgency. Among the biomarkers most recently proposed to improve diagnostic accuracy and especially sensitivity, increasing attention has been focused on the role of the ribonucleoprotein, telomerase. Previous studies have shown that the quantitative telomerase repeat amplification protocol (TRAP) assay performed in voided urine is an important noninvasive tool for the diagnosis of bladder tumors since it has very high sensitivity and specificity, even for early stage and low-grade tumors. Telomerase activity in urine determined by TRAP seems to be marker of great potential, even more advantageous in cost-benefit terms when used in selected symptomatic patients or professionally high-risk subgroups. Here we report the real-time PCR protocol to detect telomerase activity in urine sediment for bladder cancer.


Assuntos
Telomerase/urina , Neoplasias da Bexiga Urinária/urina , Biomarcadores Tumorais/urina , Ensaios Enzimáticos/métodos , Humanos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Coleta de Urina/métodos
10.
Sci Rep ; 11(1): 2980, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536459

RESUMO

While the molecular functions of miR-200 family have been deeply investigated, a role for these miRNAs as breast cancer biomarkers remains largely unexplored. In the attempt to clarify this, we profiled the miR-200 family members expression in a large cohort of breast cancer cases with a long follow-up (H-CSS cohort) and in TCGA-BRCA cohort. Overall, miR-200 family was found upregulated in breast tumors with respect to normal breast tissues while downregulated in more aggressive breast cancer molecular subtypes (i.e. Luminal B, HER2 and triple negative), consistently with their function as repressors of the epithelial-to-mesenchymal transition (EMT). In particular miR-141-3p was found differentially expressed in breast cancer molecular subtypes in both H-CSS and TCGA-BRCA cohorts, and the combined analysis of all miR-200 family members demonstrated a slight predictive accuracy on H-CSS cancer specific survival at 12 years (survival c-statistic: 0.646; 95%CI 0.538-0.754).

11.
Cell Transplant ; 30: 963689721991477, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33522308

RESUMO

TRANSLATIONAL RELEVANCE: No prophylactic treatments for COVID-19 have been clearly proven and found. In this pandemic context, cancer patients constitute a particularly fragile population that would benefit the best from such treatments, a present unmet need. TMPRSS2 is essential for COVID-19 replication cycle and it is under androgen control. Estrogen and androgen receptor dependent cues converge on TMPRSS2 regulation through different mechanisms of action that can be blocked by the use of hormonal therapies. We believe that there is enough body of evidence to foresee a prophylactic use of hormonal therapies against COVID-19 and this hypothesis can be easily tested on cohorts of breast and prostate cancer patients who follow those regimens. In case of pandemic, if the protective effect of hormonal therapies will be proven on cancer patients, the use of specific hormonal therapies could be extended to other oncological groups and to healthy individuals to decrease the overall risk of infection by SARS-CoV-2.Given the COVID-19 coronavirus emergency, a special focus is needed on the impact of this rapidly spreading viral infection on cancer patients. Androgen receptor (AR) signaling in the transmembrane protease serine 2 (TMPRSS2) regulation is emerging as an important determinant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) susceptibility. In our study, we analyzed AR and TMPRSS2 expression in 17,352 normal and 9,556 cancer tissues from public repositories and stratified data according to sex and age. The emerging picture is that some patient groups may be particularly susceptible to SARS-CoV-2 infection and may benefit from antiandrogen- or tamoxifen-based therapies. These findings are relevant to choose proper treatments in order to protect cancer patients from concomitant SARS-CoV-2 contagion and related symptoms and put forward the idea that hormonal therapies could be used as prophylactic agents against COVID-19.


