RESUMEN
INTRODUCTION: Docetaxel plus ramucirumab (DTX + RAM) therapy is a standard treatment for previously treated lung cancer, but many adverse events have been reported. This retrospective study was conducted to examine if the side effects of DTX + RAM therapy can be minimized by the combined use of oral dexamethasone (DEX), and to assess the therapeutic effect of DTX + RAM in patients with recurrent lung cancer. METHODS: Forty patients with relapsed non-small cell lung cancer who underwent DTX + RAM therapy were divided into two groups based on the concomitant use of oral DEX, and the therapeutic effects and toxicities in the two groups were compared. RESULTS: The objective response rate (ORR) was significantly better in the DEX group (P = 0.0203). The median progression-free survival (PFS) was 5.20 months vs 2.87 months (P = 0.064) in the DEX and non-DEX groups, respectively. However, the median overall survival (OS) was significantly better in the DEX group (15.17 months vs 7.37 months, P = 0.0317). The frequency of fluid retention within six months of the start of treatment was 10.0% vs 42.5% in the DEX and non-DEX groups, respectively, with the fluid retention rate being significantly higher in the non-DEX group (P = 0.039).Conclusion: Concomitant use of oral DEX during DTX + RAM therapy may facilitate the long-term continuation of treatment and contribute to OS prolongation.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Pulmón de Células no Pequeñas , Dexametasona , Docetaxel , Neoplasias Pulmonares , Ramucirumab , Humanos , Docetaxel/administración & dosificación , Docetaxel/uso terapéutico , Masculino , Femenino , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico , Estudios Retrospectivos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Persona de Mediana Edad , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Anciano , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Adulto , Administración Oral , Recurrencia Local de Neoplasia/tratamiento farmacológico , Resultado del TratamientoRESUMEN
BRCA1/2 genetic testing has become clinically important in breast cancer care, but increasing demand may put a burden on the shortage of healthcare professionals. We performed a single-center, pilot randomized controlled study to assess the effectiveness of employing a video educational tool that included standard pre-test genetic counseling elements related to BRCA1/2. Patients with operable breast cancer who met the criteria for genetic testing based on age, sex, subtype, and family history were recruited. Sixty consenting participants were randomized 1:1 and placed in groups that received either traditional face-to-face pre-test counseling or video-viewing and face-to-face decisional support. To assess decisional conflict in the participants, surveys based on the Decisional Conflict Scale (DCS) were administered two times, once immediately after intervention and again 2-4 weeks later. The time taken for counseling and confirmation of whether the participants had undergone testing were also recorded. The difference in the total DCS scores between the two groups was not significantly different for either of the survey periods, and there was no significant difference in the number of participants who underwent testing (23/30 [76.7%] vs. 26/30 [86.7%]; p = 0.51). However, the "effective decision" subscale score was significantly higher in the video group 2-4 weeks after counseling (31.01 ± 16.82 vs. 21.43 ± 16.09; p = 0.04 [mean ± SD]). The time taken for counseling was significantly shorter in the video group (8.00 ± 4.5 vs. 27.00 ± 7.61 min; p < 0.001 [median ± SD]). Our findings indicate the potential benefit of the video educational tool for providing BRCA1/2-related information. These tools may also enable healthcare professionals to spend more time supporting psychological issues. Notably, after some time, patients may question whether their decision was appropriate. Therefore, it is necessary to identify those in conflict and provide them with proper support.
RESUMEN
Intracytoplasmic sperm injection (ICSI) is an alternative technique to in vitro fertilization (IVF) for producing transferable blastocysts, especially in combination with cryopreserved oocytes, when the IVF system does not work sufficiently. The present study was conducted to directly compare the efficacy of producing bovine blastocysts by ICSI and IVF from vitrified-warmed and fresh oocytes. Denuded oocytes with a detectable first polar body were vitrified-warmed using a nylon mesh device. In the non-vitrified control group, blastocyst yields 8 days after IVF and ICSI were 32.0 and 26.8%, respectively. Oocyte vitrification and subsequent IVF resulted in an impaired blastocyst yield (15.0%); however, such a loss of efficacy due to vitrification was not observed in the ICSI group (blastocyst yield, 25.2%). The alignment of cortical granules beneath the oolemma was comparable between the fresh control and vitrified-warmed oocytes. Here, we report the high survival of vitrified-warmed bovine oocytes, as assessed by ICSI.
