RESUMO
In humans, the adaptive immune system uses the exchange of information between cells to detect and eliminate foreign or damaged cells; however, the removal of unwanted cells does not always require an adaptive immune system1,2. For example, cell selection in Drosophila uses a cell selection mechanism based on 'fitness fingerprints', which allow it to delay ageing3, prevent developmental malformations3,4 and replace old tissues during regeneration5. At the molecular level, these fitness fingerprints consist of combinations of Flower membrane proteins3,4,6. Proteins that indicate reduced fitness are called Flower-Lose, because they are expressed in cells marked to be eliminated6. However, the presence of Flower-Lose isoforms at a cell's membrane does not always lead to elimination, because if neighbouring cells have similar levels of Lose proteins, the cell will not be killed4,6,7. Humans could benefit from the capability to recognize unfit cells, because accumulation of damaged but viable cells during development and ageing causes organ dysfunction and disease8-17. However, in Drosophila this mechanism is hijacked by premalignant cells to gain a competitive growth advantage18. This would be undesirable for humans because it might make tumours more aggressive19-21. It is unknown whether a similar mechanism of cell-fitness comparison is present in humans. Here we show that two human Flower isoforms (hFWE1 and hFWE3) behave as Flower-Lose proteins, whereas the other two isoforms (hFWE2 and hFWE4) behave as Flower-Win proteins. The latter give cells a competitive advantage over cells expressing Lose isoforms, but Lose-expressing cells are not eliminated if their neighbours express similar levels of Lose isoforms; these proteins therefore act as fitness fingerprints. Moreover, human cancer cells show increased Win isoform expression and proliferate in the presence of Lose-expressing stroma, which confers a competitive growth advantage on the cancer cells. Inhibition of the expression of Flower proteins reduces tumour growth and metastasis, and induces sensitivity to chemotherapy. Our results show that ancient mechanisms of cell recognition and selection are active in humans and affect oncogenic growth.
Assuntos
Canais de Cálcio/metabolismo , Proliferação de Células , Proteínas de Drosophila/metabolismo , Neoplasias/patologia , Isoformas de Proteínas/metabolismo , Animais , Canais de Cálcio/genética , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Drosophila melanogaster , Feminino , Técnicas de Silenciamento de Genes , Humanos , Masculino , Metástase Neoplásica , Neoplasias/tratamento farmacológico , Isoformas de Proteínas/genéticaRESUMO
BACKGROUND: The Safari study (UMIN000015168) was a retrospective, multicenter study in which 1072 consecutive cases of estrogen receptor-positive advanced breast cancer treated using 500 mg fulvestrant were registered. We previously reported the relationship between the patient factors and overall survival after the diagnosis using the same cases and the same factors for the analysis of time to treatment failure in patients with estrogen receptor-positive advanced breast cancer. The current study is an ad hoc analysis that focused on the relationship between the patient factors and overall survival after recurrence by adding factors generally associated with overall survival after recurrence. METHODS: The overall survival after recurrence in patients with estrogen receptor-positive human epidermal growth factor receptor 2 negative recurrent breast cancer was analyzed via univariate and multivariate analyses with a Cox proportional hazards model. RESULTS: A total of 598 cases were used for the analysis of overall survival after recurrence. Multivariate analysis revealed that favorable overall survival (median, 6.4 years) was significantly correlated with long time from recurrence to fulvestrant use (≥3 years), low nuclear or histological grade (G3 vs. G1), long time to treatment failure of initial palliative endocrine therapy (≥12 months) and long time to initial palliative chemotherapy (≥2 years). CONCLUSION: The results of this study indicate that sequential endocrine monotherapy may be a useful treatment option for patients with estrogen receptor-positive/human epidermal growth factor receptor 2 negative recurrent breast cancer who have been successfully treated with initial long-term palliative endocrine therapy.
Assuntos
Neoplasias da Mama , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Feminino , Fulvestranto/uso terapêutico , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Pós-Menopausa , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos RetrospectivosRESUMO
A 23-year-old woman was presented with fever and epigastric pain. Contrast enhanced computed tomography revealed a 40mm mass in the lateral segment. Blood tests showed the elevation of WBC and CRP. With the diagnosis of liver abscess, the antibiotics were administered, and the clinical findings were promptly improved. One year later, she complained of the same symptoms, and the mass had increased to 50mm in diameter. Percutaneous liver biopsy led to the diagnosis of fibrolamellar hepatocellular carcinoma.
