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Radiotherapy (RT) may have a cardiotoxic effect on the heart and cardiovascular system. Postulated mechanisms mediating these complications include vascular endothelium damage and myocardial fibrosis. The aim of our study was to assess endothelial damage and myocardial fibrosis in the early period after RT on the basis of cardiac biomarkers and in relation to the radiation dose applied to individual heart structures in patients treated for non-small-cell lung cancer. This single-center prospective study included consecutive patients with lung cancer (LC) who were referred for treatment with radiochemotherapy (study group) or chemotherapy (control group). The study protocol included performing an echocardiographic examination, a standard ECG examination, and collecting blood samples for laboratory tests before starting treatment for lung cancer in the first week after completing RT (after four cycles of chemotherapy in the control group) and after 12 weeks from the end of treatment. The study included 23 patients in the study group and 20 patients in the control group. Compared to the baseline values, there was a significant increase in total cholesterol concentration in the study group immediately after the end of RT, which persisted for three months after the end of therapy. After taking into account the use of statins in the analysis, it was found that an increase in total cholesterol concentration after oncological treatment was observed only among patients who did not use statins. Taking into account the assessment of myocardial fibrosis markers, there were no significant changes in the concentration of matrix metallopeptidase 9 (MMP-9) and tissue inhibitors of metalloproteinases 1 (TIMP-1) in the study group. In patients treated with radiochemotherapy, there was a significant increase in the concentration of intercellular adhesion molecule 1 (ICAM-1) immediately after RT, when compared to the baseline. After taking into account the use of statins, an increase in ICAM-1 concentration immediately after RT was observed only in patients who did not use statins. There was also a significant correlation between the radiation dose received by the left anterior descending coronary artery (LAD) and left circumferential coronary artery, and vascular cell adhesion protein 1 (VCAM-1) concentration measured at three months after the end of RT. Immediately after completion of radiotherapy, a significant increase in the level of ICAM-1 is observed indicating endothelial damage. The radiation dose to coronary arteries should be minimized, as it correlates with the concentration of VCAM-1. The use of statins may prevent the increase in total cholesterol and ICAM-1 concentration after irradiation for lung cancer; however, further studies designed for this specific purpose are necessary to confirm the effectiveness of statins in this area.
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Fibrose , Neoplasias Pulmonares , Humanos , Masculino , Feminino , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Endotélio Vascular/efeitos da radiação , Endotélio Vascular/patologia , Endotélio Vascular/metabolismo , Endotélio Vascular/efeitos dos fármacos , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/sangue , Miocárdio/patologia , Miocárdio/metabolismo , Radioterapia/efeitos adversos , Inibidor Tecidual de Metaloproteinase-1/sangue , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Cardiomiopatias/etiologia , Cardiomiopatias/patologia , Colesterol/sangue , Biomarcadores/sangueRESUMO
Oxygen balance is crucial for angiogenesis, immunity, and tissue repair. The human oviduct is essential for reproductive function, and any imbalance in homeostasis leads to fertility disturbances and might be a reason for ectopic pregnancy development. Uterine myoma is a widespread benign tumour, which is often accompanied by infertility. Telocytes have been discussed in the contexts of motility, fibrosis development, and angiogenesis. We observed the oviducts from patients with and without uterine myoma, comparing the expression of HIF-1, HO, VEGF and its receptor, NOS, oestrogen, and progesterone receptors by immunolabeling. The myometrial and oviductal telocytes were also compared in both groups. Biochemical analyses were conducted for FSH, LH, AMH, sFlt, oestrogen, and progesterone in blood samples. Patients with uterine myoma have different expressions of sex steroid receptors and an increased number of telocytes. The decreasing VEFG expression was compensated by the rise in the HIF-1 and NOS expression. Blood biochemical analyses revealed a higher progesterone level and lower AMH in patients with uterine myoma. No differences in sFlt, FSH, and LF were observed. Uterine myoma impacts oviduct oxygen homeostasis and might cause fertility disturbances (uterine and oviductal infertility factors).
