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1.
Cancer Res Commun ; 3(9): 1756-1769, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37674528

RESUMO

Mechanisms for Helicobacter pylori (Hp)-driven stomach cancer are not fully understood. In a transgenic mouse model of gastric preneoplasia, concomitant Hp infection and induction of constitutively active KRAS (Hp+KRAS+) alters metaplasia phenotypes and elicits greater inflammation than either perturbation alone. Gastric single-cell RNA sequencing showed that Hp+KRAS+ mice had a large population of metaplastic pit cells that expressed the intestinal mucin Muc4 and the growth factor amphiregulin. Flow cytometry and IHC-based immune profiling revealed that metaplastic pit cells were associated with macrophage and T-cell inflammation. Accordingly, expansion of metaplastic pit cells was prevented by gastric immunosuppression and reversed by antibiotic eradication of Hp. Finally, MUC4 expression was significantly associated with proliferation in human gastric cancer samples. These studies identify an Hp-associated metaplastic pit cell lineage, also found in human gastric cancer tissues, whose expansion is driven by Hp-dependent inflammation. Significance: Using a mouse model, we have delineated metaplastic pit cells as a precancerous cell type whose expansion requires Hp-driven inflammation. In humans, metaplastic pit cells show enhanced proliferation as well as enrichment in precancer and early cancer tissues, highlighting an early step in the gastric metaplasia to cancer cascade.


Assuntos
Helicobacter pylori , Neoplasias Gástricas , Humanos , Animais , Camundongos , Proteínas Proto-Oncogênicas p21(ras) , Modelos Animais de Doenças , Inflamação
2.
Palliat Support Care ; 14(6): 680-685, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27215292

RESUMO

OBJECTIVE: The goal of this pilot study was to identify the processes by which healing occurs in patients who experience a life-threatening illness. METHOD: Healing was examined by using two qualitative studies that employed a semistructured interview process (interviews lasted between 30 and 115 minutes). There were 10 cardiac event survivors and 9 cancer survivors. These participants came from a community hospital setting (cardiac), nonmedical holistic services organization (cancer), and a research hospital (cancer). Before participants could take part in the study, they were administered preliminary screening measurements, the first of which was an instrument similar to the Distress Thermometer. Participants then self-reported their positive life-transforming changes. If one to three changes were reported six months after onset of the illness, participants were deemed to have passed the screening. Finally, participants were tested for speaking volume and clarity. RESULTS: An overall theme that was prevalent throughout the interviews was medical support. Participants found that their positive, life-transforming changes were typically connected with supportive caregivers who helped to create a culture of care. They also indicated that an absence of this medical supportive care hindered development of such life-transforming changes. SIGNIFICANCE OF RESULTS: Our results indicate that a medical care team will be more effective if a positive culture of care is created. This can be implemented if the team provides comfort, which involves being more engaged in the treatment of patients as well as being more attentive to their psychosocial needs.


Assuntos
Cuidadores/psicologia , Neoplasias/psicologia , Apoio Social , Sobreviventes/psicologia , Assistência Terminal/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Projetos Piloto , Pesquisa Qualitativa , Assistência Terminal/psicologia , Assistência Terminal/normas
3.
Palliat Support Care ; 13(3): 653-60, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24774033

RESUMO

OBJECTIVE: Individuals with life-threatening illness often engage in some form of spirituality to meet increased needs for meaning and purpose. This study aimed to identify the role of spirituality in persons who had reported positive, life-transforming change in relation to life-threatening cancer or cardiac events, and to connect these roles to palliative and supportive care. METHOD: A purposive sample of 10 cardiac survivors and 9 cancer survivors was recruited. Once the participants had given informed consent and passed screening in relation to life-transforming change and distress, they engaged in a semistructured one-hour qualitative interview on the theme of how their life-transforming change occurred in the context of their life-threatening illness. In the present article, our phenomenological analysis focuses on participants' references to purpose and meaning in their lives, with particular attention to the role and context of participants' spirituality. RESULTS: Participants mentioned spirituality, meaning, and purpose in many contexts, including connecting with family and friends, nature, art, music, and sometimes creating a relationship with God. Participants often accessed spirituality by enhancing connections in their own lives: with a higher power, people, their work, or themselves. These enhanced connections gave participants greater meaning and purpose in their lives, and substantially helped participants to adjust to their life-threatening illnesses. SIGNIFICANCE OF RESULTS: Understanding the roles and contexts of spirituality among patients with a life-threatening illness allows us to develop better palliative and supportive care plans. Spiritually oriented supportive care may include support groups, yoga, meditation, nature, music, prayer, or referral to spiritual or religious counselors. A quantitative scale is needed to help healthcare clinicians assess the spiritual and coping needs of individuals with life-threatening illness.


Assuntos
Climatério/psicologia , Acontecimentos que Mudam a Vida , Cuidados Paliativos/psicologia , Espiritualidade , Sobreviventes/psicologia , Adaptação Psicológica , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa
4.
Palliat Support Care ; 13(3): 749-56, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24892820

RESUMO

OBJECTIVE: One of the most prevalent life-threatening illnesses is heart disease. The initial trauma of being diagnosed with a life-threatening illness or having a cardiac event can begin a psychosocial chain reaction that results in a transformation of the lives of these patients. The goal of our study was to investigate the lived experiences of psychosocial healing in rehabilitation of cardiac patients using a qualitative written interview. METHOD: A purposive sample of 14 cardiac event survivors was recruited. Participants were interviewed after informed consent and screening. We used a qualitative analysis and model-revision approach similar to the procedure outlined by Charmaz (2006). RESULTS: Participants consistently mentioned that a heightened awareness of mortality was a motivating factor that led to participants focusing more on their family and relationships, having an enhanced outlook on life, and making healthy lifestyle changes. SIGNIFICANCE OF RESULTS: If clinicians are able to employ a measure to better understand the nature of a patient's progression from cardiac event to successful recovery, interventions such as cardiac rehabilitation can be implemented earlier and more effectively during the course of the illness and recovery phases of treatment. Theoretically, this early detection of a patient's progression could reduce the time spent recovering from a cardiac event, and it would allow treatments for these conditions to better alleviate the psychosocial concerns faced by patients.


Assuntos
Atitude Frente a Morte , Cardiopatias/psicologia , Psicologia , Sobreviventes/psicologia , Idoso , Feminino , Cardiopatias/reabilitação , Humanos , Masculino , Pesquisa Qualitativa
5.
Cases J ; 2: 6376, 2009 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-19829797

RESUMO

Fungal infections of the central nervous system are an uncommon cause of rapid decline in consciousness. We describe the case of central nervous system aspergillosis in a patient on immunosupressants whose clinical course highlights the need for an aggressive approach to diagnosis.

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