Assuntos
Antagonistas de Receptores de Andrógenos/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/complicações , COVID-19/complicações , Antagonistas de Estrogênios/uso terapêutico , Neoplasias da Próstata/complicações , Tamoxifeno/uso terapêutico , Antagonistas de Receptores de Andrógenos/farmacologia , Antineoplásicos Hormonais/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , COVID-19/tratamento farmacológico , COVID-19/metabolismo , Descoberta de Drogas , Antagonistas de Estrogênios/farmacologia , Feminino , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Receptores Androgênicos/análise , Receptores Androgênicos/metabolismo , Serina Endopeptidases/análise , Serina Endopeptidases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Tamoxifeno/farmacologia
12.
Cytopathology ; 32(4): 519-522, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33470486

RESUMO

Angiosarcoma of the thyroid is a rare and aggressive primary malignant tumour of the thyroid. We report the case of a 69-year-old woman who presented with a red and sore skin area at the right-anterior region of the neck. Ultrasound examination and computed tomography scan showed a non-homogeneous mass in the right thyroid lobe. Fine needle aspiration cytology was suggestive of atypical vascular proliferation and so the patient underwent right thyroid lobectomy. The specimen measured 6 × 5 × 2.5 cm, and a reddish nodule was found, including a whitish central area of maximum 4 cm in diameter. Immunohistochemistry showed CD31 and ERG positivity, while thyroglobulin, calcitonin and TTF-1 expression were negative, indicating a diagnosis of angiosarcoma.

13.
Pathol Res Pract ; 218: 153344, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33486318

RESUMO

The aim of our study was to assess the quality of Tanzanian cervical cancer specimens, evaluating telomerase alterations and human papilloma virus (HPV) infection in relation to histopathological characteristics since these biomarkers are not routinely analyzed. Thirty-two Tanzanian women with invasive cervical cancer were included in the study. Histopathological classification and all the analyses on tissue, including TERT immunohistochemistry, were performed at IRST IRCCS (Meldola, Italy). HPV typization was performed by pyrosequencing. FHACT™ was used to identify chromosomal aberrations. Nonparametric ranking statistics were used. The majority (75 %) of the cases analyzed were squamous carcinoma, while 12.5 % were adenocarcinoma. The presence of HPV infection was confirmed in 26/27 (96.3 %) cases. A high percentage of patients (88 %) were infected with HPV16 of whom 12 (44.4 %) with African type 1, and 4 (14.8 %) with African type 2. TERT expression evaluated in the entire case series showed a median H-score of 130 (range 3-270), with only one negative case. 88 % of the FISH-evaluable samples showed an amplification of the chromosomal region 3q26 (TERC) and/or 5p15, and 20q13, associated with a higher median expression of TERT (P = 0.0226). Despite pre-analytical problems in terms of sample fixation, we showed that the search for biomarkers such as HPV and telomerase is feasible in Tanzanian tissue. These markers could be important risk-stratification tools in this population.

14.
Panminerva Med ; 63(1): 37-45, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32955187

RESUMO

INTRODUCTION: Multiple myeloma (MM) is a hematological malignancy in which patients present with bone marrow infiltration of clonal terminally-differentiated plasma cells. Monoclonal protein in the serum and/or urine is frequently detected. Over the past decade, important progress has been made in the comprehension of disease biology and treatment personalization. Much work has been put into the development of chimeric antigen receptor (CAR) gene-modified T-cell therapy thought to be a promising therapeutic option for pluritreated patients with refractory MM. EVIDENCE ACQUISITION: We performed an analysis of clinical trials registered at the international repository clinicaltrials.gov using "CAR" OR "CAR T" AND "multiple myeloma" as search terms to understand what were the antigens targeted by CAR T strategies and what was the trade-off of their exploitation. The search retrieved a list of 103 trials that was manually filtered to eliminate follow-up and observational or not-pertinent trials. EVIDENCE SYNTHESIS: Most studies employed anti-BCMA targeting either alone (62/94; 66%), or in combination with a second target (12/94; 13%). The second target most studied was SLAMF7 (CD319) explored by 4/94 (4%) clinical trials. Other antigens investigated and described here include: CD44v6, CD38, CD138, MUC1, CD56, CD19, Igk light chain, Lewis Y, CD229 and GPRC5D. CONCLUSIONS: Targeting an appropriate antigen(s) is the key to both safety and efficacy of CAR T approaches in MM as there is dearth of tumor-specific antigens. Most antigens tested are merely enriched on MM cells. Working with tumor-enriched antigens requires careful assessment of the balance between harm (toxicity) and benefit (disease eradication) to the patient. This review provides an up-to-date overview of the avenues that are being explored.