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Infertilidade , Leiomioma , Mioma , Telócitos , Animais , Estrogênios/metabolismo , Feminino , Hormônio Foliculoestimulante/metabolismo , Homeostase , Humanos , Hipóxia/metabolismo , Infertilidade/metabolismo , Leiomioma/metabolismo , Mioma/metabolismo , Mioma/patologia , Oviductos/metabolismo , Oxigênio/metabolismo , Gravidez , Progesterona/metabolismo , Telócitos/patologiaRESUMO
Up to 2% of pregnancies may be extrauterine. Despite reproductive problems, they might increase the risk of serious complications. We present a case report of a 31-year-old woman with two extrauterine pregnancies - tubal and ovarian, which occurred at the same side with little time difference. In addition, we aimed to examine possible reasons underlying this rare pathology. Thus, surgically removed tissue specimens were morphologically assessed and further compared with specimens from healthy control patients. Telocytes were analysed in detail due to their pivotal role in the female reproductive system. Our study had observational character and obvious limitations typical for a clinical case. Yet, such a clinical case of two ectopic pregnancies has not been previously reported in the literature.
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Gravidez Ectópica , Telócitos , Gravidez , Humanos , Feminino , Adulto , Estudos Retrospectivos , Ovário , Gravidez Ectópica/diagnóstico , Gravidez Ectópica/cirurgiaRESUMO
Lung cancer is a major cause of cancer-related mortality worldwide, both in men and women. The vast majority of patients are diagnosed with non-small-cell lung cancer (NSCLC, 80-85% of lung cancer cases). Therapeutics named immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment in the last decade. They are monoclonal antibodies, and those directed against PD-1 (programmed cell death protein 1) or PD-L1 (programmed cell death-ligand 1) have been used in the treatment of lung cancer and significantly improved the prognosis of NSCLC patients. However, during treatment with ICIs, immune-related adverse events (irAEs) can occur in any organ and any tissue. At the same time, although cardiac irAEs are relatively rare compared to irAEs in other organs, they have a high mortality rate. The two most common clinical manifestations of immunotherapy-related cardiotoxicity are myocarditis and pericarditis. Various types of arrhythmias have been reported in patients treated with ICIs, including the occurrence of life-threatening complete atrioventricular block or ventricular tachyarrhythmias. Here, we aim to summarize the incidence, clinical manifestations, underlying mechanisms, diagnosis, and treatment strategies for ICI-associated cardiotoxicity as these issues become very important in view of the increasing use of ICI in the treatment of lung cancer.
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Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cardiotoxicidade/patologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Inibidores de Checkpoint Imunológico/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Cardiotoxicidade/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/imunologia , Humanos , Inibidores de Checkpoint Imunológico/imunologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/efeitos adversos , Prognóstico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologiaRESUMO
BACKGROUND: Uterine leiomyoma is the most widespread benign tumor affecting women of childbearing age. There are still gaps in the understanding of its pathogenesis. Telocytes are unique cells found in more than 50 different locations inside the human body. The functional relationship between cells could clarify the pathogenesis of leiomyomata. Examination of membrane receptors on telocytes could explain their role in fibrosis, oxidative stress, and myometrial contractility. AIM: This research was conducted to assess the density of telocytes in terms of their putative role in leiomyoma formation by focusing on their correlation with the expression of estrogen and progesterone receptors. METHODS: For gross evaluation of uterine tissue samples from leiomyoma, routine histology of adjacent and unaffected myometrium was performed. Immunohistochemical analysis of c-kit, tryptase, CD34, PDGFRα (telocyte-specific), and ER and PRs (estrogen and progesterone receptors) was performed to examine uterine telocytes and the expression of sex steroid receptors. RESULTS: The decline in telocyte density in leiomyoma foci was correlated with high progesterone expression and low estrogen receptor expression. The unchanged myometrium showed the opposite correlation and balance between both steroid hormone receptors. The difference in sex steroid receptor expression is correlated with the density of uterine telocytes, which emphasizes their conductor function. CONCLUSIONS: A reduction in telocyte density and the changes in examined marker expression demonstrate the involvement of telocytes in local homeostasis. The expression of membrane receptors explicitly indicates their functional potential in the human myometrium, focusing attention on contractility and local homeostasis.