Assuntos
Carcinoma Hepatocelular , Abscesso Hepático , Neoplasias Hepáticas , Feminino , Humanos , Adulto Jovem , Adulto , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Abscesso Hepático/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
Cancer cells require oxygen and nutrients for growth, making angiogenesis one of the essential components of tumor growth. Gangliosides, constituting membrane lipid rafts, regulate intracellular signal transduction and are involved in the malignancy of cancer cells. While endothelial cells, as well as cancer cells, express vast amounts of gangliosides, the precise function of endothelial gangliosides in angiogenesis remains unclear. In this study, we focused on gangliosides of vascular endothelial cells and analyzed their functions on tumor angiogenesis. In human breast cancer, GM3 synthase was highly expressed in vascular endothelial cells as well as immune cells. Angiogenesis increased in GM3S-KO mice. In BAEC, RNA interference of GM3S showed increased cellular invasion and oxidative stress tolerance through activation of ERK. In the breast cancer model, GM3-KO mice showed an increase in tumor growth and angiogenesis. These results suggest that the endothelial ganglioside GM3 regulates tumor angiogenesis by suppressing cellular invasion and oxidative stress tolerance in endothelial cells.
Assuntos
Células Endoteliais/metabolismo , Gangliosídeo G(M3)/metabolismo , Neovascularização Patológica/metabolismo , Animais , Bovinos , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Células Cultivadas , Estimativa de Kaplan-Meier , Neoplasias Mamárias Experimentais/irrigação sanguínea , Neoplasias Mamárias Experimentais/genética , Neoplasias Mamárias Experimentais/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , N-Acetilgalactosaminiltransferases/genética , N-Acetilgalactosaminiltransferases/metabolismo , Neovascularização Patológica/genética , Sialiltransferases/genética , Sialiltransferases/metabolismo , Carga Tumoral/genética , Polipeptídeo N-AcetilgalactosaminiltransferaseRESUMO
OBJECTIVES: Our newly developed brief collaborative care intervention program has been suggested to be effective in reducing breast cancer patients' unmet needs and psychological distress; however, there has been no controlled trial to investigate its effectiveness. The purpose of this study was to examine the effectiveness of the program in relation to patients' perceived needs and other relevant outcomes for patients including quality of life, psychological distress and fear of recurrence (Clinical trial register; UMIN-CTR, Clinical registration number; R5172). METHODS: Fifty-nine highly distressed breast cancer patients receiving adjuvant chemotherapy and/or hormonal therapy were randomly assigned either to a treatment as usual group or to a collaborative care intervention, consisting of four sessions that mainly included assessment of the patients' perceived needs, learning skills of problem-solving treatment for coping with unmet needs and psycho-education provided by trained nurses supervised by a psycho-oncologist. RESULTS: Although >80% of the eligible patients agreed to participate, and >90% of participants completed the intervention, there were no significant differences with regard to patients' needs, quality of life, psychological distress and fear of recurrence, both at 1 and 3 months after intervention. CONCLUSION: Newly developed brief collaborative care intervention program was found to be feasible and acceptable. The trial, however, failed to show the effectiveness of the program on patients' relevant subjective outcomes. Further intervention program having both brevity and sufficient intensity should be developed in future studies.
