29 research outputs found
A Modified Intraoral Resin Mouthguard to Prevent Self-Mutilations in Lesch-Nyhan Patients
Lesch-Nyhan syndrome, described in 1964 by Lesch and Nyhan, is a X-linked recessive disorder, occurring in 1 : 100000 to 1 : 380000 live births. LNS is characterized by a decrease in activity of hypoxanthine guanine phosphoribosyl transferase, an enzyme involved in purine metabolism, resulting in overproduction of uric acid. Hyperuricemia and neurological features including choreoathetoid spasticity, self-mutilation, and mental retardation clinically characterize this syndrome. In LNS patients the typical feature is loss of tissue from biting themselves with partial or complete amputation of fingers, lips, and tongue. The self-mutilation compares with the eruption of the deciduous teeth. Several drugs trials have been administered to improve self-destructive behavior and invasive treatment approaches, such as extractions of teeth and orthognathic surgery, have been suggested with variable effectiveness. Nowadays prevention is, therefore, the standard of care. The role of dentistry is essential in the management of the self-mutilating behavior, because the teeth represent the main self-injury instrument. This report presents a revision of various therapeutic approaches to manage self-destruction, highlighting the effectiveness of a preventive treatment. It describes a new technique: a resin mouthguard, realized at Gaslini Hospital, to obtain immediate healing of the oral lesions, confirmed in the follow-up period
Mudanças religiosas e dinâmicas demográficas: mais além da teoria da secularização. O caso do catolicismo na cidade de Córdoba, Argentina
Este artículo explora críticamente las explicaciones de las dinámicas religiosas en Argentina basadas en la Teoría de la Secularización (TdS). La mayoría de sus referentes usa como variable independiente las relaciones político-institucionales; por eso, la TdS explica lo que sucede con la dirigencia de la institución y las organizaciones intermedias. Esta investigación recoge datos directos de los registros de bautismos durante un siglo en la ciudad de Córdoba (Argentina) y los compara con la tasa de natalidad. Este análisis muestra que eluso de variables político-institucionales no explica adecuadamente lo que sucede con las dinámicas religiosas, medidas en bautismos. La hipótesis propuesta es que las transformaciones religiosas se entienden mejor cuando se aplican variables demográficas.his article critically explores the explanations of religious dynamics in Argentina based on Secularization Theory (TdS). Most scholarship uses political-institutional relations as an independent variable; therefore, TdS focuses on what takes place within the leadership of the institution and intermediate organizations. This research collects data directly from a century of baptism records in the city of Córdoba (Argentina) and compares it with the city’s birth rate. This analysis shows that the use of political-institutional variables fails to adequately explain religious dynamics, as measured in baptisms. The proposed hypothesis is that religious transformations are better understood when demographic variables are applied.Este artigo explora criticamente as explicações das dinâmicas religiosas na Argentina baseadas na Teoria da Secularização (TdS). A maioria de seus referentes usa as relações político-institucionais como variável independente; por isso, a TdS explica o que acontece com a direção da instituição e das organizações intermediárias. Esta pesquisa recolhe dados diretos dos registros de batismos durante um século na cidade de Córdoba (Argentina) e os compara com a taxa de natalidade. Essa análise mostra que o uso de variáveis político-institucionais não explica adequadamente o que acontece com as dinâmicas religiosas, medidas em batismos. A hipótese proposta é que as transformações religiosas são melhor entendidas quando variáveis demográficas são aplicadas.Fil: Morello SJ, Gustavo. Boston College; Estados UnidosFil: Rabbia, Hugo Hernán. Universidad Nacional de Córdoba. Instituto de Investigaciones Psicológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Psicológicas; Argentina. Universidad Católica de Córdoba. Facultad de Ciencias Politicas y Relaciones Internacionales; Argentin
Delayed response to maintenance therapy after first-line chemotherapy in metastatic intrahepatic cholangiocarcinoma: A case report
BACKGROUND:
Intrahepatic cholangiocarcinoma is an aggressive tumor originating in the epithelium of the bile duct, often associated with distant dissemination. The prognosis is poor and treatment is challenging due to low response rate to standard chemotherapy and lack of targeted therapies.
CASE PRESENTATION:
Here we report the case of a 74-year-old white woman affected by intrahepatic cholangiocarcinoma with metastatic involvement of spleen, lung, peritoneum, and intra-abdominal lymph nodes. As first-line chemotherapy, she was given cisplatin-gemcitabine chemotherapy. The treatment was well tolerated with the exception of grade 1 constipation and a single episode of grade 4 thrombocytopenia occurring after the fourth course. After the first three courses of chemotherapy a computed tomography scan evaluation demonstrated no change; her CA19-9 levels were slightly decreased. However, after the sixth course of chemotherapy a computed tomography scan revealed a dimensional enlargement of the lung metastases; her CA19-9 levels increased. She was then treated with gemcitabine alone. After 2 months of gemcitabine monotherapy a significant regression of lung and spleen metastases, as well a CA19-9 level reduction, occurred. Eight months after the start of gemcitabine monotherapy no signs of progression were reported.
