ABSTRACT
Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of nonsmall-cell lung cancer (NSCLC). It carries a poor prognosis, even among other subtypes of NSCLC. Currently, most treatment strategies for PSC are derived from regimens aimed at managing soft tissue sarcomas or NSCLC. The use of doxorubicin plus ifosfamide and pemetrexed has been well established in the management of soft tissue carcinoma and other nonsmall-cell lung cancers, respectively. We report the case of a 69-year-old male diagnosed with PSC who was managed with doxorubicin plus ifosfamide and pemetrexed therapy. Our patient initially responded to the therapy but had rapid progression and died 8 months after the initiation of treatment. Upon genetic analysis, it was revealed the patient had overexpression of the MDM2 protein, which has been associated with poor response to therapy. This case highlights the need for a personalized treatment approach, as well as the need for a standardized treatment regimen for managing PSC.
ABSTRACT
Patients with triple-negative breast cancer (TNBC) have a poor prognosis, partly because of the absence of targeted therapies. Recognition of the key role of immune responses against cancer has allowed the advent of immunotherapy, focused on the inhibition of negative immune checkpoints, such as CTLA-4. CTLA-4 is also expressed in some cancer cells, but its activity in tumor cells is not completely understood. Thus, the aim of the present work was to determine the biological landscape and functions of CTLA-4 expressed in TNBC cells through preclinical and in silico analysis. Exploration of CTLA-4 by immunohistochemistry in 50 TNBC tumors revealed membrane and cytoplasmic expression at different intensities. Preclinical experiments, using TNBC cell lines, showed that stimulation of CTLA-4 with CD80 enhances activation of the ERK1/2 signaling pathway, while CTLA-4 blockade by Ipilimumab induces the activation of AKT and reduces cell proliferation in vitro. We then developed an analytic pipeline to define the effects of CTLA-4 in available public data that allowed us to identify four distinct tumor clusters associated with CTLA-4 activation, which are characterized by enrichment of distinctive pathways associated with cell adhesion, MAPK signaling, TGF-ß, VEGF, TNF-α, drug metabolism, ion and amino acid transport, and KRAS signaling, among others. In addition, blockade of CTLA-4 induced increased secretion of IL-2 by tumor cells, suggesting that the receptor regulates cellular functions that may impact the immune microenvironment. This is relevant because a deep characterization of immune infiltrate, conducted using public data to estimate the abundancies of immune-cell types, showed that CTLA-4-activated-like tumors present a conditional immune state similar to an escape phenotype exploited by cancer cells. Finally, by interrogating transcriptional predictors of immunotherapy response, we defined that CTLA-4 activation correlates with high immune scores related to good clinical predicted responses to anti-CTLA-4 therapy. This work sheds new light on the roles of activated CLTA-4 in the tumor compartment and suggests an important interplay between tumor CLTA-4-activated portraits and immune-infiltrating cell populations.
ABSTRACT
El cáncer de próstata se erige como uno de los tumores sólidos mas frecuentes a nivel mundial, habiendo alcanzado el primer lugar en Europa con una incidencia de 214 casos por cada 1000 hombres, superando así al cáncer de pulmón y colorrectal. En Chile, el cáncer de próstata es el segundo cáncer que produce más muertes en hombres, siendo superado sólo por el cáncer de estomago, con una tasa ajustada de 17,82 cada 100.000 hombres. El descubrimiento y utilización de marcadores tumorales en medicina ha afectado de manera positiva la detección temprana, diagnóstico, etapificación y seguimiento de variadas enfermedades malignas, entre ellas el antígeno prostático específico (PSA) en cáncer de próstata. Material y método: Todos los hombres mayores de 45 años atendidos en el Hospital DIPRECA y el HOSCAR entre enero del 2009 y Junio del 2011, sin una historia previa de cáncer prostático y cumpliendo con los criterios de sospecha para cáncer de próstata y para la realización de una biopsia prostática fueron incluidos en el estudio. De una muestra de sangre venosa tomada previo a la realización de la biopsia prostática se realiza la detección de células prostáticas en sangre mediante doble inmunomarcación con anticuerpos monoclonales anti APE y CD45.El estudio fue realizado de manera ciega para los procesadores de ambas muestras (CPCs y Biopsia prostática), prospectivo, con consentimiento informado y aprobación por parte del comité de ética local. Resultados: En el total de los pacientes incluidos en el estudio, al utilizar un nivel de corte de PSA para detección de cáncer de próstata mayor a 4ng/ml, el PSA muestra una sensibilidad de un 91 por ciento (IC 95 por ciento; 0,84-0,98) y una especificidad de un 25 por ciento (IC95por ciento; 0,17-0,3), con un cuociente de probabilidad positivo de 1,22 (IC 95 por ciento; 1,06-1,33) y un cuociente de probabilidad negativode 0,34 (IC 95 por ciento; 0,17-0,87). Valor predictivo positivo de 0,32 (IC 95 por ciento; 0,25-0,39)...