Assuntos
Neoplasias da Mama/psicologia , Comportamento Cooperativo , Medo/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/psicologia , Avaliação de Resultados em Cuidados de Saúde , Qualidade de Vida , Estresse PsicológicoRESUMO
PURPOSE: Taxane-associated acute pain syndrome (T-APS) reportedly occurs in approximately 70% of patients undergoing therapy. We have previously reported that additional dexamethasone (DEX) administration attenuates T-APS. The aim of this study was to reveal risk factor(s) associated with the incidence of T-APS under prophylactic DEX administration. METHODS: In total, 143 patients with breast cancer who received docetaxel (75 mg/m2) or paclitaxel (175 mg/m2)-containing treatment regimens were enrolled. DEX (4-8 mg) was orally administered on days 2-4. Risk factors for the incidence of ≥ G2 and all-grade T-APS, as well as T-APS incidence between taxane-containing regimens in the first cycle, were retrospectively evaluated. RESULTS: Approximately 90% of the patients received taxanes for adjuvant or neoadjuvant chemotherapy. Overall, 55% of patients administered 4 mg DEX, whereas 45% received 8 mg DEX. Pegfilgrastim was administered in 27% of patients. Incidence of ≥ G2 and all-grade T-APS was 23.8%, and 69.2%, respectively. Univariate and multivariate analyses revealed that administration of pegfilgrastim is an independent risk factor for the incidence of ≥ G2 and all-grade T-APS; age younger than 55 years is also a risk factor for all-grade T-APS. Moreover, the incidence of ≥ G2 and all-grade T-APS was 45.5% and 81.8% in a paclitaxel regimen, and 22.0% and 68.2% in docetaxel-including regimens, respectively, revealing increased tendency with paclitaxel administration, with no significant differences. CONCLUSION: Pegfilgrastim co-administration is an independent risk factor for ≥ G2 and all-grade T-APS, and age younger than 55 years is a risk factor of all-grade T-APS under prophylactic DEX administration.
Assuntos
Dor Aguda , Neoplasias da Mama , Taxoides , Dor Aguda/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/tratamento farmacológico , Hidrocarbonetos Aromáticos com Pontes , Dexametasona/uso terapêutico , Análise Fatorial , Feminino , Humanos , Pessoa de Meia-Idade , Paclitaxel , Estudos Retrospectivos , Fatores de Risco , Taxoides/efeitos adversosRESUMO
CT-P6 is a biosimilar of trastuzumab and is recommended to be administered for 30-90 min in subsequent maintenance infusions to prevent infusion-related reactions (IRRs). We administered CT-P6 for 30 min as the first injection and as an alternative to reference trastuzumab in the maintenance infusion and evaluated the safety of the administration. A total of 140 patients with breast or gastric cancer, who received a switch from tri-weekly reference trastuzumab to CT-P6 for 30 min in maintenance infusions, were retrospectively evaluated. Premedication was administered prior to an infusion of CT-P6 and a cytotoxic agent. However, premedication was not provided when CT-P6 was co-administered with pertuzumab or administered alone. The primary endpoint was the incidence of IRRs. The secondary endpoint was the incidence of diarrhea and skin toxicity. Ninety-five percent of the patients had breast cancer, and 44.3% had advance-stage cancer. The treatment included CT-P6 alone (17.9%) or with cytotoxic agents (23.6%), antihormonal drugs (25.7%), and pertuzumab (62.9%). Median administration time of trastuzumab at the switch was 13 administrations (range 2-140). Premedication was administered to 20.7% patients. One patient (0.7%) experienced grade 3 IRR. The frequency of diarrhea in the reference trastuzumab group and the CT-P6 group was 7.1 and 6.4%, respectively, and that of skin toxicity was 6.4 and 5.0%, respectively, without differences. In conclusion, we first demonstrated that an initial CT-P6 administration for 30 min during the switch from reference trastuzumab in maintenance infusion is an acceptable administration method.
Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Medicamentos Biossimilares/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Trastuzumab/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/efeitos adversos , Esquema de Medicação , Substituição de Medicamentos , Feminino , Humanos , Infusões Intravenosas , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Disease sites of female genital tract cancers of BRCA1/2-associated hereditary breast and ovarian cancer (HBOC) are less understood than non-hereditary cancers. We aimed to elucidate the disease site distribution of genital cancers in women with the germline BRCA1 and BRCA2 pathogenic variants (BRCA1+ and BRCA2+) of HBOC. For the primary disease site, the proportion of fallopian tube and peritoneal cancer was significantly higher in BRCA2+ (40.5%) compared with BRCA1+ (15.4%) and BRCA- (no pathogenic variant, 12.8%). For the metastatic site, the proportion of peritoneal dissemination was significantly higher in BRCA1+ (71.9%) than BRCA- (55.1%) and not different from BRCA2+ (71.4%). With one of the most extensive patients, this study supported the previous reports showing that the pathogenic variants of BRCA1/2 were involved in the female genitalia's disease sites.