CONCLUSIONS:
Treatment of metastatic intrahepatic cholangiocarcinoma with gemcitabine as maintenance therapy after first-line chemotherapy could be continued until clear evidence of disease progression since delayed responses are possible
RET rearrangements in non-small cell lung cancer: Evolving treatment landscape and future challenges
The Rearranged during Transfection (RET) oncogene has been extensively investigated in solid malignancies, particularly thyroid cancer and non-small cell lung cancer (NSCLC), and represents an attractive therapeutic target. RET rearrangements occur in 1-2% of lung adenocarcinomas, where they function as potent oncogenic drivers. Importantly, tumors harboring RET fusions are particularly sensitive to RET tyrosine kinase inhibitors. Results of the LIBRETTO-001 and ARROW clinical trials led to the approval of novel potent and selective RET inhibitors, selpercatinib and pralsetinib, able to overcome the limits of previously used multikinase inhibitors. Herein, we review the most relevant evidences about the role of RET signaling in NSCLC. In addition, we interrogated the Project GENIE database to investigate common clinical and molecular features of RET-fusion positive NSCLC. This analysis revealed that RET rearrangements occurred more frequently in younger and light smoker patients and were associated with a lower tumor mutational burden, compared to RET-fusion negative tumors. Moreover, we assessed and described the differences between RET genomic alterations in NSCLC and thyroid cancers. Finally, we summarized how the treatment landscape of RET-rearranged NSCLC has changed in the last few years, which are the available data about the recognized mechanisms of resistance to RET inhibitors and the challenges for future development of novel therapeutic strategies, aiming to improve management of patients with RET-fusion positive NSCLC
Health-related quality of life is underestimated and underreported in phase III clinical trials in NSCLC
Major associations of medical oncologists remark that novel anticancer treatments should guarantee improvement of survival outcomes as well as of patients' quality of life (QoL). Herein, we investigated QoL assessment and reporting in phase III randomized controlled trials (RCTs) testing new drugs in metastatic non-small cell lung cancer (NSCLC), published between 2010 and 2021. We selected 172 RCTs for further analysis. Only 2/172 (1.2%) trial included QoL among primary study endpoints. Of note, 40/172 (23.3%) trials did not include QoL assessment among endpoints. The majority of RCTs (102/172, 59.3%) did not report QoL results in primary publications. Particularly, RCTs testing immunotherapy, target therapy and chemotherapy did not disclose QoL data in primary publications in 97.0%, 51.5% and 46.5% of cases, respectively. Next, we found that only 43/95 (45.3%) positive studies reported QoL results in primary articles. Of the 102 trials missing QoL data in primary manuscripts, only 21 (20.6%) disclosed QoL results in a secondary publication. Finally, we found a common fail in adherence to CONSORT-PROs items in publications reporting QoL results. In summary, our study reveals a relevant inadequate assessment and under-reporting of QoL in RCTs of novel systemic treatments for patients with metastatic NSCLC
Role of FGFR3 in bladder cancer: Treatment landscape and future challenges
: Bladder cancer is a heterogeneous malignancy and is responsible for approximately 3.2% of new diagnoses of cancer per year (Sung et al., 2021). Fibroblast Growth Factor Receptors (FGFRs) have recently emerged as a novel therapeutic target in cancer. In particular, FGFR3 genomic alterations are potent oncogenic drivers in bladder cancer and represent predictive biomarkers of response to FGFR inhibitors. Indeed, overall ∼50% of bladder cancers have somatic mutations in the FGFR3 -coding sequence (Cappellen et al., 1999; Turner and Grose, 2010). FGFR3 gene rearrangements are typical alterations in bladder cancer (Nelson et al., 2016; Parker et al., 2014). In this review, we summarize the most relevant evidence on the role of FGFR3 and the state-of-art of anti-FGFR3 treatment in bladder cancer. Furthermore, we interrogated the AACR Project GENIE to investigate clinical and molecular features of FGFR3-altered bladder cancers. We found that FGFR3 rearrangements and missense mutations were associated with a lower fraction of mutated genome, compared to the FGFR3 wild-type tumors, as also observed in other oncogene-addicted cancers. Moreover, we observed that FGFR3 genomic alterations are mutually exclusive with other genomic aberrations of canonical bladder cancer oncogenes, such as TP53 and RB1. Finally, we provide an overview of the treatment landscape of FGFR3-altered bladder cancer, discussing future perspectives for the management of this disease
Analysis of phase III clinical trials in metastatic NSCLC to assess the correlation between QoL results and survival outcomes
