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1.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 38(5): 502-508, 2020 Oct 01.
Artigo em Chinês | MEDLINE | ID: mdl-33085232

RESUMO

OBJECTIVE: To investigate whether hyperthermia, chemotherapy and thermo-chemotherapy could trigger the expression of damage-associated molecular patterns (DAMPs). METHODS: The optimal working concentration of pingyangmycin (PYM) was detected by CCK-8 assay, and temperatures of 39, 42, and 45 ℃ were applied to the oral squamous cell carcinoma CAL27, SCC-15, and Tca8113 cell lines. The effects of different treatments on the apoptosis, calreticulin (CRT) membrane expression and high-mobility group box 1 (HMGB1) secretion of the cells were detected by using Annexin V/propidium iodide (PI), flow cytometry and enzyme-linked immunosorbent assay (ELISA) assay. SPSS 20.0 software was used for statistical analysis. RESULTS: Both hyperthermia and chemotherapy could increase the membrane expression of CRT and the secretion of HMGB1, and furthermore, thermo-chemotherapy group showed significantly increased in apoptosis, CRT membrane expression rate and HMGB1 secretion compared with chemotherapy group, and the difference was statistically significant (P<0.05). CONCLUSIONS: Hyperthermia, chemotherapy and thermo-chemotherapy could induce oral squamous cell carcinoma cells succumb to death, and at the same time, they can effectively induce the membrane expression of CRT, and promote the secretion of HMGB1. Moreover, thermo-chemotherapy is significantly better than that of chemotherapy alone in the induction of cell apoptosis and DAMPs expression.


Assuntos
Carcinoma de Células Escamosas , Proteína HMGB1 , Neoplasias Bucais , Apoptose , Carcinoma de Células Escamosas/terapia , Linhagem Celular Tumoral , Humanos , Neoplasias Bucais/terapia
2.
Oncology (Williston Park) ; 34(9): 370-376, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32965669

RESUMO

In an asymptomatic 77-yearold woman, former 55 packyears smoker, a routine X-ray showed a 45-mm superior left lobe lesion. A chest CT scan confirmed a 36-mm superior left lobe lesion and an aortic-pulmonary lymph node enlargement measuring 42 mm, suspicious for neoplasia. A PET-CT scan showed an elevated uptake in the primary lesion, in the aortic-pulmonary lymph node, and in the left hilar lymph node with a standardized uptake value - 40 and 4.3, respectively. CT-guided lung biopsy showed a lung squamous cell carcinoma. An endobronchial ultrasound-guided transbronchial needle aspiration for lymph-node staging was negative for lymph node spread. Brain MRI was negative. Final staging was determined to be a IIIA (T2bN2) squamous cell carcinoma of the lung.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Escamosas/terapia , Infecções por Coronavirus/diagnóstico , Neoplasias Pulmonares/terapia , Pneumonia Viral/diagnóstico , Pneumonia/diagnóstico , Idoso , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Betacoronavirus , Carboplatina/administração & dosagem , Carcinoma de Células Escamosas/diagnóstico por imagem , Quimiorradioterapia , Quimioterapia de Consolidação , Diagnóstico Diferencial , Feminino , Humanos , Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Paclitaxel/administração & dosagem , Pandemias , Pneumonia/induzido quimicamente
3.
Medicine (Baltimore) ; 99(32): e21521, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769890

RESUMO

RATIONALE: The establishment of lung isolation is often particularly challenging for the anesthesiologist in patients with difficult airway. Usually, orotracheal intubation with double lumen tube is the commonly used technique for achieving 1 lung anesthesia. Whereas, in patients with limited mouth opening and restricted cervical mobility, this technique becomes extremely difficult and hazardous. We report a case in which bronchial blocker placement was succeeded via both nostrils in a difficult airway due to restricted mouth opening. PATIENT CONCERNS: A 50-year-old, non-smoking female with a painless mass in the left upper lobe. She had a 10-year history of ankylosing spondylitis and squamous cell carcinoma of the floor of the mouth after 5 operations 4 years previously. DIAGNOSES: Left upper lobe adenocarcinoma, ankylosing spondylitis and oral squamous cell carcinoma. INTERVENTIONS: To achieve 1 lung anesthesia, both nostrils were used for extraluminal bronchial blocker placement. OUTCOMES: Initially, oral intubation was selected for establishing a patent airway but failed. Then switched to nasal canal for insertion, after several attempts, a conventional nasal intubation tube (internal diameter 6.0 mm) was placed via 1 nostril under topical anesthesia, with the aid of a flexible fiberoptic bronchoscope, and a bronchial blocker was advanced to the desired position via the other nostril. LESSONS: In difficult airway with limited mouth opening and restricted cervical mobility, multidisciplinary experts participated discussion is a prerequisite for contemplating a scientific plan. Preoperative computed tomography scan and 3-dimensional computed tomography reconstruction would be helpful in detecting the narrowest part of airway conduit and determining a safe, reliable, and feasible airway program.


