José Torres

Weatherford College

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Christophe Gonçalves

Jewish General Hospital

Fan Huang

McGill University

Krikor Bijian

Jewish General Hospital

Qianyu Guo

Shanxi Academy of Medical Sciences

Sonia V. del Rincón

Jewish General Hospital

Moulay A. Alaoui‐Jamali

Jewish General Hospital

Antonio L. Cubilla

Universidad Nacional de Asunción

Mark Basik

McGill University

Wilson H. Miller

Jewish General Hospital

Fariba Behbod

University of Kansas Medical Center

Cooperative Institutions

Tanana Chiefs Conference

McGill University

Jewish General Hospital

University of Chile

Weatherford College

McGill University Health Centre

Hospital San Juan de Dios

Harvard University

Universitat de les Illes Balears

North Shore Diabetes and Endocrine Associates

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Effects of Polyphenols from Grape Seeds on Renal Lithiasis

Oxidative Medicine and Cellular Longevity (2015)

F. Gráses Rafael Prieto Rafel A. Fernandez-Cabot Antonia Costa‐Bauzá Fernando Tur

Nephrolithiasis is a complex disease that results from a combination of factors related to both urine composition and kidney morphoanatomy. Development of calcium oxalate monohydrate papillary calculi is linked to initial subepithelial calcification of renal papilla. Progressive tissue calcification depends on preexisting injury and involves reactive oxygen species. Many plant extracts that protect against oxidative stress manifest antilithiasic activity. Our study focused on determining the effects of polyphenols on a lithiasis rat model. Rats were pretreated with polyphenols and grape seed extracts, followed by posterior induction of hyperoxalosis via treatment with ethylene glycol plus NH4Cl. The concentrations of calcium and other elements in kidney were determined, along with histological examination of kidney and 24 h urine analysis. Significant differences were observed in the renal calcium content between the control plus ethylene glycol-treated group and the epicatechin plus ethylene glycol-treated, red grape seed extract plus ethylene glycol-treated, and white grape seed extract plus ethylene glycol-treated groups, with reductions of about 50%. The antioxidant activity of polyphenols extracted from red and white grape seeds may be critical in the prevention of calcium oxalate monohydrate papillary calculus formation, particularly if calculi are induced by lesions caused by cytotoxic compounds with oxidative capacity.

Ethylene Glycol Poisoning

10.1155/2015/813737

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Citations (35)

Pseudoglandular (Adenoid, Acantholytic) Penile Squamous Cell Carcinoma

The American Journal of Surgical Pathology (2009)

Isabela Werneck da Cunha Gustavo Cardoso Guimarães Fernando Augusto Soares Dominga Elsa Velázquez José Torres

Almost half of penile squamous cell carcinomas (SCCs) are of the usual type but there is a variegated spectrum of morphologically distinctive subtypes. In a pathologic review of 375 uniformly diagnosed and treated patients with penile SCC, we found 7 tumors with predominant pseudoglandular or adenoid features. The aim of the study was to delineate clinicopathologic features and outcome of an unusual variant of penile SCC. Clinical charts and pathologic materials were reviewed. The following informations were obtained: patient's age, tumor site, size, histologic grade (1, 2, and 3), thickness in millimeters, anatomic level of invasion [corpus spongiosum, corpus cavernosum (CC)], vascular and perineural invasion, groin nodal status, and follow-up in months. These features were compared with those of 224 cases of usual SCCs. Median age of the patients was 54 years. Tumors were large (average 4.6 cm) and involved multiple sites in 4 cases; exclusively the glans in 2 and site was unknown in 1. Microscopically, tumors were SCC with acantholytic areas ranging from solid nests with early necrosis or empty pseudoluminal spaces lined by 1 layer of squamous cells or cylindrical cells strikingly simulating glands. Tumors were deeply infiltrating (4 invaded CC, 2 corpus spongiosum, and 1 invaded preputial dermis) and were of high histologic grade (6 cases). Vascular invasion was present in 4 cases and perineural invasion in 2. The differential diagnosis was with gland forming penile tumors (surface adenosquamous, mucoepidermoid, and urethral adenocarcinomas) and the angiosarcomatoid variant of sarcomatoid carcinomas. There was regional nodal metastasis in 3 patients, 2 of which died from disease. The other 5 were either alive with no evidence of disease (12 and 21 y after diagnosis) or died from causes other than penile cancer (3, 4, and 7 y after diagnosis). Comparing with usual SCCs, pseudoglandular SCCs were of higher grade (88% vs. 44%), invaded deeper into CC (71% vs. 52%), and showed a higher incidence of regional metastasis (42% vs. 25%) and higher mortality (29% vs. 19%).