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Congêneres do Estradiol/farmacocinética , Leiomioma/diagnóstico por imagem , Leiomioma/patologia , Progesterona/farmacocinética , Telócitos/efeitos dos fármacos , Telócitos/fisiologia , Neoplasias Uterinas/diagnóstico por imagem , Neoplasias Uterinas/patologia , Adulto , Idoso , Congêneres do Estradiol/fisiologia , Feminino , Humanos , Pessoa de Meia-Idade , Polônia , Progesterona/fisiologiaRESUMO
PURPOSE OF REVIEW: Despite aggressive treatment based on definitive chemoradiotherapy, 5-year overall survival in unresectable stage III nonsmall cell lung cancer remains poor (15-20%). The novel immunotherapy based on immune checkpoint inhibitors (ICIs) presents as the therapeutic 'Holly Grail' in lung cancer treatment. RECENT FINDINGS: Preclinical models provide evidence of immunotherapy-radiotherapy (IM-RT) synergy. The exposure to ionizing radiation turns tumor in an in-situ vaccine, primes the innate immune system, increases immunotherapy efficacy by overcoming the immunosuppressive microenvironment of immune-resistant tumors and promotes a systemic, out-of-field antitumor T-cell-mediated response called abscopal effect. The immunomodulatory and abscopal effects of radiotherapy can be further enhanced by combining with systemic immunotherapies. The phase III START trial proved that liposomal vaccine - tecemotide (L-BLP25) administered as maintenance therapy after concurrent chemoradiotherapy (CRT) in LA-NSCLC prolongs survival. In the phase III PACIFIC trial consolidation with durvalumab, an anti-PDL-1 antibody, was associated with survival benefit in patients diagnosed with LA-NSCLC who responded to concurrent chemoradiotherapy. SUMMARY: PACIFIC trial results are expected to definitely establish durvalumab as standard consolidation strategy in LA-NSCLC. Many clinical trials are ongoing in the field of immunoradiotherapy in LA-NSCLC to define the optimal conditions for this therapeutic combination.
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Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/terapia , Imunoterapia/métodos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/terapia , Anticorpos Monoclonais/administração & dosagem , Vacinas Anticâncer/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Ensaios Clínicos Fase III como Assunto , Terapia Combinada , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Lead is toxic to humans and wildlife. Most studies of lead exposure of raptors focus on the winter, non-breeding season when they scavenge heavily. We evaluated blood lead concentrations (BLCs) of red-shouldered hawks (Buteo lineatus) during the non-scavenging season in the eastern United States. BLCs of 53 of 70 hawks were above the limit of detection ([Formula: see text] = 9.25 µg/dL ± 19.81; ± SD). Adult hawks had higher BLCs ([Formula: see text] = 12.86 µg/dL ± 24.72) than did nestlings ([Formula: see text] = 3.25 µg/dL ± 2.62; p ≤ 0.001, χ2 = 13.2). There was no difference in BLCs of adult hawks among physiographic provinces but there were differences between urban and non-urban settings (p = 0.04, χ2 = 4.2). Soils and invertebrate hawk prey also had quantifiable lead concentrations. Our work shows that red-shouldered hawks are exposed to lead when not scavenging, and suggests pathways by which these birds may be exposed.
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Cruzamento , Exposição Ambiental/análise , Poluentes Ambientais/sangue , Falcões/sangue , Chumbo/sangue , Animais , Animais Selvagens , Região dos Apalaches , Estações do Ano , Estados UnidosRESUMO
Angiogenesis is a process of development of new vessels from the preexisting vascular network of a host. This is process which is seen in many physiological situations but it accompanies also a development of different lesions, i.e. neoplasms. Uterine fibroids are one of the most frequent lesions which affect human internal female genital tracts. Authors briefly review most important pro-angiogenic factors, based on their own observation as well as reviewing current literature. They pay much attention to vascular density which is significantly changed in the uterine tumors.