Assuntos
Adenocarcinoma de Pulmão/terapia , Obstrução das Vias Respiratórias/terapia , Intubação/métodos , Neoplasias Pulmonares/terapia , Nariz , Ventilação Monopulmonar/métodos , Adenocarcinoma de Pulmão/complicações , Obstrução das Vias Respiratórias/complicações , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/terapia , Feminino , Humanos , Neoplasias Pulmonares/complicações , Pessoa de Meia-Idade , Boca/patologia , Neoplasias Bucais/complicações , Neoplasias Bucais/terapia , Espondilite Anquilosante/complicações , Espondilite Anquilosante/terapia
4.
PLoS One ; 15(8): e0237114, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32760099

RESUMO

BACKGROUND: This study aimed to investigate the correlation between primary tumor volume and cancer failure patterns in esophageal squamous cell carcinoma (ESCC) treated with definitive concurrent chemoradiotherapy (CCRT) and examine whether increasing radiation dose can improve the outcome. METHODS: We retrospectively reviewed 124 patients with stage III ESCC treated by definitive CCRT. The primary tumor volume calculated from the radiotherapy planning computed tomography scans was correlated to treatment response, time to disease progression, and overall survival. We further analyzed whether a higher radiation dose correlated with better disease control and patient survival. RESULTS: Patients with poor CCRT response had a larger primary tumor volume than those with good response (97.9 vs 64.3 cm3, P = 0.032). The optimal cutoff value to predict CCRT response was 55.3 cm3. Large primary tumor volume (≥ 55.3 cm3) correlated with shorter time to tumor progression in the esophagus (13.6 vs 48.6 months, P = 0.033) compared with small tumor volume (< 55.3 cm3). For the large esophageal tumors (≥ 55.3 cm3), radiation dose > 60 gray significantly prolonged the time to tumor progression in esophagus (20.3 vs 10.1 months, P = 0.036) and overall survival (12.2 vs 8.0 months, P = 0.030), compared with dose ≤ 60 gray. In contrast, higher radiation dose did not benefit local disease control or overall survival in the small esophageal tumors (< 55.3 cm3). CONCLUSION: Large primary tumor volume correlates with poor local control and overall survival in ESCC treated with definitive CCRT. Radiation dose > 60 gray can improve the outcomes in patients with large primary tumor. Further prospective dose escalation trials are warranted.


Assuntos
Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/métodos , Neoplasias Esofágicas/terapia , Doses de Radiação , Idoso , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Carga Tumoral
5.
J Cancer Res Ther ; 16(3): 478-484, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719254

RESUMO

Context: As the number of head-and-neck cancer (HNC) patients are high in our subcontinent, the study was designed to reduce the treatment time and increase efficacy. Aims: Comparative evaluation of the efficacy, toxicity, local control, and survival of concomitant boost radiotherapy (CBRT), CBRT with concurrent chemoradiation (CBRT + CCT) and conventionally fractionated radiotherapy with concomitant chemotherapy (CFRT + CCT) in locally advanced HNC (LAHNC). Materials and Methods: Patients with LAHNC were randomly assigned to 3-groups of 30-patients each. Group I (CBRT) received, 45 Gy/25#/5-weeks and 18 Gy/10# concomitant boost in the last 2-week of treatment, receiving a total dose of 63 Gy. Group II (CBRT + CCT) received CBRT with concomitant cisplatin 75 mg/m 2 on day 1, 17, and 34. Group III (CFRT + CCT) received 64 Gy/32#/6.2 weeks, concurrent with injection cisplatin 75 mg/m 2 on day 1, 22, and 42. Statistical Analysis Used: Stata 9.0 SPSS and Chi-square test were used for analysis and disease-free survival (DFS) rates were calculated using the Kaplan-Meier method. Results: The median follow-up period was 8.2 months. At last follow-up, locoregional control was 36%, 57%, and 40% and DFS was seen in 33%, 53%, and 40% of patients in Group I, II, and III, respectively. Grade-3 cutaneous reactions were significantly higher in Group-II as compared to that of Group-III (P = 0.033) and Group-I (P = 0.715). Conclusion: All three groups have similar response rates and DFS with manageable toxicity.