Asunto(s)
Nylons , Inyecciones de Esperma Intracitoplasmáticas , Animales , Blastocisto , Bovinos , Criopreservación/métodos , Criopreservación/veterinaria , Fertilización In Vitro/veterinaria , Masculino , Oocitos , Semen , Inyecciones de Esperma Intracitoplasmáticas/métodos , Inyecciones de Esperma Intracitoplasmáticas/veterinaria , VitrificaciónRESUMEN
Ataxia-telangiectasia mutated (ATM) functions as a key initiator and coordinator of DNA damage and cellular stress responses. ATM signaling pathways contain many downstream targets that regulate multiple important cellular processes, including DNA damage repair, apoptosis, cell cycle arrest, oxidative sensing, and proliferation. Over the past few decades, associations between germline ATM pathogenic variants and cancer risk have been reported, particularly for breast and pancreatic cancers. In addition, given that ATM plays a critical role in repairing double-strand breaks, inhibiting other DNA repair pathways could be a synthetic lethal approach. Based on this rationale, several DNA damage response inhibitors are currently being tested in ATM-deficient cancers. In this review, we discuss the current knowledge related to the structure of the ATM gene, function of ATM kinase, clinical significance of ATM germline pathogenic variants in patients with hereditary cancers, and ongoing efforts to target ATM for the benefit of cancer patients.
Asunto(s)
Proteínas de la Ataxia Telangiectasia Mutada/genética , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Predisposición Genética a la Enfermedad , Neoplasias/etiología , Neoplasias/metabolismo , Animales , Apoptosis/genética , Proteínas de la Ataxia Telangiectasia Mutada/química , Ciclo Celular/genética , Roturas del ADN de Doble Cadena , Daño del ADN , Reparación del ADN , Manejo de la Enfermedad , Regulación de la Expresión Génica , Mutación de Línea Germinal , Humanos , Neoplasias/diagnóstico , Neoplasias/terapia , Oxidación-Reducción , Estrés Oxidativo , Medicina de Precisión , Transducción de SeñalRESUMEN
INTRODUCTION: The development of new xanthine oxidase (XO) inhibitors, such as febuxostat and topiroxostat, could offer an alternative to treatment with allopurinol. The purpose of this study was to compare safety profiles of new XO inhibitors with allopurinol using a spontaneous reporting system database. MATERIALS AND METHODS: A retrospective pharmacovigilance disproportionality analysis was conducted using the Japanese Adverse Drug Event Report database. Adverse event reports submitted to the Pharmaceuticals and Medical Devices Agency were analyzed, and the reporting odds ratio (ROR) and 95% confidence interval (CI) for each adverse event were calculated. RESULTS: Among 7,305 reports of adverse events associated with XO inhibitors, 64.5% involved males, who were frequently in their 70s (25.9%). A large number of skin-related adverse events were detected with the use of allopurinol, but not with febuxostat or topiroxostat. As for individual XO inhibitors, the signal values showing associations between drug reaction with eosinophilia and systemic symptoms (DRESS) and allopurinol, drug-induced liver injury and febuxostat, and blood urea increase and topiroxostat were noteworthy. CONCLUSION: The strength of the associations of XO inhibitors with adverse events is variable, and further studies are required to evaluate the identified signals.