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Indutores da Angiogênese/metabolismo , Leiomioma/etiologia , Miométrio/metabolismo , Neovascularização Patológica , Neoplasias Uterinas/etiologia , Útero/irrigação sanguínea , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
Uterine leiomyomata present major problem for females. Although they are benign tumors their frequency is associated with many symptoms like infertility, abdominal pain, menorrhagia. Authors based on their own morphological studies and review of the literature try to indicate main factors causing angiogenesis within leiomyomata and its influence on tumor growth. The strongest proangiogenic factor seems to be hypoxia, which stimulates up- and down-regulation of numerous genetically determined substances. Also mechanical pressure acting upon newly growing vessels is one of the factors which may determine formation of so called "vascular pseudocapsule" around the lesion.
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Indutores da Angiogênese/metabolismo , Leiomioma/irrigação sanguínea , Miométrio/irrigação sanguínea , Neoplasias Uterinas/irrigação sanguínea , Útero/irrigação sanguínea , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neovascularização Patológica , Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
Corrosion casting and scanning electron microscopy are currently best available technique which allows observation of microvascular bed of different anatomical structures and obtaining quasi 3-D pictures, necessary for reconstruction of microvessels. Application of synthetic resins, which fill practically the whole vascular bed enables profound analysis of such obtained specimens.
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Vasos Sanguíneos/ultraestrutura , Molde por Corrosão/métodos , Microscopia Eletrônica de Varredura/métodos , Útero/irrigação sanguínea , Feminino , Humanos , Microcirculação , Neovascularização Patológica/patologia , Útero/fisiologiaRESUMO
BACKGROUND: Anticancer treatment is associated with many side effects, including those involving the cardiovascular system. While many studies are available on the effects of radiotherapy (RT) on the left ventricle (LV), studies are lacking on the early effects of RT on the structure and function of the right ventricle (RV). Our study aims to assess, using modern echocardiographic techniques, the effect of irradiation on RV systolic function in the mid-term follow-up of patients undergoing RT for lung cancer (LC). METHODS: This single-center, prospective study included consecutive patients with LC who were referred for treatment with definite radiotherapy and chemotherapy (study group) or chemotherapy only (control group). RESULTS: The study included 43 patients with a mean age of 64.9 ± 8.1 years. Cancer treatment-related RV toxicity (CTR-RVT) was found in 17 patients (40%). Early reductions in TAPSE values were observed among patients in the study group (20.3 mm vs. 22.1 mm, p = 0.021). Compared to baseline, there was a significant reduction in RV global longitudinal strain (RV GLS) in the study group immediately after the treatment (-21.1% vs. -18.4%, p = 0.02) and also at 3 months after RT (-21.1% vs. -19.1%, p = 0.021). A significant reduction in the RV FWLS value was also observed at 3 months after the end of the treatment (-23.8% vs. -21.8, p = 0.046). There were no significant changes in the three-dimensional right ventricular ejection fraction (3DRVEF) during the follow-up. We found a correlation (p = 0.003) between the mean dose of radiation to the RV and 3DRVEF when assessed immediately after RT. The mean dose of radiation to the heart correlated with RV free-wall longitudinal strain (RV FWLS) immediately after RT (p = 0.03). CONCLUSIONS: RV cardiotoxicity occurs in nearly half of patients treated for lung cancer. TAPSE is an important marker of deterioration of RV function under LC treatment. Compared to 3DRVEF, speckle tracking echocardiography is more useful in revealing deterioration of RV systolic function after radiotherapy.