Assuntos
Carcinoma de Células Escamosas/mortalidade , Quimiorradioterapia/mortalidade , Cisplatino/uso terapêutico , Neoplasias de Cabeça e Pescoço/mortalidade , Adulto , Idoso , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Terapia Combinada , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Segurança do Paciente , Estudos Prospectivos , Taxa de Sobrevida , Resultado do Tratamento
6.
S Afr Med J ; 110(3): 243-248, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32657703

RESUMO

BACKGROUND: Anal carcinoma is rare. Clinicopathological features influencing outcome have not been determined in HIV-negative and HIV-positive patients in South Africa. OBJECTIVES: To compare presentation and treatment tolerance among HIV-positive and negative patients. METHODS: This study was a retrospective analysis of prospectively collected data on patients with squamous cell carcinoma of the anus. Patients with known HIV status were extracted from the anal cancer database and analysed. Data analysed included demographics, clinical features, stage, pathology and treatment outcome. RESULTS: There were 268 patients with anal squamous cell carcinoma (n=135 HIV-positive and n=33 negative). The median age was 39 years and 53 years for HIV-positive and negative patients, respectively, the male/female ratio was 1:2.7 and 1:1.8 for the two groups, and the ratio of anal margin to canal distribution was 1.3:1 and 1:1. Disease stage was similar, with minor differences. The resection rate was 17% in HIV-positive patients and 9% in those who were HIV-negative. Half the patients in both groups were eligible for definitive therapy, and side-effects of oncotherapy occurred with similar frequency in both groups. The recurrence rate was 7% in both groups and the disease-free interval was similar. Overall survival was longer for HIV-negative patients (p=0.0240). CONCLUSIONS: The prevalence of anal squamous cell carcinoma is much higher in individuals with HIV infection than in those who are HIV-negative. HIV-positive patients present at a younger age and with locally advanced disease that responds less well to standard treatment, and their survival is poorer.


Assuntos
Neoplasias do Ânus/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Infecções por HIV/complicações , Adulto , Neoplasias do Ânus/mortalidade , Neoplasias do Ânus/terapia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento
7.
Praxis (Bern 1994) ; 109(9): 697-703, 2020 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-32635845

RESUMO

Update for Diagnosis and Management of HPV-Driven Oropharyngeal Cancer Abstract. In the past decades, an increasing incidence of oropharyngeal squamous cell cancer could be observed. More than twenty years ago, a correlation between a pharyngeal Human papillomavirus high-risk type infection and the development of oropharyngeal cancer has been suspected. Especially younger patients without the former risk factors smoking and alcohol have a higher prevalence for this cancer type. HPV-associated cancer is developing in the lymphatic tissue of the tonsils and the base of the tongue. HPV-driven tumors can be defined as a clinical and morphologic distinct tumor entity with a significantly better prognosis compared to tumors based on smoking and alcohol consumption. They are demonstrating a clearly better treatment response irrespective of the treatment modality. The tumor development is assumed to be comparable to cervical cancer, probably through a step-wise process from dysplasia to invasive cancer. In the pharynx, no HPV-associated precursor lesions have been detected so far. Therefore, Screening program proven to be very successful in the cervix have not could not have been implemented so far. The reduction of HPV-associated tumor burden in the cervix is likely to be compensated by the rising number of HPV-driven oropharyngeal cancer. P16 as a surrogate marker for HPV has been implemented in the 8th edition of the TNM classification for oropharyngeal cancer. A worldwide accepted definition of an HPV-driven tumor is lacking so far. P16 immunhistochemistry or HPV-DNA detection by PCR as single markers have an insufficient sensitivity and specificity. A combination of both markers demonstrates a higher accuracy compared to the gold standard RNA. Antibodies to HPV oncoproteins are reliable diagnostic and prognostic markers that could in the future possibly serve for early tumor detection.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Biomarcadores Tumorais , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/virologia , Inibidor p16 de Quinase Dependente de Ciclina , Feminino , Humanos , Neoplasias Orofaríngeas/terapia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/terapia , Prognóstico
8.
Am Surg ; 86(6): 703-714, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32683973