Asunto(s)
Febuxostat , Xantina Oxidasa , Alopurinol/efectos adversos , Febuxostat/efectos adversos , Humanos , Masculino , Mercadotecnía , Estudios RetrospectivosRESUMEN
BACKGROUND/AIMS: Despite the high prevalence of obstructive sleep apnea syndrome (OSAS), most individuals are unaware of its diagnosis. We assessed whether an upper gastrointestinal (GI) endoscopy can accurately predict the incidence of OSAS. METHODS: After endoscopic evaluation of laryngo-pharyngeal collapse, a total of 154 subjects with laryngo-pharyngeal collapse and 52 control subjects underwent polysomnography. Based on the modified Fujita Classification, upper airway obstruction was classified into 3 different types: oropharyngeal, supraglottic and combined type, and associations between upper airway obstruction and OSAS were evaluated. RESULTS: Of 154 subjects with laryngo-pharyngeal collapse, 108 (70.1%) were diagnosed as OSAS, while only 4 (7.7%) control subjects were diagnosed as OSAS (p < 0.001). The sensitivity and specificity of endoscopic diagnosis were 96.4 and 51.1%, respectively. Oropharyngeal involvement was frequently found in 90.2% of the subjects (139/154). The severity of upper airway obstruction was significantly correlated with the apnea-hypopnea index score (r = 0.55, p < 0.001). A multivariate logistic regression analysis revealed that a male sex (OR 5.20; 95% CI 2.65-10.2, p < 0.001), body mass index ≥25 kg/m2 (OR 4.98; 95% CI 2.23-11.2, p = 0.02) and severe obstruction (OR 7.79; 95% CI 3.34-18.2, p < 0.001) were significant independent predictors of severe OSAS. CONCLUSION: A conventional upper GI endoscopic examination might be useful as a diagnostic modality for OSAS.
Asunto(s)
Obstrucción de las Vías Aéreas/diagnóstico por imagen , Endoscopía del Sistema Digestivo , Apnea Obstructiva del Sueño/diagnóstico , Anciano , Obstrucción de las Vías Aéreas/complicaciones , Obstrucción de las Vías Aéreas/epidemiología , Estudios Transversales , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Polisomnografía , Estudios Retrospectivos , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/etiología , Tokio/epidemiologíaRESUMEN
Metastasis is the leading cause of cancer death. A tumor-supportive microenvironment, or premetastatic niche, at potential secondary tumor sites plays an important role in metastasis, especially in tumor cell colonization. Although a fibrotic milieu is known to promote tumorigenesis and metastasis, the underlying molecular contributors to this effect have remained unclear. Here we show that periostin, a component of the extracellular matrix that functions in tissue remodeling, has a key role in formation of a fibrotic environment that promotes tumor metastatic colonization. We found that periostin was widely expressed in fibrotic lesions of mice with bleomycin-induced lung fibrosis, and that up-regulation of periostin expression coincided with activation of myofibroblasts positive for α-smooth muscle actin. We established a lung metastasis model for B16 murine melanoma cells and showed that metastatic colonization of the lung by these cells was markedly promoted by bleomycin-induced lung fibrosis. Inhibition of periostin expression by giving an intratracheal antisense oligonucleotide targeting periostin mRNA was found to suppress bleomycin-induced lung fibrosis and thereby to attenuate metastatic colonization of the lung by melanoma cells. Our results indicate that periostin is a key player in the development of bleomycin-induced fibrosis and consequent enhancement of tumor cell colonization in the lung. Our results therefore implicate periostin as a potential target for prevention or treatment of lung metastasis.
Asunto(s)
Bleomicina/efectos adversos , Moléculas de Adhesión Celular/antagonistas & inhibidores , Neoplasias Pulmonares/secundario , Melanoma Experimental/patología , Oligonucleótidos Antisentido/administración & dosificación , Fibrosis Pulmonar/terapia , Actinas/metabolismo , Animales , Moléculas de Adhesión Celular/genética , Línea Celular Tumoral , Matriz Extracelular/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Melanoma Experimental/genética , Melanoma Experimental/metabolismo , Ratones , Oligonucleótidos Antisentido/farmacología , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/genética , Fibrosis Pulmonar/metabolismo , Microambiente Tumoral , Regulación hacia Arriba , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND AND AIM: Multi-detector-row computed tomography (MDCT) has been reported to be a potentially useful modality for detection of the bleeding origin in patients with acute upper massive gastrointestinal (GI) bleeding. The purpose of this study is to investigate the efficacy of MDCT as a routine method for detecting the origin of acute upper GI bleeding prior to urgent endoscopy. METHODS: Five hundred seventy-seven patients with acute upper GI bleeding (514 nonvariceal patients, 63 variceal patients) who underwent urgent upper GI endoscopy were retrospectively analyzed. Patients were divided into three groups: enhanced MDCT, unenhanced MDCT, and no MDCT before endoscopy. The diagnostic accuracy of MDCT for detection of the bleeding origin was evaluated, and the average procedure times needed to endoscopically identify the bleeding origin were compared between groups. RESULTS: Diagnostic accuracy among endoscopists was 55.3% and 14.7% for the enhanced MDCT and unenhanced MDCT groups, respectively. Among nonvariceal patients, accuracy was 50.2% in the enhanced MDCT group, which was significantly better than that in the unenhanced MDCT group (16.5%). In variceal patients, accuracy was significantly better in the enhanced MDCT group (96.4%) than in the unenhanced MDCT group (0.0%). These accuracies were similar to those achieved by expert radiologists. The average procedure time to endoscopic detection of the bleeding origin in the enhanced MDCT group was significantly faster than that in the unenhanced MDCT and no-MDCT groups. CONCLUSIONS: Enhanced MDCT preceding urgent endoscopy may be an effective modality for the detection of bleeding origin in patients with acute upper GI bleeding.
