Neoadjuvant chemotherapy with dose-dense MVAC in muscle-invasive bladder cancer: a tertiary center experience

Purpose Neoadjuvant chemotherapy in muscle-invasive bladder cancer (MIBC) patients has proven beneficial in overall survival. However, the optimal regimen is still a matter of debate. Materials and method In this retrospective analysis, we evaluate the results obtained in 42 patients treated in our center with 4 cycles of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) followed by radical cystectomy from August 2015 to October 2020. All patients had cT2 or higher non-metastatic MIBC. Clinical and pathological outcomes are reported. Results Of the 42 patients, 90.5% were men (n = 38) and the mean age was 65 years. All of them had ECOG 0–1 at diagnosis and most tumors had an initial clinical stage T2N0 (76%). Thirty-six patients (85.7%) completed 4 cycles of neoadjuvant treatment, and 21.4% required a dose reduction. The most frequent adverse event (AE) was grade 1–2 asthenia (81%), while neutropenia was the most frequent grade 3 or higher AE (38%). Complete pathological response (ypT0, ypN0) was achieved in 50% of patients (n = 21), and down-staging was observed in 57.1% (n = 24). Only one patient presented radiological progressive disease during neoadjuvant treatment (2.4%), and after a mean follow-up time of 31.5 months, 33.3% of patients experienced disease recurrence. Conclusions Neoadjuvant chemotherapy with 4 cycles of dd-MVAC is an effective regimen with high rates of pathological complete responses and down-staging along with an acceptable toxicity profile. DD-MVAC should be considered as an alternative to cisplatin and gemcitabine in patients with good clinical performance status (AU)

The synergistic anticancer effect of CBD and DOX in osteosarcoma

Background Osteosarcoma is a malignant tumor that can present with pain in the bones, joints, and local masses. The incidence is highest in adolescents, and the most common sites are the distal femur, proximal tibia and proximal humerus metaphyseal. Doxorubicin is the first-line chemotherapeutic agent for the treatment of osteosarcoma, but it has many side effects. Cannabidiol is a non-psychoactive plant cannabinoid cannabinol (CBD) that has been shown to be effective against osteosarcoma; however, the molecular targets and mechanisms of CBD action in osteosarcoma remain unclear. Methods Cell proliferation, migration, invasion and colony formation were analyzed using two drugs alone or in combination to evaluate their inhibitory effects on the malignant characteristics of OS cells. Apoptosis and the cell cycle were detected by flow cytometry. The synergistic inhibitory effect of doxorubicin/cannabidiol on tumors was also detected in nude mouse xenotransplantation models. Results Through analysis of two osteosarcoma cell lines, MG63 and U2R, it was found that the cannabidiol/doxorubicin combination treatment synergistically inhibited growth, migration and invasion and induced apoptosis, blocking G2 stagnation in OS cells. Further mechanistic exploration suggests that the PI3K-AKT-mTOR pathway and MAPK pathway play an important role in the synergistic inhibitory effect of the two drugs in osteosarcoma. Finally, in vivo experimental results showed that the cannabidiol/doxorubicin combination treatment significantly reduced the number of tumor xenografts compared to cannabidiol alone or doxorubicin alone. Conclusions Our findings in this study suggest that cannabidiol and doxorubicin have a synergistic anticancer effect on OS cells, and their combined application may be a promising treatment strategy for OS (AU)

Long-time follow-up of patients with untreated peripheral T cell lymphoma following chidamide combined with cyclophosphamide, epirubicin, vindesine, prednisone, and etoposide therapy: a single-center propensity score-matching study

Purpose This is a retrospective, single-center PSM study evaluating the efficacy and safety of chidamide combined with the CHOEP (C-CHOEP) regimen versus the single CHOEP regimen in patients with untreated peripheral T cell lymphomas (PTCL). Patients Patients newly diagnosed with PTCL between January 2015 and June 2021 were recruited, and were 1:1 divided into C-CHOEP and CHOEP groups according to their first-line chemotherapy regimens. The PSM method was used to match the baseline variables to balance the confounding factors. Results A cohort of 33 patients each in the C-CHOEP and CHOEP groups was generated after propensity score-matching (PSM). The complete remission (CR) rates of the C-CHOEP regimen were higher than that of the CHOEP regimen (56.3 vs. 25.8%, p = 0.014), whereas the duration of response of the C-CHOEP group was shorter (median DOR 30 vs. 57 months), resulting in roughly similar progression-free survival (PFS) and (overall survival) OS between the two groups. The responding patients who received chidamide maintenance therapy showed a trend of superior PFS and OS compared with patients who did not receive maintenance therapy. Conclusions The C-CHOEP regimen was well tolerated but failed to show advantages over the CHOEP regimen in patients with untreated PTCL; however, the chidamide maintenance may contribute to a more durable response and stable long-term survival (AU)