RESUMO

There is a controversy regarding the optimal time to assess anal squamous cell carcinoma (SCC) response to chemoradiation and when salvage abdominoperineal resection (APR) should be offered. A retrospective cohort study was performed on patients with stage I-III anal SCC treated with chemoradiation in the National Cancer Database (2004-2015). The time between radiation and APR was recorded. Logistic regression and Cox proportional hazard analysis were used to determine predictors of resection margin status and overall survival. The cohort included 23 050 patients, of whom 545 (2.4%) underwent salvage APR. The median (IQR) time between radiation and resection was 3.8 (2.4-5.5) months. The rate of positive margins was 19.0%. Positive margins were more common in male, non-white patients with larger tumors, pathologic upstaging of T stage, and ≥3 months between chemoradiation and resection (all P < .05). Observing for ≥3 months between chemoradiation and APR remained associated with positive margins, even after adjusting for pretreatment tumor size (odds ratio = 2.56, 95% CI 1.46-4.47). Our data, based on the largest published cohort of anal SCC patients treated with chemoradiation and subsequent APR, suggest that patients at high risk of local treatment failure, particularly non-white men with large tumors, may benefit from early interim restaging and earlier consideration of salvage surgery.


Assuntos
Neoplasias do Ânus , Carcinoma de Células Escamosas , Quimiorradioterapia/métodos , Terapia de Salvação/métodos , Adulto , Idoso , Neoplasias do Ânus/patologia , Neoplasias do Ânus/terapia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Terapia Combinada , Feminino , Humanos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo
9.
Nat Cell Biol ; 22(7): 758-766, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32483388

RESUMO

Cancer-associated fibroblasts (CAFs) perform diverse roles and can modulate therapy responses1. The inflammatory environment within tumours also influences responses to many therapies, including the efficacy of oncolytic viruses2; however, the role of CAFs in this context remains unclear. Furthermore, little is known about the cell signalling triggered by heterotypic cancer cell-fibroblast contacts and about what activates fibroblasts to express inflammatory mediators1,3. Here, we show that direct contact between cancer cells and CAFs triggers the expression of a wide range of inflammatory modulators by fibroblasts. This is initiated following transcytosis of cytoplasm from cancer cells into fibroblasts, leading to the activation of STING and IRF3-mediated expression of interferon-ß1 and other cytokines. Interferon-ß1 then drives interferon-stimulated transcriptional programs in both cancer cells and stromal fibroblasts and ultimately undermines the efficacy of oncolytic viruses, both in vitro and in vivo. Further, targeting IRF3 solely in stromal fibroblasts restores oncolytic herpes simplex virus function.


Assuntos
Fibroblastos Associados a Câncer/imunologia , Instabilidade Genômica , Fator Regulador 3 de Interferon/metabolismo , Proteínas de Membrana/metabolismo , Terapia Viral Oncolítica , Neoplasias Cutâneas/imunologia , Células Estromais/imunologia , Adulto , Animais , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Células Cultivadas , Citocinas , Interações Hospedeiro-Patógeno , Humanos , Fator Regulador 3 de Interferon/genética , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Vírus Oncolíticos/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Células Estromais/metabolismo , Células Estromais/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Oncol Res Treat ; 43(7-8): 372-379, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32485721