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Introduction: Pembrolizumab combined with chemotherapy has become the standard of care for patients with non-small-cell lung cancer (NSCLC) and the expression of programmed death ligand 1 (PD-L1) in <50% of tumour cells (TC). Methods: We evaluated the efficacy of the treatment in real-world practice, paying attention to the predictive factors, with a special focus on low level of PD-L1 expression. This study is a multicenter retrospective analysis of patients with stage IV NSCLC. Results: A group of 339 consecutive patients was analysed, among them 51% patients with low PD-L1 expression. In the overall population, the ORR was 40.6%, median PFS and OS were 13 months (95% CI 11.4-15) and 16.8 months (95% CI 13.3-20.3), respectively. In multivariate analysis for the entire study population, performance status - ECOG 1 vs. 0 (HR 2.2, 95%CI 1.1-4.6; p=0.02), neutrophil to lymphocyte ratio (NLR)>3 (HR 2.3, 95%CI 1.3-4.2; p=0.04), presence of liver (HR 2.0, 95%CI 1-3.7; p=0. 03) and bone metastases (HR 1.3, 95%CI 1-3; p=0.04), weight loss (HR 1.8, 95%CI 1.1-2.8; p=0.01) and sum of measurable lesions diameters >110 mm (HR 1.7, 95%CI 1-2.9, p=0.049) had a negative impact on OS. Conclusions: In the real world, patients can clinically benefit from immunochemotherapy, regardless of the expression of PD-L1 and the histological type. Other clinicopathological factors such as performance status, extent, and location of secondary lesions have prognostic significance.
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Non-small-cell lung cancer (NSCLC) represents 85% of new cases of lung cancer. Over the past two decades, treatment of patients with NSCLC has evolved from the empiric use of chemotherapy to more advanced targeted therapy dedicated to patients with an epidermal growth factor receptor (EGFR) mutation. The multinational REFLECT study analyzed treatment patterns, outcomes, and testing practices among patients with EGFR-mutated advanced NSCLC receiving first-line EGFR tyrosine kinase inhibitor (TKI) therapy across Europe and Israel. The aim of this study is to describe the Polish population of patients from the REFLECT study, focusing on treatment patterns and T790M mutation testing practice. A descriptive, retrospective, non-interventional, medical record-based analysis was performed on the Polish population of patients with locally advanced or metastatic NSCLC with EGFR mutations from the REFLECT study (NCT04031898). A medical chart review with data collection was conducted from May to December 2019.The study involved 110 patients. Afatinib was used as the first-line EGFR-TKI therapy in 45 (40.9%) patients, erlotinib in 41 (37.3%), and gefitinib in 24 (21.8%) patients. The first-line EGFR-TKI therapy was discontinued in 90 (81.8%) patients. The median progression-free survival (PFS) on first-line EGFR-TKI therapy was 12.9 months (95% CI 10.3-15.4). A total of 54 patients started second-line therapy, of whom osimertinib was administered to 31 (57.4%). Among 85 patients progressing on first-line EGFR-TKI therapy, 58 (68.2%) were tested for the T790M mutation. Positive results for the T790M mutation were obtained from 31 (53.4%) tested patients, all of whom received osimertinib in the next lines of therapy. The median overall survival (OS) from the start of first-line EGFR-TKI therapy was 26.2 months (95% CI 18.0-29.7). Among patients with brain metastases, the median OS from the first diagnosis of brain metastases was 15.5 months (95% CI 9.9-18.0). The results of the Polish population from the REFLECT study highlight the need for effective treatment of patients with advanced EGFR-mutated NSCLC. Nearly one-third of patients with disease progression after first-line EGFR-TKI therapy were not tested for the T790M mutation and did not have the opportunity to receive effective treatment. The presence of brain metastases was a negative prognostic factor.