Evaluación de una vena periférica para quimioterapia intravenosa: un estudio prospectivo observacional / Evaluation of a peripheral vein for intravenous chemotherapy: a prospective observational study

Este estudio tuvo como objetivo evaluar las alteraciones en el tiempo de una vena periférica utilizada para la infusión de quimioterapia en pacientes con cáncer de mama. Es un estudio observacional prospectivo que incluyó pacientes que estaban programados para recibir infusión periférica de quimioterapia. A estos pacientes se les evaluó la primera vena periférica utilizada para la infusión en cinco momentos: antes de la venopunción, después de la extracción del dispositivo al final de la primera infusión de quimioterapia y los días 21, 42 y 63 después de la primera infusión. El resultado primario fue el calibre de la vena, medido en milímetros con un transiluminador Veinlite LEDX® y una cinta métrica. Se inscribieron en el estudio 59 mujeres que recibieron doxorrubicina y docetaxel por primera vez. El tamaño del calibre varió de 2 a 4 milímetros en la línea de base y disminuyó con el tiempo. Durante el período de seguimiento, las venas periféricas de 35 mujeres (59,3%) se midieron a 0 mm el día 63. Las 24 mujeres restantes (40,7%) tuvieron cierta recuperación, pero para 15 de ellas (62,5%) la vena se convirtió en un cordón palpable. La viabilidad de utilizar una vena periférica para realizar quimioterapia disminuyó a medida que avanzaba el tratamiento.(AU)

This study aimed to assess over time alterations of a peripheral vein used for chemotherapy infusion in patients with breast cancer. It is a prospective observational study which included patients who were scheduled to receive peripheral infusion of chemotherapy. These patients had the first peripheral vein used for infusion evaluated in five moments: before the venipuncture, after device removal at the end of the first chemotherapy infusion, and on days 21, 42, and 63 after the first infusion. The primary outcome was the caliber of the vein, measured in millimeters with a Veinlite LEDX® transilluminator and a tape measure. Fifty-nine women receiving doxorubicin and docetaxel for the first time were enrolled to the study. The caliber size varied from 2 to 4 millimeters at baseline, and decreased overtime. During the follow-up period, peripheral veins of 35 women (59.3%) were measured at 0 mm at day 63. The remaining 24 women (40.7%) had some recovery, but for 15 of them (62.5%) the vein became a palpable cord. The feasibility of using a peripheral vein to perform chemotherapy decreased as the treatment progresses.(AU)

Exosomal transfer of circ_0006174 contributes to the chemoresistance of doxorubicin in colorectal cancer by depending on the miR-1205/CCND2 axis

Exosomes are the mediators of intercellular signal transduction, and they have been involved in the carcinogenesis and chemoresistance of tumor cells. Herein, we intended to investigate whether circular RNA (circRNA) circ_0006174 can regulate chemoresistance of doxorubicin (DOX) in colorectal cancer via exosomes. Forty-one pairs of normal and CRC (DOX sensitive, n = 16; DOX resistant, n = 25) samples were collected. The resistant cell lines (LoVo/DOX and HCT116/DOX) were constructed by exposure of parental cell lines (LoVo and HCT116) to DOX. The detection of circ_0006174, microRNA-1205 (miR-1205), and cyclin D2 (CCND2) was performed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell Counting Kit-8(CCK-8) was applied for determining the half of inhibitory concentration (IC50) of DOX and cell proliferation. The migration and invasion capacities were analyzed via transwell assay. Exosomes were extracted using ultracentrifugation. Protein levels were determined using western blot. Dual-luciferase reporter assay was used for affirming target interaction. In vivo experiment was performed by establishing xenograft models in mice. Circ_0006174 level was upregulated in DOX-resistant CRC tissues and cells. The downregulation of circ_0006174 inhibited DOX resistance, cell proliferation, migration, and invasion in DOX-resistant CRC cells. Interestingly, the abundant circ_0006174 was enriched in exosomes derived from DOX-resistant CRC cells. Furthermore, circ_0006174 could enhance DOX resistance via the exosomal intercellular transfer. Moreover, we validated the target relation of circ_0006174/miR-1205 or miR-1205/CCND2. The effect of exosomal circ_0006174 on DOX resistance was achieved by upregulating the miR-1205-mediated CCND2. In vivo, knockdown of circ_0006174 also enhanced tumor sensitivity to DOX by targeting miR-1205/CCND2 axis. (AU)