RESUMO

INTRODUCTION: Esophageal cancer (EC) is a common malignant tumor entity with increasing occurrence. The incidence of esophageal adenocarcinoma (AC), particularly, is constantly rising in the Western world. The mainstays of therapy with curative intent for EC in advanced stages are neoadjuvant radiochemotherapy (neoRCT) with surgery and definitive radiochemotherapy (defRCT). METHODS: We examined our internal files to identify patients suffering from EC. Palliative cases were excluded. Statistical testing was performed by χ2 test, Student's t test, Kaplan-Meier analyses, and the Mann-Whitney U test. RESULTS: One hundred and twenty-two cases were included. Histology revealed squamous cell carcinoma in 92 cases and AC in 23 cases. Ninety-five patients underwent defRCT, 27 underwent neoRCT, and 114 (in both therapy regimes) received simultaneous chemotherapy. There was no difference in the overall survival (OS) (p = 0.654; HR 1.145; 95% CI 0.629-2.086) or and progression-free survival (PFS) (p = 0.912) of patients who underwent neoRCT or defRCT. Median OS was 13.5 (2-197) months for defRCT patients and 19.5 (2-134) months for neoRCT patients (p = 0.751). Karnofsky index (KI) with a cut-off of 70% was strongest, but not a significant parameter for OS (p = 0.608) or PFS (p = 0.137). CONCLUSION: defRCT is a valid and an equal alternative to neoRCT for patients suffering from EC. Selection of patients for therapy is of crucial relevance. Further studies and improvements in follow-up are needed when neoRCT has been completed before surgery, in order to spare the patient undergoing operative treatment if there is complete remission. The identification of valid markers urgently needed to limit treatment side effects.


Assuntos
Adenocarcinoma/terapia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia Adjuvante/mortalidade , Neoplasias Esofágicas/terapia , Terapia Neoadjuvante/mortalidade , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Intervalo Livre de Doença , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
12.
J Cancer Res Ther ; 16(1): 116-119, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32362620

RESUMO

Introduction: The benefit of definitive chemoradiotherapy (CRT) in elderly patients with locally advanced esophageal cancer is not well established. We perform a single institutional retrospective study of CRT in terms of toxicity in elderly patients (age more than 60 years) as compared with young cohort (age <60 years) in locally advanced nonmetastatic esophageal cancer. Patients and Methods: A total 145 of patients, 79 in young age (Group A) and 66 patients of elder age (Group B) with Stage II and III squamous cell carcinoma of the esophagus with ECOG PS of 0-1, who had undergone definitive CRT at our institute from January 2015 to November 2018 were selected for this analysis. Chemotherapy was cisplatin (40 mg/m2) given concurrently on weekly basis with radiotherapy (RT). Total prescribed dose of RT was 50.4 Gy at the rate of 1.8 Gy per fraction. Median age was 40 years (25-60 years) and 65 years (60-75 years) in young and elderly group, respectively. Follow-up is done at median of 28 months (1-48 months) after treatment. Results: Acute Grade 2-3 esophagitis was seen in 48.10% in young cohort, while it was 60.6% in older group. Grade 2-3 nausea and vomiting was seen in 32.91% in young age patients, while it was 45.5% in elder patients. No statistically significant difference is seen in acute treatment-related toxicity in young and elderly group. Conclusion: Our conclusion is that patients with adequate functional status should not be excluded from curative CRT based on age alone.


Assuntos
Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/efeitos adversos , Cisplatino/efeitos adversos , Neoplasias Esofágicas/terapia , Esofagite/etiologia , Náusea/etiologia , Adulto , Fatores Etários , Idoso , Antineoplásicos/efeitos adversos , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia/métodos , Estudos de Coortes , Neoplasias Esofágicas/patologia , Esofagite/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento
13.
Hum Cell ; 33(3): 641-651, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32419118

