Exploring the role of GHRH antagonist MIA-602 in overcoming Doxorubicin-resistance in acute myeloid leukemia.

Acute myeloid leukemia (AML) is characterized by the rapid proliferation of mutagenic hematopoietic progenitors in the bone marrow. Conventional therapies include chemotherapy and bone marrow stem cell transplantation; however, they are often associated with poor prognosis. Notably, growth hormone-releasing hormone (GHRH) receptor antagonist MIA-602 has been shown to impede the growth of various human cancer cell lines, including AML. This investigation examined the impact of MIA-602 as monotherapy and in combination with Doxorubicin on three Doxorubicin-resistant AML cell lines, KG-1A, U-937, and K-562. The in vitro results revealed a significant reduction in cell viability for all treated wild-type cells. Doxorubicin-resistant clones were similarly susceptible to MIA-602 as the wild-type counterpart. Our in vivo experiment of xenografted nude mice with Doxorubicin-resistant K-562 revealed a reduction in tumor volume with MIA-602 treatment compared to control. Our study demonstrates that these three AML cell lines, and their Doxorubicin-resistant clones, are susceptible to GHRH antagonist MIA-602.

Age and Sex in the Development of Hepatic Encephalopathy: Role of Alcohol.

Hepatic encephalopathy (HE) is a neurological condition linked to liver failure. Acute HE (Type A) occurs with acute liver failure, while chronic HE (Type C) is tied to cirrhosis and portal hypertension. HE treatments lag due to gaps in understanding its development by gender and age. We studied how sex and age impact HE and its severity with combined liver toxins. Our findings indicate that drug-induced (thioacetamide, TAA) brain edema was more severe in aged males than in young males or young/aged female rats. However, adding alcohol (ethanol, EtOH) worsens TAA's brain edema in both young and aged females, with females experiencing a more severe effect than males. These patterns also apply to Type A HE induced by azoxymethane (AZO) in mice. Similarly, TAA-induced behavioral deficits in Type C HE were milder in young and aged females than in males. Conversely, EtOH and TAA in young/aged males led to severe brain edema and fatality without noticeable behavioral changes. TAA metabolism was slower in aged males than in young or middle-aged rats. When TAA-treated aged male rats received EtOH, there was a slow and sustained plasma level of thioacetamide sulfoxide (TASO). This suggests that with EtOH, TAA-induced HE is more severe in aged males. TAA metabolism was similar in young, middle-aged, and aged female rats. However, with EtOH, young and aged females experience more severe drug-induced HE as compared to middle-aged adult rats. These findings strongly suggest that gender and age play a role in the severity of HE development and that the presence of one or more liver toxins may aggravate the severity of the disease progression.

Antología de los primeros estudios clínicos con hormonas hipotalámicas: relato de una exitosa colaboración internacional / Anthology of the first clinical studies with hypothalamic hormones: a story of successful international cooperation

Our early pioneering clinical trials in Mexico with natural and synthetic thyrotropin-releasing hormone (TRH) and luteinizing hormone releasing hormone (LH-RH) also known as gonadotropin releasing hormone (Gn-RH), were reviewed. Highly purified TRH of porcine origin was shown to stimulate Thyrotropin (TSH) release in hypothyroid cretins. Subsequent tests with synthetic TRH also demonstrated significant increases in plasma TSH in normal men and women as well as in patients with primary hypothyroidism and other endocrine disorders. Even more extensive clinical studies were carried out with highly purified natural porcine LH-RH. Subjects with normal basal serum levels of gonadotropins, low levels (men and women pretreated with steroids) and high levels (e.g. post menopausal women) all responded to LH-RH with a release of LH and FSH. The results of these early studies with the natural LH-RH were confirmed by the use of synthetic LH-RH. These investigations made in Mexico with TRH and LH-RH preceded all other clinical studies by a wide margin. Subsequently various clinical investigations with LH-RH agonists and antagonists were also carried out. All these studies played a major role in introducing hypothalamic-releasing hormones into clinical medicine.

Desaparecimento radiológico de metástases pulmonares num paciente com carcinoma da próstata depois do tratamento com um LH-RH agonista / Radiological regression of lung metastasis in patient with carcinoma of the prostate after the treatment with LH-RH antaganist

Paciente com carcinoma de próstata, retençäo urinária, metástase pulmonar e metástase ósseas foi tratado com D-Trp-6-LH-RH (decapeptyl) por 11 meses. Após 4 meses, houve regressäo das metástases ósseas e pulmonares e alívio da obstruçäo urinária. Apesar desse tratamento ter sido interrompido há mais de 18 meses, o paciente continua assintomático e sem recorrência das metástases ósseas e pulmonares

Acción inhibitoria selectiva del análogo D5-F-TrP8-D-Cys14 somatostatina sobre la liberación de insulina, hormona del crecimiento y glucagon, inducida con arginina en individuos normales / Selective inhibitory effect of the analog D5-F-TrP8-D-Cys14 somatostatin on the arginine induced release of insulin, growth hormone and glucagon, in normal human beings

Se estudió en un grupo de individuos normales la acción de varias dosis de somatostatina y del análogo D5-F-TrP8-D-Cys14-SS sobre la liberación inducida por arginina de insulina, glucagon y hormona de crecimiento (HC). La somatostatina en dosis de 100 g/h suprimió la liberación de insulina, glucagon y HC. El análogo D5-F-TrP8-D-Cys14-SS en dosis de 10 a 20 g/h inhibió a la HC y al glucagon, pero no a la insulina. Estos resultados muestran que es posible obtener análogos de la somatostatina que supriman en forma selectiva a la liberación de insulina, lo que puede ser de gran valor clínico en el manejo de diabetes mellitus, acromegalia, pancreatitis y úlcera péptica

Regulacion peptidergica del apetito. / Peptidergic appetite regulation

La funcion del hipotalamo en la regulacion del apetito se basa en el conocimiento de areas especificas cuya estimulacion o destruccion produce efectos definidos de hiperfagia o de afagia, pero hasta el momento no se ha identificado el mecanismo. Desde hace mas de 15 anos se postulo que la regulacion del apetito podria efectuarse por un mecanismo humoral, mas que neurogeno, y que la substancia causante podria ser elaborada por el hipotalamo. Este enunciado se apoya con la identificacion de varias de las hormonas tipicamente gastrointestinales, que tambien se encuentran en tejido nervioso central, especialmente en hipotalamo, en donde pueden participar en la regulacion del apetito. Recientemente se ha encontrado que tienen tambien efecto en la regulacion del apetito otros peptidos no relacionados con el tubo gastrointestinal.Describimos algunos de los hallazgos mas importantes que apoyan la participacion peptidergica a nivel hipotalamico en el complejo de la regulacion del apetito