CIP2A silencing alleviates doxorubicin resistance in MCF7/ADR cells through activating PP2A and autophagy

Background Cancerous inhibitor of protein phosphatase 2A (CIP2A) plays a critical role in the pathogenesis of various types of cancer. Here, we investigated whether manipulating CIP2A abundance could enhance the treatment effects of doxorubicin in MCF-7/ADR cells. Methods CIP2A silencing was achieved by specific siRNAs. Proliferation of breast cancer cell line MCF-7/ADR under effective doxorubicin concentrations after CIP2A silencing was examined by MTT assay. Wound healing assay was performed to quantify cell migration and caspase-3/-7 activities were measured for assessing the extent of apoptosis. Results First, our data confirmed that MCF-7/ADR cell proliferation was suppressed by doxorubicin in a dose-dependent manner. Additionally, knocking down of CIP2A could further decrease MCF-7 cell proliferation and migration, even in the presence of doxorubicin. Mechanistically, we have found that CIP2A silencing promoted cell apoptosis relative to doxorubicin alone or vehicle control groups. Lastly, phosphatase2A (PP2A) activity was potentiated and the autophagy markers, LC3B and Beclin1, were upregulated after knocking down CIP2A. Conclusion Our findings support the potential benefits of using CIP2A inhibitor as a therapeutic agent to treat doxorubicin-resistant breast cancer (AU)

Simultaneous Kaposi's sarcoma and Castleman's disease in a HIV-negative patient. Response to rituximab and doxorubicin / Sarcoma de Kaposi y enfermedad de Castleman simultáneos en un paciente VIH negativo. Respuesta a rituximab y doxorrubicina

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Metástasis zosteriformes de porocarcinoma ecrino / Zosteriform Metastases From Eccrine Porocarcinoma

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Linfoma difuso de células B grandes pulmonar en paciente con neumonía intersticial no específica / Diffuse large B-cell lymphoma of the lung in a patient with nonspecific interstitial pneumonia

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Linfoma primario de corazón / Primary lymphoma of the heart

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Síndrome de secreción inadecuada de hormona antidiurética postquimioembolización transarterial de un carcinoma hepatocelular / Syndrome of inappropriate antidiuretic hormone secretion following transarterial chemoembolisation of hepatocellular carcinoma

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Aplicación de hipotermia en extremidades en la prevención de la eritrodisestesia palmo-plantar secundaria a administración de doxorrubicina liposomal pegilada / Applying hypothermia in extremities for the prevention of palmoplantar erythrodysesthesia secondary to the administration of pegylated liposomal doxor

La eritrodisestesia palmo-plantar o síndrome mano-pie es un efecto secundario de algunos tipos de quimioterapia. Se trata de una toxicidad cutánea que no pone en peligro la vida del paciente, pero sí que es dosis limitante y altera la calidad de vida. Se manifiesta en forma de eritema doloroso, a menudo precedido de parestesias en palmas de las manos y plantas de los pies, generando enrojecimiento, hinchazón y dolor, e incluso presencia de flictenas. Para su prevención y control existen medidas farmacológicas, pero también se utiliza la aplicación de crioterapia. Los cuidados de Enfermería son de gran importancia en el manejo de los síntomas, durante el tratamiento y el alivio de los efectos secundarios. El objetivo de este artículo es dar a conocer la eritrodisestesia palmo-plantar, así como aportar la experiencia clínica relacionada con la utilización de crioterapia preventiva mediante un caso clínico

Palmoplantar erythrodysesthesia or hand-foot syndrome is a side effect of some types of chemotherapy. This is skin toxicity not life-threatening for patients, but dose-limiting and with impact on Quality of Life. It appears as a painful erythema, often preceded by paresthesia in hand palms and feet soles, generating reddening, swelling and pain, and even the presence of phlyctenae. There are pharmacological measures for its prevention and control, but the application of cryotherapy can also be used. Nursing care is very important for symptom management, during treatment and relief of side effects. The objective of this article is to create awareness about palmoplantar erythrodysesthesia, as well as to offer the clinical experience associated with the use of preventive cryotherapy through a case report

Sarcoma de Kaposi palpebral bilateral en un paciente virus de la inmunodeficiencia humana negativo / Bilateral eyelid Kaposi's sarcoma in an HIV-negative patient

