RESUMO
Acute tissue injury causes DNA damage and repair processes involving increased cell mitosis and polyploidization, leading to cell function alterations that may potentially drive cancer development. Here, we show that acute kidney injury (AKI) increased the risk for papillary renal cell carcinoma (pRCC) development and tumor relapse in humans as confirmed by data collected from several single-center and multicentric studies. Lineage tracing of tubular epithelial cells (TECs) after AKI induction and long-term follow-up in mice showed time-dependent onset of clonal papillary tumors in an adenoma-carcinoma sequence. Among AKI-related pathways, NOTCH1 overexpression in human pRCC associated with worse outcome and was specific for type 2 pRCC. Mice overexpressing NOTCH1 in TECs developed papillary adenomas and type 2 pRCCs, and AKI accelerated this process. Lineage tracing in mice identified single renal progenitors as the cell of origin of papillary tumors. Single-cell RNA sequencing showed that human renal progenitor transcriptome showed similarities to PT1, the putative cell of origin of human pRCC. Furthermore, NOTCH1 overexpression in cultured human renal progenitor cells induced tumor-like 3D growth. Thus, AKI can drive tumorigenesis from local tissue progenitor cells. In particular, we find that AKI promotes the development of pRCC from single progenitors through a classical adenoma-carcinoma sequence.
Assuntos
Injúria Renal Aguda , Adenoma , Carcinoma de Células Renais , Neoplasias Renais , Adenoma/genética , Animais , Biomarcadores Tumorais , Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Camundongos , Recidiva Local de Neoplasia , Células-TroncoRESUMO
INTRODUCTION: We present a case of a spongiosus-cutaneous fistula in a 39-year-old man with recurrent episodes of cutaneous abscess in dorsal middle third penis (5 × 3 cm) treated with Hyperbaric Oxygen Therapy (HBOT). CASE REPORT: After emptying nodular abscess, the patient was noncompliant for further surgery. Therefore, it was suggested the association between HBOT and antibiotic therapy. HBOT is carried out in a hyperbaric room, where the internal pressure is increased (compression phase) by entering compressed air up to 283.71 kPa in about 10 minutes. Every HBOT cycle lasted 24 days in which the patient had been taking Amoxicillin/Clavulanic Acid 875 mg/125 mg 3 tabs/day and Sulfamethoxazole/Trimethoprim 160 mg/800 mg 2 tabs/day for 2 weeks. At the end of the treatment, a penile magnetic resonance imaging and an ultrasonography were executed and they evidenced a complete remission of the lesion. In the subsequent 22 months, there was no recurrence. CONCLUSIONS: Our results suggest that HBOT is an effective treatment for chronic wounds, including a spongiosus-cutaneous fistula of unknown cause, when used in combination with conventional standard therapy or further interventions. At present time, the gold standard remains surgery; nevertheless, our experience with HBOT may stimulate its use in clinical trials.
Assuntos
Abscesso/complicações , Fístula Cutânea/etiologia , Fístula Cutânea/terapia , Oxigenoterapia Hiperbárica , Pênis , Abscesso/microbiologia , Adulto , Fístula Cutânea/microbiologia , Fístula Cutânea/patologia , Humanos , Oxigenoterapia Hiperbárica/métodos , Masculino , Pênis/microbiologia , Resultado do Tratamento , CicatrizaçãoRESUMO
INTRODUCTION: We present a case of a spongiosus-cutaneous fistula in a 39-year-old man with recurrent episodes of cutaneous abscess in dorsal middle third penis (5 × 3 cm) treated with Hyperbaric Oxygen Therapy (HBOT). CASE REPORT: After emptying nodular abscess, the patient was noncompliant for further surgery. Therefore, it was suggested the association between HBOT and antibiotic therapy. HBOT is carried out in a hyperbaric room, where the internal pressure is increased (compression phase) by entering compressed air up to 283.71 kPa in about 10 minutes. Every HBOT cycle lasted 24 days in which the patient had been taking Amoxicillin/Clavulanic Acid 875 mg/125 mg 3 tabs/day and Sulfamethoxazole/Trimethoprim 160 mg/800 mg 2 tabs/day for 2 weeks. At the end of the treatment, a penile magnetic resonance imaging and an ultrasonography were executed and they evidenced a complete remission of the lesion. In the subsequent 22 months, there was no recurrence. CONCLUSIONS: Our results suggest that HBOT is an effective treatment for chronic wounds, including a spongiosus-cutaneous fistula of unknown cause, when used in combination with conventional standard therapy or further interventions. At present time, the gold standard remains surgery; nevertheless, our experience with HBOT may stimulate its use in clinical trials.