Asunto(s)
Atención Ambulatoria , Endoscopía Gastrointestinal , Hemorragia Gastrointestinal/diagnóstico por imagen , Hemorragia Gastrointestinal/cirugía , Tomografía Computarizada Multidetector , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/diagnóstico por imagen , Femenino , Hemorragia Gastrointestinal/etiología , Humanos , Masculino , Persona de Mediana Edad , Intensificación de Imagen Radiográfica , Sensibilidad y Especificidad , Adulto JovenRESUMEN
BACKGROUND: Diagnosis of pulmonary tuberculosis is usually made by diagnostic imaging such as chest X-ray or computed tomography (CT), and sputum test including smear and polymerase chain reaction (PCR) test. However there is difficulty in making diagnose when atypical imaging and negative sputum test are presented, followed by diagnostic delay. CASE: A 26-year-old man from Philippines consulted other clinic because of dry cough and was pointed out mass shadow in right upper lung field in his chest CT. He visited our office because of positive interferon gamma release assay, but repeated sputum test could not find tuberculosis. Bleeding from mass lesion failed to perform biopsy by bronchoscope, and we failed to find tuberculosis by smear and PCR test from bronchial brushing and wash. Transthoracic needle biopsy from his mass lesion revealed multiple non-caseous granuloma, and lead to make a decision about starting medication. Four weeks later sputum culture from his first visit revealed positive, and diagnosis of tuberculosis was made. DISCUSSION: For avoiding therapy delay it is important to perform invasive diagnostic procedure including histological examination and clinical decision of starting medication, when conservative diagnostic procedure such as sputum test or diagnostic imaging present atypical finding for diagnosing tuberculosis.
Asunto(s)
Diagnóstico Diferencial , Neoplasias Pulmonares/diagnóstico , Tuberculosis Pulmonar/diagnóstico , Adulto , Diagnóstico Tardío , Humanos , Masculino , Imagen Multimodal , Radiografía Torácica , Tomografía Computarizada por Rayos XRESUMEN
A 53-year-old female who complained of constipation and abdominal fullness was referred to our hospital. A tender low abdominal mass was palpable. Imaging (abdominal ultrasonography, CT, and MRI) revealed that the tumor had spread to the mesosigmoid and the superior mesentery. The tumor was very difficult to diagnose on the basis of imaging alone. Therefore, we obtained a biopsy at the time of laparotomy for definitive diagnosis. The biopsy showed extensive fibrosis and lymphocyte, plasma cell, and eosinophil infiltration in the associated adipose tissue. Sclerosing mesenteritis was diagnosed. The patient's symptoms improved immediately after initiating steroid therapy. Pathological examination and empirical steroid therapy are useful for the diagnosis and medical treatment of sclerosing mesenteritis, respectively.