RESUMO

MiR-27b-3p has been reported to function as tumor suppressor in several tumors, including breast cancer and lung cancer. Recently, miR-27b-3p has been identified to be significantly down-regulated in esophageal cancer. However, the clinical significance and biological role of miR-27b-3p in esophageal squamous cell carcinoma (ESCC) still remain unclear. In this study, the expression levels of miR-27b-3p were significantly reduced in ESCC clinical tissues and ESCC cell lines (EC97069 and TE-1). Moreover, down-regulated expression of miR-27b-3p was associated with poor cell differentiation, TNM stage and lymph node metastasis. Specially, overexpression of miR-27b-3p significantly suppressed cell proliferation, migration and invasion in vitro using CCK-8 and transwell assays. Targetscan bioinformatics predictions and luciferase reporter assay confirmed that nuclear factor erythroid 2-related factor 2 (NFE2L2, Nrf2) was a direct target gene of miR-27b-3p. Nrf2 expression was significantly increased in ESCC tissues compared with adjacent tissues. Up-regulated expression of Nrf2 was correlated with TNM stage and lymph node metastasis. Functionally, knockdown of Nrf2 exhibited similar effects to overexpression of miR-27b-3p. Higher expression of ZO-1, E-cadherin and lower expression of N-cadherin, Vimentin and Claudin-1 were observed after miR-27b-3p overexpression of Nrf2 knockdown. Rescue experiments proved that miR-27b-3p suppressed cell proliferation, migration, invasion and epithelial to mesenchymal transition (EMT) via suppression of Nrf2. Taken together, the newly identified miR-27b-3p/Nrf2 axis might represent a new candidate therapeutic target for ESCC treatment.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Genes Supressores de Tumor , MicroRNAs/genética , MicroRNAs/fisiologia , Fator 2 Relacionado a NF-E2/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Humanos , Terapia de Alvo Molecular , Invasividade Neoplásica/genética
14.
Nat Commun ; 11(1): 2124, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32358507

RESUMO

Penile squamous cell carcinoma (PSCC) accounts for over 95% of penile malignancies and causes significant mortality and morbidity in developing countries. Molecular mechanisms and therapies of PSCC are understudied, owing to scarcity of laboratory models. Herein, we describe a genetically engineered mouse model of PSCC, by co-deletion of Smad4 and Apc in the androgen-responsive epithelium of the penis. Mouse PSCC fosters an immunosuppressive microenvironment with myeloid-derived suppressor cells (MDSCs) as a dominant population. Preclinical trials in the model demonstrate synergistic efficacy of immune checkpoint blockade with the MDSC-diminishing drugs cabozantinib or celecoxib. A critical clinical problem of PSCC is chemoresistance to cisplatin, which is induced by Pten deficiency on the backdrop of Smad4/Apc co-deletion. Drug screen studies informed by targeted proteomics identify a few potential therapeutic strategies for PSCC. Our studies have established what we believe to be essential resources for studying PSCC biology and developing therapeutic strategies.


Assuntos
Carcinoma de Células Escamosas/terapia , Imunoterapia/métodos , Neoplasias Penianas/terapia , Animais , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular , Cisplatino/farmacologia , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células Mieloides/efeitos dos fármacos , Células Mieloides/metabolismo , Células Supressoras Mieloides/citologia , Células Supressoras Mieloides/metabolismo , Neoplasias Penianas/metabolismo , Proteômica , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Análise Serial de Tecidos , Transcriptoma/genética
15.
JAMA Netw Open ; 3(5): e204307, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32379332

RESUMO

Importance: The role of surgery in early-stage cervical cancer has been established, but it is controversial in locally advanced cervical cancer. Objective: To determine whether a radical hysterectomy method with extended removal of paracervical tissue for locally advanced cervical cancer is associated with satisfactory oncological outcomes. Design, Setting, and Participants: This retrospective cohort study was conducted from January 1, 2002, to December 31, 2011, and participants were patients with cervical cancer at a single tertiary center in Northern Japan. The median follow-up period was 106 months, and none of the patients were lost to follow-up at less than 60 months. Data analyses were performed from July 1, 2017, to December 31, 2018. Exposures: Patients underwent radical hysterectomy using the Okabayashi-Kobayashi method. Bilateral nerve preservation was used for stage IB1/IB2 disease and unilateral nerve preservation for stage IIA/IIB if disease extension outside the uterine cervix was 1-sided. Chemotherapy was used as the choice of adjuvant treatment for patients with an intermediate or high risk of recurrence, while some patients chose or were assigned to radiotherapy. Main Outcomes and Measures: Primary outcomes were the 5-year local control rate and 5-year overall survival rate along with risk factor analysis. Results: Of 121 consecutive patients, 76 (62.8%) had early-stage cervical cancer in 2008 International Federation of Gynecology and Obstetrics stages IB1 and IIA1 and 45 (37.2%) had locally advanced cervical cancer in stages IB2, IIA2, and IIB. The median (range) age was 42 (26-68) years. Adjuvant radiotherapy was used in 2 patients (3%) with early-stage cervical cancer and 3 (7%) of those with locally advanced cervical cancer. The 5-year local control rates for early-stage cervical cancer and locally advanced cervical cancer were 99% and 87%, respectively. The 5-year overall survival rates for early-stage cervical cancer and locally advanced cervical cancer were 95% and 82%, respectively. Cox regression analysis showed that lymph node metastasis and histology of adeno(squamous)carcinoma were independent risk factors for the overall survival of patients with cervical cancer treated with radical hysterectomy. Conclusions and Relevance: The nerve-sparing Okabayashi-Kobayashi radical hysterectomy for locally advanced cervical cancer may provide survival not inferior to radical hysterectomy or radiotherapy in published literature. The applicability of radical hysterectomy with adjuvant chemotherapy for locally advanced cervical cancer needs to be validated by prospective comparative trials.


