[Can we manage the dying process? Advance directives].
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Advance Directives↗
Biomedical subjects
Jaime Sanz-Ortiz
Publications and source records attributed to Jaime Sanz-Ortiz.
Informed consent and sedation.
The concept of autonomy was not included in the Hippocratic Oath. Nowadays the principle of respect for autonomy is an important right. The basic paradigm of autonomy in health-care, politics and other contexts is expressed as informed consent. In the palliative-care setting, there can be some difficulties in getting informed consent, especially at the end-of-life stage. Can it be good for the patient, always? Could there be some exceptions? At the time of agonizing pain, getting informed consent could become an additional burden for the patient. This present article attempts to shed light on this issue. In our experience, it is not necessary to obtain written consent for a patient who has already expressed his priorities in advance. We believe that this is a good stance for patients as well as doctors.
Advance Directives↗
Breast cancer cells can evade apoptosis-mediated selective killing by a novel small molecule inhibitor of Bcl-2.
Proteins of the Bcl-2 family are key regulators of caspase activation and apoptosis. Some members of this family, notably Bcl-2 and Bcl-x(L), are overexpressed in cancer cells, which have been associated with chemoresistance. We have designed and synthesized a small molecule inhibitor of Bcl-2, named YC137, and studied its role in cancer cells. In vitro studies showed that YC137 inhibits the binding of the Bid BH3 peptide to Bcl-2, thus disrupting an interaction essential for the antiapoptotic activity of Bcl-2. This inhibitor induces apoptosis of hematopoietic progenitors overexpressing Bcl-2 but not Bcl-x(L) and breast cancer cells that express high levels of Bcl-2. On the contrary, a variety of normal primary cells, including CD34(+) progenitors, myoblasts, and peripheral blood mononuclear cells, do not respond to the inhibitor. A breast cancer cell line resistant to YC137 was generated. Analysis of resistant cells revealed a reduced expression of Bcl-2, which correlated with low activation of signal transducer and activator of transcription-3 (Stat3) and reduced expression of the human epidermal growth factor receptor-2 (HER2). Of note, YC137-resistant cells were more sensitive to apoptosis induced by chemotherapy. Because HER2 has not been linked previously to the Stat3-Bcl-2 transcriptional pathway, we additionally confirmed that specific blockade of HER2 in breast cancer cells resulted in down-regulation of Stat3 activity and reduced levels of Bcl-2. Consistently, HER2 blockade led to YC137 resistance. These data provide evidence for the selective killing of tumor cells by YC137 and represent the first example of in vitro selection of cancer cells refractory to a Bcl-2 inhibitor.
Apoptosis↗
Long-term results of a phase II trial of induction chemotherapy with uracil-ftegafur (UFT), vinorelbine, and cisplatin (UFTVP) followed by radiotherapy concomitant with UFT and carboplatin (RT/UFTJ) in a primary site preservation setting for resectable locally advanced squamous cell carcinoma of larynx and hypopharynx.
OBJECTIVE: We present long-term results of a phase II trial of induction chemotherapy (IC) with uracilftegafur (UFT) 200 mg/m orally days 1 to 21, vinorelbine 25 mg/m intravenously (IV) days 1 and 8, and cisplatin 100 mg/m IV day 1 (UFTVP) each for 21 days for 4 courses, followed by radiotherapy concomitant with UFT 100 mg/m orally daily and carboplatin (area under the curve [AUC] = 0.5 IV weekly) (RT/ UFTJ), without surgery to the primary site if response, in patients (pts) with resectable locally advanced squamous cell carcinoma of the larynx and hypopharynx. The primary endpoint was clinical complete response (CR) to induction UFTVP, and secondary endpoints were long-term overall survival (OS) and survival with primary site preservation (SPP). RESULTS: Between 1994 and 1997, 37 pts were included. CR to IC was 54% (95% confidence interval [CI] 43-65%). Main toxicity of UFTVP was G 3,4 neutropenia (73% of pts, 16% developed febrile neutropenia). After IC, primary site was treated with RT in 29 pts: 20 of them received RT/UFTJ (main toxicity mucositis G 3,4 70%). No pt died during treatment. Actuarial 5-year OS and SPP were 57% and 37%, respectively. CONCLUSIONS: This approach has significant activity and acceptable toxicity for achieving promising long-term OS and SPP and deserves further investigation.
Adult↗