Assuntos
Neoplasias da Mama , Neoplasias Ovarianas , Proteína BRCA1/genética , Proteína BRCA2 , Neoplasias da Mama/genética , Feminino , Predisposição Genética para Doença , Genitália Feminina , Humanos , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/genética , Prognóstico , Estudos RetrospectivosRESUMO
PURPOSE: To identify the conflicts between a career as a surgeon and pregnancy and childbirth for women in Japan. METHODS: The Japan Surgical Society conducted a nationwide survey on pregnancy and childbirth among its members who are women. The questionnaire included items regarding demography, working styles, and pregnancy and childbirth, including adverse events and harassment. RESULTS: The response rate was 29.9% (1068 responses, median age, 37 years). Among the responders, 61% were married and 47% had children (average number of children, 1.7). Half of the respondents reported having experienced sexual harassment and 62% reported having received unwelcome comments about pregnancy. About 20% had undergone fertility treatment. In total, 51% had pregnancies, with miscarriages in 33% of these. The top answer for the best timing for pregnancy and childbirth was after becoming board-certified. Nearly one-third of first-time mothers experienced adverse events during pregnancy and delivery, and 28% quit or changed their job because of their pregnancy and the birth of their first child. CONCLUSIONS: Japanese women who choose a career as a surgeon face obstacles during pregnancy and childbirth. It is vital to share the findings of this study and understand the issues associated with pregnancy and childbirth regardless of gender. Interventions are essential to ensure that every pregnant surgeon has a safe working environment to allow unobstructed development of her career.
Assuntos
Escolha da Profissão , Cirurgia Geral/organização & administração , Saúde Ocupacional , Estresse Ocupacional/psicologia , Parto/psicologia , Médicas/psicologia , Gravidez/psicologia , Gravidez/estatística & dados numéricos , Sociedades Médicas/organização & administração , Cirurgiões/psicologia , Inquéritos e Questionários , Local de Trabalho/psicologia , Adulto , Feminino , Humanos , Japão , Assédio Sexual/psicologiaRESUMO
Polyglutamine diseases are a class of neurodegenerative diseases associated with the accumulation of aggregated mutant proteins. We previously developed a class of degradation-inducing agents targeting the ß-sheet-rich structure typical of such aggregates, and we showed that these agents dose-, time-, and proteasome-dependently decrease the intracellular level of mutant huntingtin with an extended polyglutamine tract, which correlates well with the severity of Huntington's disease. Here, we demonstrate that the same agents also deplete other polyglutamine disease-related proteins: mutant ataxin-3 and ataxin-7 in cells from spino-cerebellar ataxia patients, and mutant atrophin-1 in cells from dentatorubral-pallidoluysian atrophy patients. Targeting cross-ß-sheet structure could be an effective design strategy to develop therapeutic agents for multiple neurodegenerative diseases.
Assuntos
Ataxina-3/antagonistas & inibidores , Ataxina-7/antagonistas & inibidores , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Proteínas Repressoras/antagonistas & inibidores , Ataxina-3/genética , Ataxina-7/genética , Células Cultivadas , Relação Dose-Resposta a Droga , Fibroblastos/efeitos dos fármacos , Humanos , Estrutura Molecular , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/patologia , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/química , Proteínas Repressoras/genética , Relação Estrutura-AtividadeRESUMO
BACKGROUND: To establish an individualized surgical strategy for lymphadenectomy in ovarian cancer patients with the germline BRCA1 and BRCA2 pathogenic variants (BRCA1+ and BRCA2+), we investigated the clinicopathological characteristics that are involved in the increased risk of lymph node metastasis. METHODS: We retrospectively reviewed the data of Japanese women registered in the database of the Japanese Hereditary Breast and Ovarian Cancer Consortium, who underwent BRCA1 and BRCA2 genetic testing. RESULTS: We evaluated the predictors of lymph node metastasis in all patients with the information of age at the diagnosis, disease site, histological subtype, 2014 FIGO stage, personal breast cancer history and family history; 233, 153 and 32 patients in the BRCA- (no pathogenic variant), BRCA1+ and BRCA2+ groups, respectively. The prevalence of lymph node metastasis was not markedly different between BRCA- (20.0%), BRCA1+ (18.4%) and BRCA2+ (26.2%). Multivariate analysis revealed an absence of a family history of ovarian cancer as an independent predictor for an increased risk of lymph node metastasis in BRCA1+, and the prevalence of lymph node metastasis was 11.7 and 42.0% in the groups with and without a family history of ovarian cancer, respectively. This subgroup without a family history of ovarian cancer did not show any correlation with a particular variant of BRCA1, including two common variants of c.188 T > A and c.2800C > T. CONCLUSIONS: This study suggested that certain genetic factors related to the penetrance of hereditary breast and ovarian cancer syndrome altered the frequency of lymph node metastasis in BRCA1+ ovarian cancer, and family history may be useful to personalize the indication of lymphadenectomy.