15.
Cell Transplant ; 29: 963689720968749, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33108902

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. One open question is whether genetics could influence the severity of symptoms. Considering the limited data on cancer patients, we analyzed public data repositories limited to investigate angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) expressions and genetic variants to identify the basis of individual susceptibility to SARS-CoV-2.Gene expression and variant data were retrieved from Tissue Cancer Genome Atlas, Genotype-Tissue Expression, and gnomAD. Differences in gene expression were tested with Mann-Whitney U-test. Allele frequencies of germline variants were explored in different ethnicities, with a special focus on ACE2 variants located in the binding site to SARS-CoV-2 spike protein.The analysis of ACE2 and TMPRSS2 expressions in healthy tissues showed a higher expression in the age class 20 to 59 years (false discovery rate [FDR] < 0.0001) regardless of gender. ACE2 and TMPRSS2 were more expressed in tumors from males than females (both FDR < 0.0001) and, opposite to the regulation in tissues from healthy individuals, more expressed in elderly patients (FDR = 0.005; FDR < 0.0001, respectively). ACE2 and TMPRSS2 expressions were higher in cancers of elderly patients compared with healthy individuals (FDR < 0.0001). Variants were present at low frequency (range 0% to 3%) and among those with the highest frequency, the variant S19P belongs to the SARS-CoV-2 spike protein binding site and it was exclusively present in Africans with a frequency of 0.2%.The mechanisms of ACE2 and TMPRSS2 regulation could be targeted for preventive and therapeutic purposes in the whole population and especially in cancer patients.Further studies are needed to show a direct correlation of ACE2 and TMPRSS2 expressions in cancer patients and the incidence of COVID-19.


Assuntos
Infecções por Coronavirus/patologia , Predisposição Genética para Doença , Neoplasias/patologia , Peptidil Dipeptidase A/genética , Pneumonia Viral/patologia , Serina Endopeptidases/genética , Adulto , Grupo com Ancestrais do Continente Africano/genética , Enzima de Conversão de Angiotensina 2 , Betacoronavirus/isolamento & purificação , Sítios de Ligação , COVID-19 , Estudos de Casos e Controles , Infecções por Coronavirus/virologia , Bases de Dados Genéticas , Feminino , Frequência do Gene , Variação Genética , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/genética , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/virologia , SARS-CoV-2 , Serina Endopeptidases/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo , Adulto Jovem
16.
Front Oncol ; 10: 1486, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32974178

RESUMO

Women with a diagnosis of ductal carcinoma in situ (DCIS) have a high risk of developing a second breast event (SBE). The immune system might play a role in trying to prevent a SBE. Patients diagnosed with DCIS were identified in the population-based cancer registry of Area Vasta Romagna from 1997 to 2010. Median follow-up is 8.5 years. Tumor-infiltrating lymphocytes (TILs) were evaluated both in index DCIS and in SBE. The main endpoint was to assess the association between TILs' levels in index DCIS and risk of a SBE. Out of 496 DCIS patients, 100 SBEs (20.2%) were identified: 55 ipsilateral (11.1%) and 43 contralateral (8.7%). The distribution of TILs was heterogeneous, but significantly associated with grade, necrosis, screen detection and type of surgery. Patients stratified according to TILs percentage (≤5% and >5%) did not show a statistically significant difference in the 5-year cumulative incidence of SBEs: 14.9% (95% CI 11.3-19.1) and 11.0% (95% CI, 6.9-16.2), respectively (p = 0.147). In the subgroup of patients who did not receive radiotherapy, TILs >5% were associated with a reduced risk of SBE (HR 0.34, 95% CI 0.14-0.82, p = 0.016). Although we did not find any significant association between TILs and SBE, further studies evaluating their role according to radiotherapy are warranted.