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Ultrasonic vocalization (USV) is one of the measurable behavioral parameters of sociosexual interactions in rats. To precisely and accurately describe the neurobehavioral properties of USV and the potentially related specific emotional responsiveness of animals, we need to know which animals vocalize and what is their exact behavioral and physiological response. To this end, we modified the non-contact cage [non-contact erection model (NCE)] by adding a modification [vocalization-non-contact erection (VOC-NCE)] that makes it possible to assign emitted ultrasonic signals to a particular animal. Typically, the NCE cage consists of two compartments separated by perforated baffles. A male is placed in one section, and a receptive female is placed in the other section. This makes possible the accurate description of sexual parameters related to the cues controlled by the experimenter. In VOC-NCE, we completely separated the male USV from the female USV by three appropriately perforated baffles and located microphones combined with ultrasonic screening. We recorded emission in both typical bands, the so-called 22- and 50-kHz bands, with various subtypes, thus highlighting the utility of our protocol to investigate the sexual dimorphism of vocalization. Similar to the anticipatory model, we showed that emission can occur without acoustic feedback from concomitants during the VOC-NCE test. Therefore, we propose a relatively simple method for assigning individual vocalization. We discuss its usefulness and limitations in assessing vocal differentiation related to sexual parameters, adaptive changes during conditioning procedures, and further applications.
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PURPOSE: To establish a transborder virtual tumor board (VTB) fostering state-of-the-art management of cancer patients by exchanging knowledge and expertise among oncologists in Central and Southeastern Europe (CEE). METHODS: We established and implemented a VTB based on the WebEx platform. This allowed for password-protected and secure upload of patient cases to be presented and discussed among colleagues from various oncology centers scattered throughout CEE in order to arrive at a recommendation for further diagnoses and/or treatment. RESULTS: A total of 73 cases from 16 oncology centers located in 11 CEE countries were uploaded by 22 physicians; 71 were discussed over the course of 17 virtual meetings between June 2018 and May 2019 and 12 different kinds of malignant diseases were discussed with lung cancer (46.6%), melanoma (19.2%) and bladder cancer (13.6%) being the most commonly presented tumor entities. Of the discussed patients, 93.3% had stage IV disease at the time of presentation, 62.6% received chemotherapy or targeted treatment and 67.1% were treated with immune checkpoint inhibitors (ICPIs). The most common causes for presentation and discussion of patient cases were related to the use of ICPIs (80%). CONCLUSION: When the need for expertise exceeds locally available resources, web-based VTBs provide a feasible way to discuss patient cases and arrive at conclusions regarding diagnoses and/or treatment across large geographic distances. Moreover, VTBs provide an innovative way for proper, state-of-the-art management of patients with malignant diseases in times of social distancing and the resulting need for restricted interaction during the current SARS-CoV2 (severe acute respiratory syndrome coronavirus type 2) pandemic.
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COVID-19 , Neoplasias Pulmonares , Humanos , Inibidores de Checkpoint Imunológico , SARS-CoV-2 , COVID-19/epidemiologia , Europa (Continente)RESUMO
Radiation treatment of early stage nonsmall cell lung cancer has evolved over the past 2 decades to progressively more hypofractionated treatment courses. Results comparable to surgical resection are seen with stereotactic body radiotherapy, which is now the standard of care for medically inoperable patients, and a treatment option for operable patients as well. Understanding of the optimal radiation dose and fractionation are evolving, especially for central tumors which have higher treatment toxicity than peripheral tumors.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Estadiamento de Neoplasias , Hipofracionamento da Dose de Radiação , Radiocirurgia/métodosRESUMO
The combination of radiotherapy (RT) with targeted agents in non-small cell lung cancer (NSCLC) has been expected to improve the therapeutic ratio and tumor control. The EGFR blockade enhances the antitumor effect of RT. The ALK inhibition elicits anti-proliferative, pro-apoptotic and antiangiogenic effects in ALK-positive NSCLC cell lines, enhanced by the exposure to RT. The antiangiogenic agents normalize pathological tumor vessels, thus decrease tumor cell hypoxia and improve radiosensitivity. To date, however, none of the targeted agents combined with RT has shown proven clinical benefit over standard chemoradiation (CRT) in locally advanced NSCLC. The risk of potential excessive toxicity related to the therapeutic combination of RT and targeted agents cannot be ignored. Well-designed clinical trials may allow development of more effective combination strategies. Another potential application of combined RT and targeted therapies in oncogene-driven NSCLC is metastatic oligoprogressive or oligopersistent disease. The use of RT in oligoprogressive oncogene-driven NSCLC, while continuing first line targeted therapy, can potentially eradicate resistant cell clones and provide survival benefit. Likewise, the consolidation of oligopersistent foci (molecularly resistant to first line targeted therapy) may potentially interfere with the natural course of the disease by avoiding or delaying progression. We discuss here the molecular and radiobiological mechanisms of combining RT and targeted agents, and summarize current clinical experience.
