1,721,032 research outputs found
NUT midline carcinoma of the head and neck: current perspectives
Full text linkNUT midline carcinoma (NMC) is a rare and aggressive subtype of squamous carcinoma that typically arises from midline supradiaphragmatic structures, frequently from the head and neck area. NMC is genetically driven by a chromosomal rearrangement involving the NUT gene, which forms oncoproteins considered major pathogenic drivers of cellular transformation. Diagnosis of NMC has been made remarkably easier with the availability of a commercial antibody against NUT, and can be established through positive nuclear immunohistochemical staining. Although NMC remains an underrecognized malignancy, in recent years there has appeared to be increasing awareness of disease and frequency of diagnosis in adults. To date, a standard treatment for head and neck NMC has not been established and a multimodal approach with systemic chemotherapy, surgery and radiation therapy is currently adopted in clinical practice. Recently, BET inhibitors and histone deacetylase inhibitors have emerged as two promising classes of targeted agents, currently investigated in clinical trials for adults with head and neck NMC. At the same time, combination approaches and novel targeted agents, such as next-generation BET inhibitors and CDK9 inhibitors, have shown preclinical activity. The present review explores the clinical pathological characteristics of NMC of the head and neck and presents the current state of the art on diagnosis, prognosis, and treatment of this rare but lethal disease
Hereditary Ovarian Cancer: Not Only BRCA 1 and 2 Genes
Full text linkMore than one-fifth of ovarian tumors have hereditary susceptibility and, in about 65–85% of these cases, the genetic abnormality
is a germline mutation in BRCA genes. Nevertheless, several other suppressor genes and oncogenes have been associated with
hereditary ovarian cancers, including the mismatch repair (MMR) genes in Lynch syndrome, the tumor suppressor gene, TP53, in
the Li-Fraumeni syndrome, and several other genes involved in the double-strand breaks repair system, such as CHEK2, RAD51,
BRIP1, and PALB2. The study of genetic discriminators and deregulated pathways involved in hereditary ovarian syndromes is
relevant for the future development ofmolecular diagnostic strategies and targeted therapeutic approaches.The recent development
and implementation of next-generation sequencing technologies have provided the opportunity to simultaneously analyzemultiple
cancer susceptibility genes, reduce the delay and costs, and optimize the molecular diagnosis of hereditary tumors. Particularly, the
identification of mutations in ovarian cancer susceptibility genes in healthy women may result in a more personalized cancer risk
management with tailored clinical and radiological surveillance, chemopreventive approaches, and/or prophylactic surgeries. On
the other hand, for ovarian cancer patients, the identification of mutations may provide potential targets for biologic agents and
guide treatment decision-making
Twenty-years experience with de novo metastatic breast cancer
No full textAlthough new treatments have been widely studied to improve the survival of patients with metastatic breast cancer (BC), prognosis continues to be poor with an average survival time no longer than 3 years. We carried on a population-based study with the purpose of evaluating the outcome of metastatic breast cancer in the province of Modena from 1990 to 2009. We examined the Modena Cancer Registry and evaluated the 5-year overall survival (OS) of women diagnosed with a de novo metastatic breast cancer between 1990 and 2009, defining 5 periods of 4 years each. After a median follow-up time of 29 months, the 5-year OS was 11% for years 1990-1993, 15% for years 1994-1997, 12% for years 1998-2001, 20% for years 2002-2005 and 29% for years 2006-2009 (p = 0.012). Overall, although no OS differences were noted in the first decade analyzed, a real advantage has been shown in the last two cohorts. In a multivariate analysis, the 5-year OS was significantly increased only for hormone receptor positive and HER2+ tumors, whereas chemotherapy treatments were not significant independent predictors of survival in "de novo" metastatic BC (p = 0.08). Our analysis confirms that the prognosis of de novo metastatic breast cancer has improved overtime, particularly in the last decade. Trastuzumab, LH-RH analogues and aromatase inhibitors have determined a significant clinical benefit and cost-effectiveness in metastatic breast cancer treatment
The Association between Endometriomas and Ovarian Cancer: Preventive Effect of Inhibiting Ovulation and Menstruation during Reproductive Life
Full text linkAlthough endometriosis frequently involves multiple sites in the pelvis, malignancies associated with this disease are mostly
confined to the ovaries, evolving from an endometrioma. Endometriomas present a 2-3-fold increased risk of transformation
in clear-cell, endometrioid, and possibly low-grade serous ovarian cancers, but not in mucinous ovarian cancers. These last
cancers are, in some aspects, different from the other epithelial ovarian cancers, as they do not appear to be decreased by the
inhibition of ovulation and menstruation.The step by step process of transformation fromtypical endometrioma, through atypical
endometrioma, finally to ovarian cancer seems mainly related to oxidative stress, inflammation, hyperestrogenism, and specific
molecular alterations. Particularly, activation of oncogenic KRAS and PI3K pathways and inactivation of tumor suppressor genes
PTEN and ARID1A are suggested as major pathogenic mechanisms for endometriosis associated clear-cell and endometrioid
ovarian cancer. Both the risk for endometriomas and their associated ovarian cancers seems to be highly and similarly decreased
by the inhibition of ovulation and retrograde menstruation, suggesting a common pathogenetic mechanism and common possible
preventive strategies during reproductive life
Impressive response to dose-dense chemotherapy in a patient with NUT midline carcinoma
No full textObjective: Rare disease
Background: NUT midline carcinoma (NMC) is a rare, highly lethal malignancy that results from a chromosome translocation and mostly arises in the midline organs. To date, no treatment has been established. Most patients receive combinations of chemotherapy regimens and radiation, and occasionally subsequent resection; nevertheless, patients have an average survival hardly exceeding 7 months.