Prostate cancer has become one of the most frequently solid tumors worldwide, reaching the first place in Europe with an occurrence of 214 cases for every 1000 men, surpassing lung and colon cancer. In Chile, prostate cancer is the cancer with the second highest level of deaths in men, only being surpassed by stomach cancer, with an adjusted rate of 17.82 in every 100,000 men The discovery and use of tumoral markers in medicine has positively affected the early detection, diagnosis, staging and follow-up of varied malignant illnesses, among those, the prostatic specific antigen (PSA) in prostate cancer. Material and method: All men over 45 who were seen in DIPRECA and HOSCAR Hospitals between January 2009 and June 2011, without a previous history of prostate cancer, and who meet the suspicion criteria for prostate cancer and to make a prostatic biopsy, were included in the study. From a venous blood sample taken before the prostatic biopsy, the detection of prostatic cells in blood was done using double immunomarking with monoclonal anti-APR antibodies and CD45. The study was done blindly for the processes of both samples (CPCs and Prostatic biopsy), prospectively, with the informed consent and approval of the local ethics committee. Results: From the total number of patients included in the study, upon using a cutoff level of the PSA to detect prostate cancer above 4ng/ml, the PSA shows a sensitivity of 91 percent (IC 95 percent; 0.84-0.98) and a specificity of 25 percent (IC 95 percent; 0.17-0.3), with a positive probability quotient of 1.22 (IC 95 percent; 106-1.33) and a negative probability quotient of 0.34 (IC 95 percent; 0.17-0.87).Positive predictive value of 0.32 (IC 95 percent; 0.25-0.39) and a negative predictive value of 87percent (IC 95 percent; 0.77-0.97). The area under the ROC curve for the PSA as a prostate cancer detection mechanism was 0.788.Upon analyzing the CPCs as a diagnostic test for prostate cancer in this same group of...
Subject(s)
Humans , Male , Middle Aged , ROC Curve , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/blood , Prostate-Specific Antigen/blood , /blood , Prospective Studies , False Positive Reactions , Sensitivity and Specificity , Mass Screening , Predictive Value of TestsABSTRACT
El cáncer de próstata se erige como uno de los tumores sólidos mas frecuentes a nivel mundial, habiendo alcanzado el primer lugar en Europa con una incidencia de 214 casos por cada 1000 hombres, superando así al cáncer de pulmón y colorrectal. En Chile, el cáncer de próstata es el segundo cáncer que produce mas muertes en hombres, siendo superado sólo por el cáncer de estomago, con una tasa ajustada de 17,82 cada 100.000 hombres. El descubrimiento y utilización de marcadores tumorales en medicina ha afectado de manera positiva la detección temprana, diagnóstico, etapificación y seguimiento de variadas enfermedades malignas, entre ellas el antígeno prostático específico (PSA) en cáncer de próstata. Todos los hombres mayores de 45 años atendidos en el Hospital DIPRECA y el HOSCAR entre enero del 2009 y Junio del 2011, sin una historia previa de cáncer prostático y cumpliendo con los criterios de sospecha para cáncer de próstata y para la realización de una biopsia prostática fueron incluidos en el estudio. De una muestra de sangre venosa tomada previo a la realización de la biopsia prostática se realiza la detección de células prostáticas en sangre mediante doble inmunomarcación con anticuerpos monoclonales anti APE y CD45.El estudio fue realizado de manera ciega para los procesadores de ambas muestras (CPCs y Biopsia prostática), prospectivo, con consentimiento informado y aprobación por parte del comité de ética local...
Prostate cancer stands as one of the most common solid tumors worldwide, having achieved the first place in Europe with an incidence of 214 cases per 1000 men, surpassing lung cancer and colorectal cancer In Chile, prostate cancer is the second cancer causing deaths in men, surpassed only by gastric cancer, with an adjusted rate of 17.82 per 100,000 men. The discovery and use of tumor markers in medicine has positively affected early detection, diagnosis, staging and follow up of various malignancies, including prostate-specific antigen (PSA) in prostate cancer. All men over 45 years consulting at DIPRECA and HOSCAR Hospitals between January 2009 and June 2011, without a prior history of prostate cancer and fulfilling criteria to perform of a prostate biopsy were included in the study. To detect prostate cells in blood a venous blood sample taken prior to prostate biopsy and a double immunostaining with monoclonal antibodies against PSA and CD45 is performed. The study was blind to the processors of both samples (CPCs and prostate biopsy), and it was prospective, with informed consent and approval by the local ethics committee...