Asunto(s)
Paniculitis Peritoneal/tratamiento farmacológico , Paniculitis Peritoneal/patología , Esteroides/uso terapéutico , Biopsia , Femenino , Humanos , Laparotomía , Imagen por Resonancia Magnética , Persona de Mediana Edad , Imagen Multimodal , Tomografía Computarizada por Rayos XRESUMEN
A 50-year-old woman presented with left pleural effusion. A pleural fluid cell-block specimen and longitudinal lymph node needle biopsy suggested signet ring cell carcinoma (SRCC). Although computed tomography showed a consolidation shadow in the left lower lobe, a left lung biopsy could not be performed. Upper gastrointestinal endoscopy revealed no malignancies. We administered carboplatin, pemetrexed, ipilimumab, and nivolumab for lung cancer; however, she died due to progressive respiratory failure. Pathological autopsy revealed that the left pleura was thickened as in mesothelioma, based on which pseudomesotheliomatous carcinoma of the lung (PMCL) was diagnosed. PMCLs exhibiting an SRCC morphology are rare.
Asunto(s)
Carcinoma de Células en Anillo de Sello , Neoplasias Pulmonares , Mesotelioma Maligno , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Pulmonares/patología , Autopsia , Pulmón/patologíaRESUMEN
Background/Aim: Certain germline pathogenic variants (PVs), known as founder mutations, have been frequently observed in specific regions and ethnic groups. In Japan, several pathogenic variants of BRCA1/2 have been identified as founder mutations, with their distribution varying across different regions. This retrospective study aimed to further investigate the detailed distribution and correlation between genotype and clinical features among breast cancer patients. Patients and Methods: This study was conducted at Kobe University Hospital and three collaborating institutions. It included breast cancer patients who underwent BRCA1/2 genetic testing between July 1, 2018, and March 31, 2021, and were found to have germline PVs. Clinical characteristics and breast cancer subtypes were compared between carriers of BRCA2 c.5576_5579del and those with other PVs. Additionally, the detection rate of BRCA2 c.5576_5579del was compared with that observed in a previous report. Results: A total of 38 breast cancer patients were included; PVs in BRCA1 and BRCA2 were detected in 12 and 26 patients, respectively, 12 of whom were BRCA2 c.5576_5579del carriers. BRCA2 c.5576_5579del carriers were more likely to develop triple negative breast cancers among all BRCA2 PV carriers. BRCA2 c.5576_5579del accounted for 30.8% of the PVs detected, with a particularly high frequency of 72.7% at Kakogawa Central City Hospital. Conclusion: BRCA2 c.5576_5579del was detected with a particularly high frequency in Hyogo Prefecture, especially in Kakogawa city. In the future, a survey of the distribution of the BRCA2 c.5576_5579del carriers may provide more clarity regarding their localization.
RESUMEN
OBJECTIVE: To analyze the factors prognostic of survival in patients with advanced epithelial ovarian cancer (EOC) treated with neoadjuvant chemotherapy (NAC) followed by interval debulking surgery. METHODS: Outcomes were retrospectively in patients with advanced EOC or peritoneal cancer who received neoadjuvant paclitaxel and carboplatin chemotherapy every 3 weeks for three to four cycles, followed by interval debulking surgery and three additional cycles of the same regimens from January 2001 to November 2010. Therapeutic response was assessed histopathologically as grade 0 to 3, based on the degree of disappearance of cancer cells, displacement by necrotic and fibrotic tissue, and tumor-induced inflammation. Factors prognostic of progression-free survival (PFS) and overall survival (OS) were calculated. RESULTS: The 124 enrolled patients had a median age of 62 years (range, 35-79 years). Viable cancer cells were observed in specimens resected from 72 patients (58%) at interval debulking surgery after NAC. Multivariate analysis using the Cox proportional hazard model showed that advanced (stage IV) disease (hazard ratio [HR]=1.94, p=0.003), residual cancer at the end of surgery ≥1cm (HR=3.78, p<0.001), and histological grade 0-1 (HR=1.65, p=0.03) were independent predictors of decreased OS. Grade 0-1 was also an independent predictor of increased risk of relapse within 6 months (odds ratio=8.42, p=0.003). CONCLUSIONS: Residual disease of ≥1cm, advanced stage, and the presence of more viable disease in resected specimens are prognostic factors for survival in advanced EOC patients receiving NAC followed by interval debulking surgery.