Assuntos
Neoplasias das Tubas Uterinas/patologia , Síndrome Hereditária de Câncer de Mama e Ovário/patologia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias das Tubas Uterinas/genética , Feminino , Predisposição Genética para Doença , Síndrome Hereditária de Câncer de Mama e Ovário/genética , Humanos , Japão/epidemiologia , Metástase Linfática , Pessoa de Meia-Idade , Mutação , Neoplasias Ovarianas/genética , Penetrância , Neoplasias Peritoneais/genética , Estudos Retrospectivos , Fatores de RiscoRESUMO
The characteristic adverse events of olaparib, a PARP inhibitor, are nausea, vomiting, and anemia, and interstitial pneumonia is rarely reported. We report a case of interstitial pneumonia following the treatment of a metastatic breast cancer with olaparib. The patient was a 34-year-old woman. In March 2018, she was diagnosed with stage â £ breast cancer(multiple lung metastases). She was treated with epirubicin and cyclophosphamide followed by paclitaxel. In November 2018, brain and spinal cord metastases were detected, and she was treated with radiation. In December 2018, a BRCA1 deleterious mutation was confirmed, and treatment with olaparib was initiated. Six weeks later, olaparib was discontinued due to anemia; it also caused interstitial pneumonia. The interstitial pneumonia resolved following multidisciplinary treatment during hospitalization. Subsequently, she was treated with cyclophosphamide/methotrexate/fluorouracil. It is necessary to consider interstitial pneumonia as an adverse effect of olaparib.
Assuntos
Neoplasias da Mama , Doenças Pulmonares Intersticiais , Adulto , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Doenças Pulmonares Intersticiais/induzido quimicamente , Ftalazinas/efeitos adversos , Piperazinas/efeitos adversosRESUMO
We report the case of a 44-year-old male who underwent mastectomy plus axillary lymph node dissection after neoadjuvant chemotherapy for left breast cancer. During adjuvant therapy, multiple bone metastases and pericardial effusion were detected. Pericardial drainage was mandated for the patient, although no malignant cells were found. Despite the change in treatment, pericardial effusion worsened. Based on clinical findings, the patient was diagnosed with carcinomatous pericarditis and was switched to bevacizumab plus paclitaxel therapy. CT at 5 months showed improved pericardial effusion; treatment is ongoing.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama , Pericardite , Adulto , Bevacizumab , Neoplasias da Mama/tratamento farmacológico , Humanos , Masculino , Mastectomia , Recidiva Local de Neoplasia , Paclitaxel , Pericardite/etiologiaRESUMO
BACKGROUND: Expression of estrogen receptor α in breast cancer is essential for estrogen-dependent growth and partially determines the breast cancer subtype. In premenopausal women, expression of estrogen-regulated genes in estrogen receptor-positive breast cancer tissues are reportedly influenced by the menstrual cycle. METHODS: We investigated correlations between serum estradiol (E2; tested on the day of surgery) and expression of estrogen-regulated genes and proliferation genes in strongly estrogen receptor α-positive breast cancer tissues from 91 premenopausal women by quantitative reverse transcription-polymerase chain reaction. We also investigated correlations between serum progesterone levels on the day of surgery and mRNA expression of progesterone-regulated genes and proliferation genes. RESULTS: The serum E2 level affected expression of estrogen-regulated genes, including progesterone receptor (P = 0.016, Rs = 0.07) but showed no correlation with expression of genes associated with proliferation. We also observed strong positive correlations between mRNA expression of ESR1 and that of estrogen-regulated genes (P < 0.0001, Rs = 0.329-0.756) and proliferation genes (P < 0.0001, Rs = 0.753-0.843). The serum progesterone level affected expression of RANKL mRNA. However, we observed no correlations between serum progesterone and expression of Wnt-4 or proliferation genes. CONCLUSIONS: The serum E2 level on the day of surgery influences estrogen-regulated gene expression moderately in patients found to be strongly positive for estrogen receptor α by immunohistochemistry. Changes in serum E2 levels might influence the results of molecular profiling tests in premenopausal women with breast cancer.
Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Estrogênios/metabolismo , Expressão Gênica/genética , Progesterona/metabolismo , Adulto , Neoplasias da Mama/patologia , Feminino , Humanos , Pré-MenopausaRESUMO
BACKGROUND: We conducted an open-label, randomized controlled trial evaluating the appropriate treatment duration of leuprorelin acetate 3-month depot, TAP-144-SR (3M), administered postsurgically every 3 months for 2 years versus 3 or more (up to 5) years, in combination with tamoxifen, for 5 years in premenopausal endocrine-responsive breast cancer patients and reported similar survival benefit in the two treatment groups. We hereby present patient-reported quality of life (QOL) data obtained from this trial. METHODS: Three self-administered QOL questionnaires (QOL-ACD, QOL-ACD-B, FACT-ES subscale) were used, and the difference in QOL score changes between the two groups was analyzed using a mixed-effects model for repeated measures. RESULTS: Eligible patients (N = 222) were randomly assigned to a 2-year (2YG, N = 112) or 3-or-more-year treatment group (3YG, N = 110). The time courses of the three QOL scores during the trial period were similar in the two groups. The mean changes in the QOL scores from week 96 were largely stable through week 240 in the 3YG, but showed significantly greater improvement in the score changes from week 96 in the 2YG than the 3YG. Symptoms associated with menopause such as hot flashes and sweating contributed to these results. Menstruation recovery was associated with significantly greater improvement of these symptoms in the 2YG than the 3YG. CONCLUSIONS: Patient-reported menopause-associated symptoms and QOL improved after discontinuation of the LH-RH agonist administration and menstruation recovery. QOL information should be a consideration in long-term treatment.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante/métodos , Leuprolida/uso terapêutico , Qualidade de Vida/psicologia , Tamoxifeno/uso terapêutico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/patologia , Feminino , Humanos , Leuprolida/administração & dosagem , Leuprolida/farmacologia , Pessoa de Meia-Idade , Pré-Menopausa , Tamoxifeno/administração & dosagem , Tamoxifeno/farmacologia , Resultado do TratamentoRESUMO
PURPOSE: To assess the true conditions and perceptions of the personal lives of men and women working as surgeons in Japan. METHODS: In 2014, all e-mail subscribed members of the Japan Surgical Society (JSS, n = 29,861) were invited to complete a web-based survey. The questions covered demographic information, work environment, and personal life (including marital status, childcare, and nursing care for adult family members). RESULTS: In total, 6211 surgeons (5586 men and 625 women) returned the questionnaires, representing a response rate of 20.8%. Based on the questionnaire responses, surgeons generally prioritize work and spend most of their time at work, although women with children prioritize their family over work; men spend significantly fewer hours on domestic work/childcare than do their female counterparts (men 0.76 h/day vs. women 2.93 h/day, p < 0.01); and both men and women surgeons, regardless of their age or whether they have children, place more importance on the role of women in the family. CONCLUSIONS: The personal lives of Japanese surgeons differed significantly according to gender and whether they have children. The conservative idea that women should bear primary responsibility for the family still pertains for both men and women working as surgeons in Japan.
Assuntos
Família , Identidade de Gênero , Cirurgia Geral/organização & administração , Vida , Saúde Ocupacional , Médicas/psicologia , Sociedades Médicas/organização & administração , Cirurgiões/psicologia , Inquéritos e Questionários , Adulto , Idoso , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , TrabalhoRESUMO
PURPOSE: To assess the working styles of men and women working as surgeons in Japan. METHODS: In July, 2014, the Japan Surgical Society invited all their members (n = 29,861), through an internet campaign, to participate in a nationwide survey of surgeons. The items investigated in this descriptive study included demographic information and working styles, based on a questionnaire. RESULTS: In total, 6211 surgeons participated (response rate 20.8%, 5586 men and 625 women). The largest age stratum was 40-49 years for men and 30-39 years for women. Overall, respondents identified their labor contract, including salary and work hours, as the highest priority for improvement. Women with children were more likely to be part-time employees, work fewer hours, and take fewer house calls/on-calls than their male counterparts. Moreover, women of all ages earned a lower annual income than men, irrespective of whether they had children. Perception scores for discrimination related to work and promotion were significantly higher among women than men (p < 0.01 and p = 0.011, respectively). CONCLUSIONS: A significant difference in working style was observed between men and women working as surgeons in Japan.
