Synergistic effect of antagonists to KRas4B/PDE6 molecular complex in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis among all human cancers as it is highly resistant to chemotherapy. K-Ras mutations usually trigger the development and progression of PDAC. We hypothesized that compounds stabilizing the KRas4B/PDE6δ complex could serve as PDAC treatments. Using in silico approaches, we identified the small molecules C14 and P8 that reduced K-Ras activation in primary PDAC cells. Importantly, C14 and P8 significantly prevented tumor growth in patient-derived xenotransplants. Combined treatment with C14 and P8 strongly increased cytotoxicity in PDAC cell lines and primary cultures and showed strong synergistic antineoplastic effects in preclinical murine PDAC models that were superior to conventional therapeutics without causing side effects. Mechanistically, C14 and P8 reduced tumor growth by inhibiting AKT and ERK signaling downstream of K-RAS leading to apoptosis, specifically in PDAC cells. Thus, combined treatment with C14 and P8 may be a superior pharmaceutical strategy to improve the outcome of PDAC.

[Ovarian adenosarcoma with elevated CA125 antigen. Case report and literature review]. / Adenosarcoma de ovario asociado con elevación del antígeno sérico Ca-125. Informe de caso y revisión de literatura.

BACKGROUND: Adenosarcomas are rare tumors usually derived from the endometrium. About 50 cases of adenosarcomas of the ovary have been reported. The relationship between adenosarcoma and CA125 has not been described. The authors present a case of adenosarcoma with elevated CA125 because of the unusual presentation of this pathology and also because elevation of the CA125 antigen has not been reported in the literature. CLINICAL CASE: A 42-year-old woman presented for consultation for incidental right ovarian tumor and CA125 of 1100 U/mL. Histology revealed a homologous Müllerian adenosarcoma of the right ovary with sarcomatous overgrowth. CA125 decreased to 16 U/mL after surgery. Sixteen months post-surgery, the patient is disease free and with normal CA125. DISCUSSION: Ovarian adenosarcomas are more aggressive than adenosarcomas of the uterus. Because of the embryological origin, ovarian adenosarcomas are able to produce CA125 antigen, especially in the presence of sarcomatous overgrowth. With these facts, CA125 antigen may be useful as a prognostic factor because it may represent an indirect marker of sarcomatous overgrowth. CONCLUSIONS: CA125 may be useful for follow-up of ovarian adenosarcomas. Elevated CA125 antigen in adenosarcomas of the ovary may be indicative of sarcomatous overgrowth and poor prognosis.

[Molecular classification of breast cancer]. / Clasificación molecular del cáncer de mama.

Breast cancer is classified based on clinical stage, cellular morphology and immunohistochemical analysis. More precise prognostic factors are necessary to aid with therapeutic decisions. Breast cancer subtypes that differ in their genetic expression and prognosis have been determined using cDNA microarrays. These findings confirm the differences between the phenotypes and provide new knowledge about the biology of breast cancer. Based on the presence or absence of expression of the estrogen receptor (ER), breast cancer is divided in two groups: ER+ and ER-. Genetic expression profile has identified two subtypes of the ER+ tumors: luminal A and luminal B. ER- tumors also include two subtypes, the HER2+ and the basal type. These subtypes differ in their biology and both demonstrate short disease-free periods after treatment and poorer outcome. This classification has shown the relationship between cDNA microarrays and clinical outcome of these tumors. This classification is proposed as a method of identifying those patients who will demonstrate better results with the different adjuvant modalities.

Clasificación molecular del cáncer de mama / Molecular classification of breast cancer

Breast cancer is classified based on clinical stage, cellular morphology and immunohistochemical analysis. More precise prognostic factors are necessary to aid with therapeutic decisions. Breast cancer subtypes that differ in their genetic expression and prognosis have been determined using cDNA microarrays. These findings confirm the differences between the phenotypes and provide new knowledge about the biology of breast cancer. Based on the presence or absence of expression of the estrogen receptor (ER), breast cancer is divided in two groups: ER+ and ER-. Genetic expression profile has identified two subtypes of the ER+ tumors: luminal A and luminal B. ER- tumors also include two subtypes, the HER2+ and the basal type. These subtypes differ in their biology and both demonstrate short disease-free periods after treatment and poorer outcome. This classification has shown the relationship between cDNA microarrays and clinical outcome of these tumors. This classification is proposed as a method of identifying those patients who will demonstrate better results with the different adjuvant modalities.

Adenosarcoma de ovario asociado con elevación del antígeno sérico Ca-125: informe de caso y revisión de literatura / Ovarian adenosarcoma with elevated CA125 antigen: case report and literature review

BACKGROUND: Adenosarcomas are rare tumors usually derived from the endometrium. About 50 cases of adenosarcomas of the ovary have been reported. The relationship between adenosarcoma and CA125 has not been described. The authors present a case of adenosarcoma with elevated CA125 because of the unusual presentation of this pathology and also because elevation of the CA125 antigen has not been reported in the literature. CLINICAL CASE: A 42-year-old woman presented for consultation for incidental right ovarian tumor and CA125 of 1100 U/mL. Histology revealed a homologous Müllerian adenosarcoma of the right ovary with sarcomatous overgrowth. CA125 decreased to 16 U/mL after surgery. Sixteen months post-surgery, the patient is disease free and with normal CA125. DISCUSSION: Ovarian adenosarcomas are more aggressive than adenosarcomas of the uterus. Because of the embryological origin, ovarian adenosarcomas are able to produce CA125 antigen, especially in the presence of sarcomatous overgrowth. With these facts, CA125 antigen may be useful as a prognostic factor because it may represent an indirect marker of sarcomatous overgrowth. CONCLUSIONS: CA125 may be useful for follow-up of ovarian adenosarcomas. Elevated CA125 antigen in adenosarcomas of the ovary may be indicative of sarcomatous overgrowth and poor prognosis.

Factores pronósticos del carcinoma diferenciado de tiroides Hospital Dr. Roberto Calderón / Forecast factors of the differentiated carcinoma of thyroid Dr. Hospital Roberto Calderón R

Presenta estudio sobre el cancer diferenciado de tiroides (CDT). Se estudiaron un cohorte de 47 pacientes en 5 años (papilar, n=44; folicular, n=3) y una media de seguimeinto 2 años, para identificar los factores pronósticos y comparar el riesgo de recurrencia o muerte. La edad media fue de 43 años con una relación M: H 5:1. Se realizaron 80.9 porciento de tiroidectomias totales en los pacientes. De los diferentes factores pronósticos identificados tuvieron significancia: nivel de resolución quirúrgica del cirujano (p 0.009), tmaño del tumor primario (p 0.007), tipo histológico (p 0.0042), resección completa del tumo (p 0.012), metástasis a distancia (p 0.013), uso de 1 131 (p 0.017), supresión de TSH con levotiroxina (p 0.002) y radioterapia externa (p 0.031). Aplicando el sistema AMES se encontró que 32 porciento de los pacientes eran de alto riesgo y con los sitemas MACIS y EORTC solo el 23,4 porciento de estos, con diferencias significativas para cada grupo de riesgo en los diferentes sistemas (p 0.020, p 0.009 respectivamente). Basados en los factores pronósticos identificados y aplicando los sistemas (AMES, MACIS y EORTC), podemos seleccionar las estrategias de tratamiento y seguimiento oncológico