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Glandulares y Epiteliales/terapia , Neoplasias Ováricas/patología , Neoplasias Ováricas/terapia , Adulto , Anciano , Carboplatino/administración & dosificación , Carcinoma Epitelial de Ovario , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Clasificación del Tumor , Estadificación de Neoplasias , Neoplasia Residual , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Glandulares y Epiteliales/cirugía , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Paclitaxel/administración & dosificación , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/cirugía , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: Cervical cancer is the second most common cancer in females worldwide, and the majority of squamous cell carcinomas and adenocarcinomas are associated with high-risk human papillomavirus (HPV) infection. However, the relationship between clear cell carcinoma of the cervix (CCCC) and HPV is unclear. In this study, we sought to determine if HPV infection is associated with CCCC and to elucidate the signaling pathways involved. METHODS: We collected samples from 13 CCCC patients and collated the relevant clinicopathologic data. We then evaluated the presence of HPV types 16, 18, 31, 33, 35, 52, and 58 by broad-spectrum amplification by polymerase chain reaction and HPV types 39, 45, 51, 56, 59, and 68 by nested polymerase chain reaction assay that combines degenerate E6/E7 consensus primers and type-specific primers from extracted genomic DNA. Immunohistochemistry was used to analyze the expression of EGFR (epidermal growth factor receptor), HER2, PTEN (phosphatase and tensin homolog), phospho-AKT, phospho-mTOR (mammalian target of rapamycin), p16, and p53. EGFR and HER2 gene amplification was determined by fluorescence in situ hybridization. RESULTS: Patients with stage IB CCCC had a better 3-year overall survival rate compared with those with advanced-stage cancer (100% vs 44%; P = 0.014). High-risk HPVs were not detected in any of the cases examined. EGFR immunostaining was observed in 9 (75%) of 12 patients, HER2 in 3 (25%) of 12, PTEN in 6 (50%) of 12, and phospho-AKT in 7 (58%) of 12, and phospho-mTOR in 6 (50%) of 12. EGFR amplification could not be detected, but HER2 amplification was identified in 1 of (12.5%) 8 cases. CONCLUSIONS: Patients with stage I CCCC demonstrated good overall survival and rare recurrence. Clear cell carcinoma of the cervix is unrelated to high-risk HPV infection; hence, current vaccines will not prevent the incidence of CCCC. However, increased EGFR or HER2 expression or activation of AKT or mTOR was observed in all cases, indicating that inhibitors of tyrosine kinases or the AKT-mTOR pathway may be suitable treatment regimens for CCCC.
Asunto(s)
Adenocarcinoma de Células Claras/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Papillomaviridae/genética , Infecciones por Papillomavirus/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Adenocarcinoma de Células Claras/mortalidad , Adenocarcinoma de Células Claras/patología , Adenocarcinoma de Células Claras/virología , Adulto , Anciano , Anciano de 80 o más Años , ADN Viral/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Femenino , Estudios de Seguimiento , Amplificación de Genes , Humanos , Técnicas para Inmunoenzimas , Hibridación Fluorescente in Situ , Metástasis Linfática , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/virología , Estadificación de Neoplasias , Fosfohidrolasa PTEN/metabolismo , Infecciones por Papillomavirus/mortalidad , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Fosforilación , Reacción en Cadena de la Polimerasa , Pronóstico , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Estudios Retrospectivos , Factores de Riesgo , Transducción de Señal , Tasa de Supervivencia , Serina-Treonina Quinasas TOR/metabolismo , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virologíaRESUMEN
PURPOSE: Endometrial stromal sarcomas (ESSs) are rare tumors and are divided into two groups: low-grade endometrial stromal sarcoma (ESS-LG) and undifferentiated endometrial sarcoma (UES). The purpose of this study was to compare the clinicopathological features and immunophenotypes of ESS-LG and UES. METHODS: The authors evaluated 16 patients diagnosed with ESS at the Hyogo Cancer Center, reviewed their files and data, and performed an immunohistochemical study for oncogenic proteins (EGFR, PDGFR-α, and PDGFR-ß) and cell cycle regulators (cyclin D1, cyclin E, p16(INK4a), p21(cip1), p27(kip1), and p53) to compare ESS-LG and UES using the World Health Organization (WHO) classification. RESULTS: Four cases (25 %) were classified as ESS-LGs and 12 (75 %) as UES. Patients with UES had a significantly worse overall survival than did those with ESS-LG (p = 0.0445). Although no ESS-LGs showed expression of p16(INK4a), 10 of 12 (83 %) UESs showed expression of p16(INK4a). UESs showed a trend toward higher expression of cyclin D1, p21(cip1), and p53 compared with ESS-LGs. CONCLUSIONS: Our data emphasize the clinical importance of the WHO classification of ESS. It is of utmost importance to establish a proper classification to increase the consistency of data that may be useful for improving clinical and therapeutic management of patients with ESS.