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The role of Wnt family proteins, E-cadherin, and ß-catenin in non-small cell lung cancer (NSCLC) is unclear. In this study, we assessed the expression of these proteins as well as their reciprocal interaction and clinical relevance in NSCLC. Immunohistochemical expression of Wnt1, Wnt2, E-cadherin, and ß-catenin was assessed in 208 patients with NSCLC who underwent curative pulmonary resection. Expression of Wnt1, Wnt2, and E-cadherin was found in 49.5%, 22.3%, and 37.4% of the patients, respectively, whereas expression of membranous and cytoplasmic ß-catenin was found in 23.7% and 34.8% of the patients, respectively. The expression of Wnt1 and E-cadherin was lower in squamous cell carcinoma than in adenocarcinoma and large cell carcinoma, and the expression of both Wnt proteins, E-cadherin, and membranous ß-catenin was lower in poorly differentiated compared with well-differentiated tumors. None of the analyzed proteins was associated with relapse-free or overall survival. Expression of Wnt1, Wnt2, E-cadherin, and ß-catenin is a common occurrence in NSCLC and is related to tumor histology and grade. However, these proteins have no prognostic role in operable NSCLC.
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Antígenos CD/genética , Caderinas/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Proteína Wnt1/genética , Proteína Wnt2/genética , beta Catenina/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/genética , Feminino , Humanos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
Tubal factor infertility occurs in 30-35% of infertile pairs and may be caused by impaired muscular contractility and ciliary beating as well as immunological imbalance and chronic inflammation. Newly discovered telocytes (TCs) have a wide palette of features, which play a role in oviduct physiology. We have observed tissue samples from human fallopian tubes in patients with and without uterine myoma by immunolabelling. According to the immunohistochemical co-expression of markers, it has been determined that TCs are engaged in a wide range of physiological processes, including local innervation, sensitivity to hypoxia, regulation of calcium, and sex steroid hormones balances. Due to the proximity of NOS- and ChAT-positive nerve fibers and the expression of ion channels markers, tubal TCs might be considered conductor cells. Additionally, their integration in contractions and cilia physiology in the context of fertility has been revealed. We have observed the difference in telocytes expression in the human oviduct between groups of patients and attempted to describe this population of cells specifically in the case of infertility development, a clinically relevant avenue for further studies.
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This paper presents the new TNM classification in lung cancer and its history. Seventh edition of tumor, node, metastasis (TNM) classification in lung cancer has been published by the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC) at the beginning of 2009. The changes were based upon the results of the international project of the International Association for the Study of Lung Cancer (IASLC). The database included 81.495 patients from the entire world (68.463 with non-small cell lung cancer and 13.032 with small cell lung cancer) treated with various modalities between 1990 and 2000. The collected data were validated internally and externally. The tumor size was considered of prognostic relevance: T1 tumors were subdivided into T1a (≤ 2 cm) and T1b (ã 2 cm - ≤ 3 cm), T2 tumors into T2a (ã 3 cm - ≤ 5 cm) and T2b (ã 5 cm - ≤ 7 cm), and T2 tumors ã 7 cm were reclassified as T3. Tumors with the additional nodules in the same lobe as the primary tumor were classified as T3, those with additional nodules in another ipsilateral lobe - as T4. There were no changes in N category. In the M category, M1 was subclassified into M1a (contralateral lung nodules and pleural dissemination) and M1b (distant metastasis). Large T2 tumors (T2bN0M0) were upstaged from IB to IIA, small T2 tumors (T2aN1M0) were downstaged from the IIB to IIA and T4N0-N1M0 - from IIIB to IIIA. The TNM classification was also recommended for small cell lung cancer instead of previously used categories of limited and extensive disease.