Assuntos
Cirurgia Geral/organização & administração , Médicas/psicologia , Sociedades Médicas/organização & administração , Cirurgiões/psicologia , Inquéritos e Questionários , Trabalho , Adulto , Feminino , Humanos , Renda , Japão , Masculino , Pessoa de Meia-Idade , Admissão e Escalonamento de Pessoal , Médicas/economia , Salários e Benefícios , Sexismo , Cirurgiões/economiaRESUMO
Estrogen receptor(ER)-positive breast cancer accounts for approximately 80%of all breast cancers. The basic concept of endocrine therapy is to deplete estrogen(LH-RH agonist and aromatase inhibitor)and inhibit the action of estrogen against estrogen-dependent growth in ER-positive breast cancer. Recently, new molecular targeting agents, including an mTOR inhibitor and a CDK4/6 inhibitor, have been used in combination with endocrine therapy for the treatment of ER-positive metastatic breast cancer.
Assuntos
Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Cálcio , Estrogênios , Humanos , Terapia de Alvo Molecular , Receptores de EstrogênioRESUMO
Cell-penetrating peptides (CPP) have attracted many scientists' attention as intracellular delivery tools due to their high cargo molecule transportation efficiency and low cytotoxicity. Therefore, in many research fields CPP, such as HIV-Tat and oligoarginine (Rn), are used to deliver hydrophilic drugs and biomolecules, including proteins, DNA, and RNA. We designed four types of CPP that contained cationic α,α-disubstituted amino acids (ApiC2Gu and ApiC4Gu) as helical promoters; i.e., 1-4 [FAM-ß-Ala-(l-Arg-l-Arg-Xaa)3-(Gly)3-NH2 (1: Xaa=ApiC2Gu, 2: Xaa=ApiC4Gu), 3: FAM-ß-Ala-(l-Arg)8-ApiC2Gu-(Gly)3-NH2, and 4: FAM-ß-Ala-(l-Arg)5-ApiC2Gu-(l-Arg)2-ApiC2Gu-(Gly)3-NH2], and investigated their preferred secondary structures and cell membrane-penetrating ability. As a result, we found that the permeation efficiency of the CPP was affected by the number of helical promoters in their sequences. Specially, peptide 1, which contained three ApiC2Gu residues, formed a stable helical structure and passed through the cell membrane more efficiently than the other peptides. Moreover, it was demonstrated that the spatial arrangement of the peptides' side chains also influenced their permeability and the helical stabilization of their main chains.
Assuntos
Aminoácidos/química , Peptídeos Penetradores de Células/química , Animais , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Dicroísmo Circular , Humanos , Espectrometria de Massas , Microscopia Confocal , Conformação ProteicaRESUMO
OBJECTIVE: This study aimed to investigate the feasibility of an intervention program for women with breast cancer undergoing adjuvant anticancer therapy, and determine its preliminary effectiveness in reducing their unmet needs and psychological distress. METHODS: The intervention was based on the collaborative care model, and compromised four domains: identification of unmet needs, problem-solving therapy and behavioral activation supervised by a psychiatrist, psychoeducation and referral to relevant departments. Eligible women with breast cancer were provided the collaborative care intervention over four sessions. The feasibility of the program was evaluated by the percentage of women who entered the intervention and by the percentage of adherence to the program. Self-reported outcomes were measured by the Supportive Care Needs Survey-Short Form 34 (SCNS-SF34), the Profile of Mood States (POMS), the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), the Concern about Recurrence Scale, and pre- and post-intervention satisfaction with medical care. RESULTS: In total, 40 patients participated in this study. The rate of participation in the intervention was 68%, and the rate of adherence was 93%. Participants had significantly improved scores on total perceived needs, physical needs and psychological needs on the SCNS-SF34; vigor and confusion on the POMS and function (physical, emotional and cognitive), nausea and vomiting, dyspnea, appetite loss and financial difficulties on the EORTC QLQ-C30 compared with the baseline assessment. CONCLUSIONS: Our findings indicated the intervention program was feasible. Further study is needed to demonstrate the program's effectiveness in reducing unmet needs.