Asunto(s)
Tumores Estromáticos Endometriales/metabolismo , Tumores Estromáticos Endometriales/patología , Sarcoma/metabolismo , Sarcoma/patología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante , Ciclina D1/metabolismo , Ciclina E/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Diagnóstico Diferencial , Supervivencia sin Enfermedad , Tumores Estromáticos Endometriales/terapia , Receptores ErbB/metabolismo , Femenino , Humanos , Histerectomía , Inmunohistoquímica , Estimación de Kaplan-Meier , Escisión del Ganglio Linfático , Persona de Mediana Edad , Clasificación del Tumor , Ovariectomía , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Salpingectomía , Sarcoma/terapia , Estadísticas no Paramétricas , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
BACKGROUND: Pegfilgrastim is recommended in docetaxel plus ramucirumab (DTX + RAM) therapy for recurrent nonsmall cell lung cancer (NSCLC) because of the associated frequency of febrile neutropenia (FN). However, the FN occurs less frequently when the dose of DTX is reduced because of other adverse events, such as appetite loss and oral mucositis. METHODS AND RESULTS: Twenty-two patients with recurrent NSCLC who received DTX + RAM therapy at the Hiroshima Prefectural Hospital. The cut-off value which is the most unlikely to cause FN without the combined use of pegfilgrastim was set using a receiver operating characteristic (ROC) curve. This was created according to the dose of DTX and the presence or absence of the onset of FN. We compared the incidence of FN when a DTX dose above and below the cut-off value was used. The ROC curve showed that 48 mg/m2 was the best cut-off value that predicted whether FN was likely to occur when pegfilgrastim was not used concurrently. The incidence of FN was 26.1% for DTX ≥48 mg/m2 and 5.1% for DTX <48 mg/m2 . CONCLUSIONS: Pegfilgrastim can be discontinued when the dose of DTX is reduced to <48 mg/m2 due to nonhematological toxicities.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Docetaxel , Reducción Gradual de Medicamentos , Neoplasias Pulmonares/tratamiento farmacológico , RamucirumabRESUMEN
BACKGROUND: Few studies have been conducted on comprehensive genomic profiling (CGP) panels in Japanese patients with thoracic malignancies after completing standard treatment. Consequently, its value in clinical practice remains unclear. METHODS: We conducted a retrospective study of Japanese patients with thoracic malignancies who underwent CGP between June 2019 and November 2022 at our hospital. We evaluated the detection rate of actionable genetic alterations and percentage of patients who received genomically-matched therapy. Furthermore, we examined the value of the CGP panel in patients who underwent multiplex gene-panel testing prior to their initial treatment. This study was performed in accordance with the principles of the Declaration of Helsinki. RESULTS: The study included 56 patients, of whom 47 (83.9%) had actionable genetic alterations and 8 (14.3%) received genomically-matched therapy. Of these, four patients were treated with approved drugs and three patients were treated with investigational agents. In addition, one patient was treated with approved drugs using the patient-directed care system. Of the 17 patients who had multiplex gene-panel testing performed at the start of their initial therapy, two (11.8%) were newly identified by the CGP panel and subsequently received genomically-matched therapy. EGFR L718Q and MET amplification were observed in two of the seven patients with epidermal growth factor receptor-tyrosine kinase inhibitor resistance. CONCLUSIONS: The CGP panel could identify genetic alterations, thereby facilitating genomically-matched therapy, even in patients with thoracic malignancies who could not be identified using multiplex gene-panel testing.