Abstract Background In addition to improving survival outcomes, new oncology treatments should lead to amelioration of patients’ quality of life (QoL). Herein, we examined whether QoL results correlated with PFS and OS outcomes in phase III randomized controlled trials (RCTs) investigating new systemic treatments in metastatic non-small cell lung cancer (NSCLC). Methods The systematic search of PubMed was conducted in October 2022. We identified 81 RCTs testing novel drugs in metastatic NSCLC and published in the English language in a PubMed-indexed journal between 2012 and 2021. Only trials reporting QoL results and at least one survival outcome between OS and PFS were selected. For each RCT, we assessed whether global QoL was “superior,” “inferior,” or with “non-statistically significant difference” in the experimental arm compared to the control arm. Results Experimental treatments led to superior QoL in 30 (37.0%) RCTs and inferior QoL in 3 (3.7%) RCTs. In the remaining 48 (59.3%) RCTs, a statistically significant difference between the experimental and control arms was not found. Of note, we found a statistically significant association between QoL and PFS improvements (X 2 = 3.93, p = 0.0473). In more detail, this association was not significant in trials testing immunotherapy or chemotherapy. On the contrary, in RCTs testing target therapies, QoL results positively correlated with PFS outcomes (p = 0.0196). This association was even stronger in the 32 trials testing EGFR or ALK inhibitors (p = 0.0077). On the other hand, QoL results did not positively correlate with OS outcomes (X 2 = 0.81, p = 0.368). Furthermore, we found that experimental treatments led to superior QoL in 27/57 (47.4%) trials with positive results and in 3/24 (12.5%) RCTs with negative results (p = 0.0028). Finally, we analyzed how QoL data were described in publications of RCTs in which QoL outcomes were not improved (n = 51). We found that a favorable description of QoL results was associated with sponsorship by industries (p = 0.0232). Conclusions Our study reveals a positive association of QoL results with PFS outcomes in RCTs testing novel treatments in metastatic NSCLC. This association is particularly evident for target therapies. These findings further emphasize the relevance of an accurate assessment of QoL in RCTs in NSCLC
1599P - Effects of Hedgehog signaling inhibition on epithelial-stromal interactions in triple negative breast cancer cells
Abstract
Aim
Triple-negative breast cancer (TNBC) is a group of tumors that do not express HER2, estrogen and progesterone receptors. Due to reduced response to conventional antitumor therapies and poor prognosis, new targeted agents are needed for such aggressive sub-type of breast cancer. Multiple lines of evidence support the idea that deregulation of Hedgehog (Hh) signaling has a role in the pathogenesis of breast cancer, in part through the promotion of epithelial-stromal interactions. Therefore, the inhibition of the Hh pathway has been proposed as an interesting therapeutic approach
Methods
The main objective of this study is to investigate the role of Hh signaling pathway in TNBC. To this aim, we used a panel of human breast cancer cell lines, including five cancer cells lines positive for ER, PR and HER2 expression (nTNBC) and five Triple Negative Breast Cancer cell lines (TNBC). The effects induced by the Smo-inhibitor NVP-LDE225 on proliferation, angiogenesis and signal transduction of breast cancer cells were investigated
Results
GLI1, one of the major transcription factors induced by Hh signaling activation, is more expressed in TNBC than in nTNBC cell lines. Consistently, NVP-LDE225 treatment induced a more pronounced inhibitory effect on TNBC, in terms of tumor growth: while nTNBC cells display an IC50 of∼5mM, TNBC cell lines are more sensitive, with an average IC50 of∼2mM. In addition, Hh inhibition caused a robust impairment of TNBC cells invasion capabilities. These effects are coupled with a strong inhibition of VEGFA production by both tumor and stromal cells (human fibroblasts and HUVECs). Accordingly, NVP-LDE225 treatment interfered with HUVEC capillary tube formation, an effect even more evident than that observed with bevacizumab, the only targeted agent approved to date for TNBC patients
Conclusions
Our results suggest that Hh has a specific role in breast epithelial-stromal interactions by regulation of angiogenesis. An orthotopic in vivo experiment in nude mice xenografted with TNBC cells, testing the combination of NVP-LDE225 with bevacizumab, is ongoing
Disclosure
All authors have declared no conflicts of interest
Neoadjuvant Treatment in Locally Advanced Pancreatic Cancer (LAPC) Patients with FOLFIRINOX or Gemcitabine NabPaclitaxel: A Single-Center Experience and a Literature Review
The optimal therapeutic strategy for locally advanced pancreatic cancer patients (LAPC) has not yet been established. Our aim is to evaluate how surgery after neoadjuvant treatment with either FOLFIRINOX (FFN) or Gemcitabine-NabPaclitaxel (GemNab) affects the clinical outcome in these patients. LAPC patients treated at our institution were retrospectively analysed to reach this goal. The group characteristics were similar: 35 patients were treated with the FOLFIRINOX regimen and 21 patients with Gemcitabine Nab-Paclitaxel. The number of patients undergoing surgery was 14 in the FFN group (40%) and six in the GemNab group (28.6%). The median Disease-Free Survival (DFS) was 77.10 weeks in the FFN group and 58.65 weeks in the Gem Nab group (p = 0.625), while the median PFS in the unresected group was 49.4 weeks in the FFN group and 30.9 in the GemNab group (p = 0.0029, 95% CI 0.138–0.862, HR 0.345). The overall survival (OS) in the resected population needs a longer follow up to be completely assessed, while the median overall survival (mOS) in the FFN group was 72.10 weeks and 53.30 weeks for the GemNab group (p = 0.06) in the unresected population. Surgery is a valuable option for LAPC patients and it is able to induce a relevant survival advantage. FOLFIRINOX and Gem-NabPaclitaxel should be offered as first options to pancreatic cancer patients in the locally advanced setting