CASO CLÍNICO: Un varón de 70 años, procedente de Sicilia, acude con una masa palpebral bilateral con afectación tarsal conjuntival, que resultó ser un sarcoma de Kaposi al examen histológico. Se demostró afectación cutánea y pulmonar por el sarcoma de Kaposi. El paciente no tenía un diagnóstico previo de infección por el virus de la inmunodeficiencia humana. Este caso fue tratado con éxito tras 5 ciclos de quimioterapia con doxorrubicina liposomal, con resolución de las lesiones palpebrales, cutáneas y pulmonares. Conclusiones: La localización en el párpado es una posible manifestación inicial, aunque rara, del sarcoma de Kaposi en personas de edad avanzada negativos para el virus de la inmunodeficiencia humana. La doxorrubicina liposomal es un tratamiento seguro y efectivo

CASE REPORT: We report a case of 70-year-old male from Sicily, who presented with a bilateral eyelid mass involving the tarsal conjunctiva, found to be Kaposi's sarcoma on histologic examination. Cutaneous and pulmonary Kaposi's sarcoma involvement was documented. The patient had no prior diagnosis of human immunodeficiency virus infection. This case was managed successfully after the completion of five cycles of chemotherapy with liposomal doxorubicin, and his eyelid, skin and pulmonary lesions disappeared. CONCLUSIONS: Location in the eyelid is a possible, though rare, initial solitary manifestation of Kaposi's sarcoma in elderly HIV-negative patients. Liposomal doxorubicin is a safe and effective treatment

Evaluación económica del informe GENESIS-SEFH de olaratumab con doxorrubicina en el sarcoma de tejidos blandos en estadios avanzados / Economic evaluation of the GENESIS-SEFH report of olaratumab with doxorubicin in soft tissue sarcoma in advanced stages

Objetivo: Desarrollar la evaluación económica del fármaco olaratumab en el tratamiento del sarcoma de partes blandas. Método: Los datos se analizaron siguiendo las recomendaciones contenidas en el programa MADRE del modelo de informe GENESIS-SEFH. Resultados: Los resultados de supervivencia libre de progresión y supervivencia global publicados en el ensayo clínico pivotal: Tap WD y cols. (2016) fueron: la ganancia en supervivencia libre de progresión (variable principal) en términos absolutos fue de 2,5 meses, HR = 0,672; IC95% (0,442-1,021). La ganancia absoluta en supervivencia global (variable secundaria) fue de 11,8 meses, HR = 0,463; IC95% (0,301-0,710). Se realizó un análisis coste-efectividad considerando dos escenarios; escenario uno: sin aprovechamiento de viales; y escenario dos: sin aprovechamiento de viales y asociando costes no farmacológicos. En ambos casos se consideraron los costes de adquisición de los medicamentos y los datos de eficacia del ensayo clínico pivotal. En el primero determinamos una ratio coste-efectividad-incremental de 28.443,81 euros/mes libre de progresión ganado y 72.560,74 euros/año de vida ganado. En el segundo obtenemos una ratio coste-efectividad incremental de 30.879,79 euros libre de progresión ganado y 78.774,99 euros/año de vida ganado. El impacto económico estatal, por tanto, se situaría entre 61.759.592 millones de euros y 92.639.388 de euros, considerando una población diana de 800-1.200 pacientes a nivel nacional. Conclusiones: Olaratumab es un fármaco que aporta un beneficio significativo en la supervivencia global, no así en la supervivencia libre de progresión. Para poder utilizarse en el sarcoma de partes blancas y que resultase costeefectivo, el coste de adquisición del vial de 500 mg debería situarse entre 101,91 y 506,54 euros y el del vial de 190 mg entre 39,31 y 195,37 euros