Asunto(s)
Neoplasias Pulmonares , Neoplasias Torácicas , Humanos , Estudios Retrospectivos , Pueblos del Este de Asia , Neoplasias Pulmonares/patología , Neoplasias Torácicas/genética , GenómicaRESUMEN
OBJECTIVE: The purpose of this study was to compare surgical outcomes using modified (type II) and traditional (type III) abdominal radical trachelectomy (ART) for fertility-sparing surgery in early cervical cancer. METHODS: A prospectively maintained database of ART procedures was analyzed. Data were collected regarding age, stage, histology, operative outcome, surgical complication, and fertility outcome. RESULTS: We performed 23 fertility-sparing ARTs for patients with International Federation of Gynecology and Obstetrics stages IA to IB1 tumors of less than 2 cm between 2006 and 2010. Type III ART was attempted in 8 patients and modified ART in 15 patients. The median operating time was greater in the type III group compared with that in the type II group (305 vs 247 minutes; P < 0.02). The median surgical blood loss was greater in the type III ART group (580 mL; range, 250-988 mL) compared with that in the modified type II group (366 mL; range, 200-850 mL; P < 0.05). The median time to recovery of bladder dysfunction was less in the type II group (9 days; range, 3-10 days) than that in the type III group (13 days; range, 10-23 days; P < 0.01). There were no recurrences at the time of this report. CONCLUSIONS: Type II ART provides surgical and pathological outcomes with better recovery of bladder function similar to those in type III ART. For patients with early cervical cancer who wish to preserve reproductive function, type II ART is a feasible and safe operation.
Asunto(s)
Cavidad Abdominal/cirugía , Adenocarcinoma/cirugía , Preservación de la Fertilidad/métodos , Procedimientos Quirúrgicos Ginecológicos/métodos , Neoplasias del Cuello Uterino/cirugía , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Adulto , Detección Precoz del Cáncer , Estudios de Factibilidad , Femenino , Humanos , Estadificación de Neoplasias , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/patologíaRESUMEN
Peritoneal dissemination of ovarian cancer (OC) correlates with poor prognosis, but the mechanisms underlying the escape of OC cells from the intraperitoneal immune system have remained unknown. We here identify pigment epithelium-derived factor (PEDF) as a promoting factor of OC dissemination, which functions through induction of CD206+ Interleukin-10 (IL-10)-producing macrophages. High PEDF gene expression in tumors is associated with poor prognosis in OC patients. Concentrations of PEDF in ascites and serum are significantly higher in OC patients than those with more benign tumors and correlated with early recurrence of OC patients, suggesting that PEDF might serve as a prognostic biomarker. Bromodomain and extraterminal (BET) inhibitors reduce PEDF expression and limit both OC cell survival and CD206+ macrophage induction in the peritoneal cavity. Our results thus implicate PEDF as a driver of OC dissemination and identify a BET protein-PEDF-IL-10 axis as a promising therapeutic target for OC.
Asunto(s)
Neoplasias Ováricas , Serpinas , Proteínas del Ojo , Femenino , Humanos , Interleucina-10/metabolismo , Macrófagos/metabolismo , Factores de Crecimiento Nervioso , Neoplasias Ováricas/metabolismo , Serpinas/genética , Serpinas/metabolismoRESUMEN
BACKGROUND: Several studies reported that abnormal behavior was noted in pediatric patients receiving several drugs, including neuraminidase inhibitors (NIs). However, the information on drugs associated with abnormal behavior in a real-world setting remains limited. The purpose of this study was to clarify the drugs associated with abnormal behavior using a spontaneous reporting system database. METHODS: We performed a retrospective pharmacovigilance disproportionality analysis using the Japanese Adverse Drug Event Report database. Adverse event reports submitted to the Pharmaceuticals and Medical Devices Agency were analyzed, and the reporting odds ratio at 95% confidence interval were calculated. RESULTS: A total of 1,144 reports of abnormal behavior were identified. The signals were detected through the association of 4 neuraminidase inhibitors (oseltamivir, zanamivir, laninamivir, and peramivir) with the abnormal behaviour. These signals were stronger for oseltamivir than other neuraminidase inhibitors. The signals were also detected for acetaminophen and montelukast. CONCLUSION: Our results should be able to raise physicians' awareness of drugs associated with abnormal behavior, but further investigation of these medications is warranted.