Assuntos
Recidiva Local de Neoplasia/mortalidade , Neoplasias do Colo do Útero/mortalidade , Adenocarcinoma/mortalidade , Adenocarcinoma/terapia , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , Quimioterapia Adjuvante , Estudos de Coortes , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Histerectomia , Japão , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/terapia , Radioterapia Adjuvante , Estudos Retrospectivos , Fatores de Risco , Neoplasias do Colo do Útero/terapia
16.
Cutis ; 105(3): 138-142;E5, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32352432

RESUMO

Nonmelanoma skin cancer (NMSC) is the most common malignancy worldwide, and the incidence continues to increase. Originally, treatment options for NMSCs largely relied on destructive and surgical methods. Basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) commonly are treated with cryosurgery, electrodesiccation and curettage, or more definitive surgical options. Over time, topical agents such as 5-fluorouracil, imiquimod, ingenol mebutate, and various forms of aminolevulinic acid (ALA) for photodynamic therapy (PDT) were included for superficial lesions as well as field treatment. The development of oral hedgehog (Hh) inhibitors such as vismodegib offered a promising alternative to patients with advanced disease. Each treatment has its own specific indications and side effects, thus there is always room for novel therapeutic approaches. We review new and potential treatments for NMSCs since 2018 including topical sonidegib, cemiplimab, taladegib, posaconazole, radiation therapy (RT), combination RT with vismodegib, PDT, and laser therapies.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Basocelular/terapia , Carcinoma de Células Escamosas/terapia , Neoplasias Cutâneas/terapia , Carcinoma Basocelular/metabolismo , Carcinoma de Células Escamosas/metabolismo , Humanos , Terapia a Laser , Fotoquimioterapia , Radioterapia , Neoplasias Cutâneas/metabolismo
18.
J Laryngol Otol ; 134(4): 369-371, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234087

RESUMO

OBJECTIVE: This paper presents a case of an isolated pituitary fossa metastasis on a background of a previously treated tonsillar squamous cell carcinoma. CASE REPORT: A 64-year-old male, diagnosed with a primary p16-negative squamous cell carcinoma in the right tonsil, was treated with a course of chemoradiotherapy with curative intent. Positron emission tomography/computed tomography, performed at six months post-treatment, revealed a good local response and no distant metastases. The patient was placed on routine follow up at two-monthly intervals. Two months into follow up, he presented with a right-sided oculomotor nerve palsy and partial Horner's syndrome. Imaging and biopsy revealed a pituitary fossa metastasis (p16-negative squamous cell carcinoma), and a further positron emission tomography/computed tomography visualised this lesion. He was deemed unsuitable for further intervention and underwent palliative radiotherapy for symptom control. CONCLUSION: This case represents the first reported isolated pituitary fossa metastasis from a tonsillar squamous cell carcinoma. A high degree of clinical suspicion is recommended, along with a low threshold for biopsy and a cautioned use of positron emission tomography/computed tomography, when investigating such patients.