Case Report: A 21-year-old patient was admitted to our division with a large mediastinal mass with lung nodules, multiple vertebral metastases, and massive nodal involvement. In a few days, the patient developed a superior vena cava syndrome and an acute respiratory failure. Due to the rapid course of the disease, based on preliminary histology of poorly differentiated carcinoma, a dose-dense biweekly chemotherapy with paclitaxel, ifosfamide, and cisplatin was started. In the meantime, the diagnosis of NMC was confirmed. A surprising clinical benefit was obtained after the first cycle of chemotherapy, and after 6 cycles a PET-CT scan showed a very good response. At this point, radiotherapy was started but the disease progressed outside of the radiation field. The patient entered into a compassionate use protocol with Romidepsin, but a PET/CT scan after the first course showed disease progression with peritoneal and retroperitoneal carcinosis. A treatment with Pemetrexed was then started but the patient eventually died with rapid progressive disease.
Conclusions: Our case history adds some interesting findings to available knowledge: NMC can be chemosensitive and radiosensitive. This opens the possibility to study more aggressive treatments, including high-dose consolidation chemotherapy and to evaluate the role of biological agents as maintenance treatments
Interstitial Lung Disease in Abemaciclib-treated Patients during SARS-CoV-2 Pandemic: A Case Series.
Full text linkAbemaciclib is a cyclin-dependent 4/6 inhibitor approved by FDA in 2017 and by EMA in 2018 for
treatment of hormone receptors positive, HER2 negative metastatic breast cancer in association
with endocrine therapy. In 2019 FDA warned for a rare but severe lung inflammation possibly
related to CDK 4/6 inhibitors. At the end of 2019 the world comes to know to a new corona virus
causing potential fatal lung injury. Here we report three different cases of interstitial lung disease in
patients treated with Abemaciclib during SARS-CoV-2 pandemic at Modena Cancer Center
Acceptability and adherence in a chemoprevention trial among women at increased risk for breast cancer attending the modena familial breast and ovarian cancer center (Italy)
No full textChemoprevention for women at risk for breast cancer has been shown to be effective, but in actual practice, women's uptake of chemoprevention has been poor. We explored factors that influence acceptability, adherence, and dropout in the International Breast (Prevention) Intervention Study during our first 3 years of activity at the Modena Familial Breast and Ovarian Cancer Center. We evaluated socio-demographic characteristics, health status, adherence, and side effect intensity. Semi-structured interviews analyzed reasons for accepting/refusing/stopping the trial. A total of 471 postmenopausal women were invited to participate, of which 319 declined to participate (68%), 137 accepted to participate (29%), and 15 participants did not make a final decision (3%). Breast cancer-related worries and trust in our preventive and surveillance programs were the most frequent reasons for accepting. Side effect-related worry was the most frequent reason for refusing. General practitioners' and family members' opinions played an important role in the decision-making process. Adherence significantly decreased after a 12-month follow-up, but it remained unchanged after 24- and 36-month follow-ups. Mild/moderate side effects reported by women did not change after 12 months of treatment. Forty percent of women withdrew from the study due to complaints of side effects. We concluded that chemoprevention trials are difficult medical experiments and that the process of deciding about whether or not to participate is based mainly on beliefs and values. This study has important clinical implications. During counselling with prospective participants, it is important to emphasize the potential benefits and to promote an informed choice. How participants make decisions, their belief systems, and their perception of risk are all factors that should be investigated in future research
- …