Objective: The economic evaluation of the drug olaratumab is carried out in the treatment of soft tissue sarcoma. Method: The data were analyzed following the recommendations contained in the MADRE program of the GENESIS-SEFH report model. Results: Progression free survival and overall survival results published in the pivotal clinical trial; Tap WD et al. (2016) were improvement of 2.5 months in median progression free survival (primary endpoint) HR = 0.672; IC95% (0.442-1.021) and gain of 11.8 months in median OS (secondary endpoint) HR = 0.463; IC95% (0.301-0.710). A cost-effectiveness analyses was performed considering 2 scenarios; scenario 1: with use of whole vials and scenario 2: use of whole vials and associating non-pharmacological costs (day hospital visits, mucositis, neutropenia and dexrazoxane use). In both cases we considered the cost of drugs and the efficacy data of the pivotal clinical trial. In Scenario 1, we would have an Incremental-Cost-Effectiveness-Ratio of €28,443.81/ month of progression-free survival and €72,560.74 per year of life gained and in scenario 2 we would have an incremental-cost-effectivenessratio of €30,879.79/ progression-free survival and €78,774.99/ year of life gained. The budgetary impact of this drug would range from €61,759,592 to €92,639,388 estimated to be 800 to 1,200 patients likely to receive treatment in Spain. Conclusions: Olaratumab is a drug that provides a significant benefit in overall survival but not in progression free survival. To be used in soft tissue sarcoma and to be cost-effective, the acquisition cost of the 500 mg vial should be between €101.91 and €506.54 and that of the 190 mg vial between €39.31 and €195.37

Design, Synthesis and molecular docking study of hybrids of quinazolin-4(3H)-one as anticancer agents / Diseño, síntesis y estudio de acoplamiento molecular de híbridos de quinazolinona-tiazolidin-4-onas como agentes anticancerígenos

A series of 4-(2-(4-substituted phenyl)-4-oxoquinazolin-3(4H)-yl)-N-(2-(4-fluorophenyl)-4-oxo-5-(arylidene)thiazolidin-3-yl) benzamides (VIa-n) have been synthesized by condensation of N-(2-(4-fluorophenyl)-4-oxothiazolidin-3-yl)-4-(4-oxo-2-(4-substituted phenyl)quinazolin-3(4H)-yl)benzamides (Va-b) with various aryl/heteroaryl aldehydes using conventional methodology. All compounds were screened for their in vitro anticancer activity against the human breast cancer cell lines (MCF-7), human lung cancer cell lines (A549) using MTT assay method and doxorubicin is used as standard drug. Compound VId, VIk and VIn showed high potency against A549 cell lines with IC50 values 0.035±0.002 µM, 0.031±0.002 µM and 0.030±0.002 µM respectively compared to 0.023±0.002 µM showed by the standard. However, highest activity against MCF-7 cell lines was exhibited by Va, Vb, VIk and VIn with IC50 values between 0.040 - 0.050 µM. All the remaining compounds showed moderate anticancer activity against both the MCF-7 and A549 cell lines. To understand the interactions with active binding site of receptor, molecular docking study was also performed

Una serie de 2- (4-sustituido fenil) -4-oxoquinazolin-3 (4H) -il) -N- (2- (4-fluorofenil) -4-oxo-5- (arilideno) tiazolidin-3-ilo) benzamidas (VIa-n) han sido sintetizadas por condensación de N- (2- (4-fluorofenil) -4-oxotiazolidin-3-il) -4- (4-oxo-2- (4-fenil sustituido) quinazolin-3 (4H) -il) benzamidas (Va-b) con diversos aldehídos de arilo / heteroarilo usando metodología convencional. Todos los compuestos se cribaron para su actividad anticancerosa in vitro contra las líneas celulares de cáncer de mama humano (MCF-7), líneas celulares de cáncer de pulmón humano (A549) usando el método de ensayo MTT y se usa doxorrubicina como fármaco estándar. El compuesto VId, VIk y VIn mostraron alta potencia contra las líneas celulares A549 con valores IC50 de 0.035 ± 0.002 μM, 0.031 ± 0.002 μM y 0.030 ± 0.002 μM, respectivamente, en comparación con 0.023 ± 0.002 μM mostrada por el estándar. Sin embargo, la actividad más alta contra líneas celulares MCF-7 fue exhibida por Va, Vb, VIk y VIn con valores de CI50 entre 0.040 - 0.050 μM. Todos los compuestos restantes mostraron una actividad anticancerígena moderada contra las líneas celulares MCF-7 y A549. Para comprender las interacciones con el sitio de unión activa del receptor, también se realizó el estudio de acoplamiento molecular

Actualización del papel de la quimioterapia endovesical en el cáncer de vejiga no músculo-invasivo / Update on the role of endovesical chemotherapy in nonmuscle-invasive bladder cancer

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18F-FDG PET/TC en la estadificación inicial de pacientes con rabdomiosarcoma alveolar / 18F-FDG PET/CT as staging of alveolar rhabdomyosarcoma

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Múltiples nódulos pulmonares cavitados ¿tuberculosis o neoplasia maligna? / Multiple Cavitary Pulmonary Nodules. Tuberculosis or Malignancy?

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