17.
Front Oncol ; 10: 1415, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32903519

RESUMO

miR-155-5p is a well-known oncogenic microRNA, showing frequent overexpression in human malignancies, including breast cancer. Here, we show that high miR-155-5p levels are associated with unfavorable prognostic factors in two independent breast cancer cohorts (CSS cohort, n = 283; and TCGA-BRCA dataset, n = 1,095). Consistently, miR-155-5p results as differentially expressed in the breast cancer subgroups identified by the surrogate molecular classification in the CSS cohort and the PAM50 classifier in TCGA-BRCA dataset, with the TNBC and HER2-amplified tumors carrying the highest levels. Since the analysis of TCGA-BC dataset also demonstrated a significant association between miR-155-5p levels and the presence of mutations in homologous recombination (HR) genes, we hypothesized that miR-155-5p might affect cell response to the PARP-1 inhibitor Olaparib. As expected, miR-155-5p ectopic overexpression followed by Olaparib administration resulted in a greater reduction of cell viability as compared to Olaparib administration alone, suggesting that miR-155-5p might induce a synthetic lethal effect in cancer cells when coupled with PARP-1-inhibition. Overall, our data point to a role of miR-155-5p in homologous recombination deficiency and suggest miR-155-5p might be useful in predicting response to PARP1 inhibitors in the clinical setting.

18.
Diagn Pathol ; 15(1): 109, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32917222

RESUMO

Kang and colleagues evaluated on a case series of 1848 breast cancer (BC) patients operated for a first primary ER positive HER2 negative BC if Ki67 expression is a significant prognostic factor only when PgR expression is low. The authors concluded that Ki67 with 10% cut off value is a prognostic factor only under low PgR expression level in early BC. We would like to underline, that as already stated in our previous papers, we believe that proliferation is important to define the decision-making of adjuvant therapies in early BC. The issue on Ki67 detection is the poor reproducibility due to different antibody clones, platforms and scoring methods. Not less important is that different Ki67 cut off values have been used by San Gallen guidelines and changed overtime. Then, despite the interesting results, we believe it would be better to use Ki67 biomarker in according to the standard Ki67 cut off according to San Gallen guidelines. Nowadays, standardization and optimization of Ki67 is still an urgent need.

19.
Cell Transplant ; 29: 963689720950209, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32907382

RESUMO

Chronic lymphocytic leukemia (CLL), with an incidence rate between 4 and 6 cases per 100,000 persons per year, is considered the most prevalent leukemia in the western world. Chemoimmunotherapy (such as fludarabine, cyclophosphamide, and rituximab), bendamustine plus rituximab, and, more recently, novel agents such as ibrutinib (Bruton tyrosine kinase inhibitor), idelalisib (phosphatidylinositol-3-kinase δ inhibitor), and venetoclax (BCL-2 inhibitor) have changed the management of CLL. Shanafelt and colleagues compared the efficacy of ibrutinib-rituximab with that of standard chemoimmunotherapy in patients with treatment-naïve CLL. They did not, however, mention that the therapy varies on the basis of where patients live and, given that local guidelines not immediately reflect US Food and Drug Administration (FDA) updates, discrepancies in treatment occur. Important CLL goals are the availability of rapidly reproducible tests, standardization of national and international guidelines, and FDA approval-based treatment reimbursement.


Assuntos
Adenina/análogos & derivados , Imunoterapia , Leucemia Linfocítica Crônica de Células B/imunologia , Leucemia Linfocítica Crônica de Células B/terapia , Piperidinas/uso terapêutico , Rituximab/uso terapêutico , Adenina/uso terapêutico , Humanos , Prognóstico
20.
Int J Mol Sci ; 21(16)2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32806665

RESUMO

Microbial communities and human cells, through a dynamic crosstalk, maintain a mutualistic relationship that contributes to the maintenance of cellular metabolism and of the immune and neuronal systems. This dialogue normally occurs through the production and regulation of hormonal intermediates, metabolites, secondary metabolites, proteins, and toxins. When the balance between host and microbiota is compromised, the dynamics of this relationship change, creating favorable conditions for the development of diseases, including cancers. Microbiome metabolites can be important modulators of the tumor microenvironment contributing to regulate inflammation, proliferation, and cell death, in either a positive or negative way. Recent studies also highlight the involvement of microbiota metabolites in inducing epithelial-mesenchymal transition, thus favoring the setup of the metastatic niche. An investigation of microbe-derived metabolites in "liquid" human samples, such as plasma, serum, and urine, provide further information to clarify the relationship between host and microbiota.


Assuntos
Progressão da Doença , Metaboloma , Microbiota , Neoplasias/microbiologia , Neoplasias/patologia , Animais , Humanos , Metástase Neoplásica , Microambiente Tumoral
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...