Assuntos
Carcinoma de Células Escamosas/secundário , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Sela Túrcica/patologia , Neoplasias Tonsilares/patologia , Biópsia/métodos , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/métodos , Síndrome de Horner/diagnóstico , Síndrome de Horner/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/patologia , Recidiva Local de Neoplasia , Doenças do Nervo Oculomotor/diagnóstico , Doenças do Nervo Oculomotor/etiologia , Cuidados Paliativos/métodos , Radioterapia/métodos , Sela Túrcica/diagnóstico por imagem , Sela Túrcica/efeitos da radiação , Resultado do Tratamento
19.
Gac Med Mex ; 156(2): 103-108, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32285852

RESUMO

Squamous cell carcinoma is the most common head & neck malignancy, and its first descriptions date from the pharaonic era. It has impacted humanity by affecting labor, scientific and cultural productivity and, sometimes, it has influenced the course of history. Head & neck cancer is more common in economically impoverished countries and individuals; however, it can affect any socioeconomic stratum; it has been suffered by known, famous, economically powerful celebrities, intellectuals and artists. Head & neck cancer treatment has been controversial since its initial description up to the present day. Therapeutic decisions have been influenced not only by the stage but by the patient's environment and, sometimes, in an effort to reduce the morbidity resulting from the various oncological treatments, erroneous decisions have been made that have implied the loss of the patient's life. Unfortunately, currently we continue to see these behaviors. A synthesis of cases of renowned celebrities that suffered from this cancer is presented, and the impact this implied in the society of their times is described.


Assuntos
Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeça e Pescoço/terapia , Humanos
20.
Bull Cancer ; 107(5): 601-611, 2020 May.
Artigo em Francês | MEDLINE | ID: mdl-32305127

RESUMO

Sinonasal carcinomas account for 3% of ENT cancers. They are subdivided into squamous cell carcinomas (50%), adenocarcinomas [20%, mostly of intestinal type (ITAC)], and more rarely, adenoid cystic carcinomas, olfactory neuroblastomas (=esthesioneuroblastomas), neuroendocrine carcinomas or undifferentiated sinonasal carcinomas (SNUC). The 5-year survival rates are, in descending order, 72% for neuroblastomas, 63% for adenocarcinomas, 50-60% for large-cell neuroendocrine carcinomas, 53% for squamous cell carcinomas, 25-50% for adenoid cystic, 35% for small-cell neuroendocrine carcinomas and 35% for SNUC and newly discovered histologies. Surgery is the main treatment; endoscopic approaches reduce the morbidity with equivalent tumour control. Intensity-modulated radiation therapy (IMRT) is almost systematic. Nodal involvement is rare in ethmoidal adenocarcinomas and adenoid cystic carcinomas; it is intermediate and may justify prophylactic radiotherapy for N0 necks in SNUC, neuroblastoma, squamous cell carcinomas and sinonasal neuroendocrine carcinomas. IMRT or proton therapy is the mainstay of treatment of unresectable disease. Radiotherapy optimization by carbon ion therapy for adenoid cystic carcinomas, or by chemotherapy for all carcinomas with IMRT or proton therapy, is investigated within clinical trials in France. Neoadjuvant chemotherapy is reserved for rapidly progressive disease or histologies with a high metastatic potential such as neuroendocrine carcinomas or SNUC. Given their histologic and molecular specificities and different relapse patterns, an expertise of the REFCOR network, with REFCORpath review, is likely to correct diagnoses, rectify treatments, with an impact on survival.


Assuntos
Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias dos Seios Paranasais , Doenças Raras , Adenocarcinoma/classificação , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidade , Adenocarcinoma/terapia , Carcinoma Adenoide Cístico/diagnóstico , Carcinoma Adenoide Cístico/mortalidade , Carcinoma Adenoide Cístico/terapia , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/mortalidade , Carcinoma Neuroendócrino/terapia , Carcinoma de Células Escamosas/classificação , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , Humanos , Neoplasias dos Seios Paranasais/classificação , Neoplasias dos Seios Paranasais/diagnóstico , Neoplasias dos Seios Paranasais/mortalidade , Neoplasias dos Seios Paranasais/terapia , Prognóstico , Doenças Raras/diagnóstico , Doenças Raras/mortalidade , Doenças Raras/terapia
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