Perineural invasion

Corpus Spongiosum

Lymphovascular invasion

Adenoid

Pagetoid

10.1097/pas.0b013e31818a01d8

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Citations (61)

Malignant melanoma of the cervix. Report of a case.

PubMed (1988)

Holmquist Nd José Torres

A malignant melanoma of the cervix, a rare neoplasm, was found to have an unusual cytologic pattern, similar to that of a leiomyosarcoma. A biopsy sample was diagnosed as cervical malignant melanoma of the spindle cell type. Some neoplastic cells in the tissue contained melanin pigment, whereas none of the abnormal cells in the cervical scrapes, except for an abnormal giant cell, had visible cytoplasmic pigment. The abnormal cells in the cervical scrape specimen were spindle-shaped, as were their nuclei, which is why the cytologic pattern was interpreted as that of a leiomyosarcoma. Evidence from this and previously reported cases shows that malignant melanoma must be considered as a possible source of exfoliated abnormal nonpigmented spindle-shaped cells in a cervicovaginal cell sample.

Neoplasm

Cytopathology

Malignant Transformation

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Histologic Grade and Perineural Invasion are More Important Than Tumor Thickness as Predictor of Nodal Metastasis in Penile Squamous Cell Carcinoma Invading 5 to 10 mm

The American Journal of Surgical Pathology (2008)

Elsa F. Velázquez Gustavo Ayala Hao Liu Alcides Chaux Magali Zanotti

Penile squamous cell carcinomas (SCCs) invading to a depth inferior to 5 mm usually have very low risk for regional metastasis, whereas tumors thicker than 10 mm have a high metastatic potential. A significant number of squamous cell carcinomas, however, belong to an intermediate category (5 to 10 mm in thickness) in which the incidence of regional lymph node metastasis is very difficult to predict. Consequently, a frequent clinical dilemma is whether to perform or not inguinal dissection in this group of lesions. The objective of this study was to evaluate multiple risk factors for regional metastasis in tumors 5 to 10-mm thick. One hundred thirty-four partial penectomies with invasive carcinomas 5 to 10-mm thick, all of which with corresponding inguinal lymph node dissection, were evaluated. Factors evaluated were--patient's age, anatomic site, histologic grade, tumor thickness, anatomic levels of invasion, and vascular and perineural invasion. Grades were classified as 1, well; 2, moderately; and 3, poorly differentiated. To evaluate independent significance of various prognostic factors, a logistic regression analysis was performed, and a nomogram was prepared to evaluate metastatic risk according to histologic grade and perineural invasion. Groin metastasis was found in 66 of 134 patients (49%). High histologic grade and perineural invasion were statistically significant pathologic factors associated with groin metastasis. Nodal metastases were found in 2 of 25 grade 1 (8%), 24 of 46 grade 2 (52%), and 40 of 63 grade 3 carcinomas (63%) (P value 0.0001). Of 48 patients with perineural invasion, metastasis was found in 33 cases (69%) (P value 0.001). The average tumor thickness, anatomic level of invasion, and presence of vascular invasion were not statistically significantly different in metastasizing and nonmetastasizing neoplasms. Fifty percent of tumors invading 5 to 10 mm were not associated with metastasis and may be spared a nodal dissection. In this subset of patients, high histologic grade and perineural invasion were significant and useful risk factors associated with regional metastasis. The probability of inguinal node metastasis in patients with grade 1 tumors without perineural invasion is almost nonexistent whereas for high-grade tumors associated with perineural invasion is near 80%.

Perineural invasion

Groin

10.1097/pas.0b013e3181641365

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Citations (152)

Use of gold seeds in the treatment of prostate cancer IMRT.Implementing the NAL protocol for correction of motion of the prostate

F. Garcı́a‐Vicente V. Arroyo Fernández A. Autran Gomez A. Zapatero Inmaculada Fernández

Gold standard (test)

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MNK1/2 inhibition limits oncogenicity and metastasis of KIT-mutant melanoma

Journal of Clinical Investigation (2024)

Zhan Yao Jun Guo William Yang Christophe Gonçalves Tomasz Rzymski

10.1172/jci181338

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Data from MNK1/NODAL Signaling Promotes Invasive Progression of Breast Ductal Carcinoma In Situ

Qianyu Guo Vivian Z. Li Jessica N. Nichol Fan Huang William Yang

<div>AbstractThe mechanisms by which breast cancers progress from relatively indolent ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) are not well understood. However, this process is critical to the acquisition of metastatic potential. MAPK-interacting serine/threonine-protein kinase 1 (MNK1) signaling can promote cell invasion. NODAL, a morphogen essential for embryogenic patterning, is often reexpressed in breast cancer. Here we describe a MNK1/NODAL signaling axis that promotes DCIS progression to IDC. We generated MNK1 knockout (KO) or constitutively active MNK1 (caMNK1)-expressing human MCF-10A–derived DCIS cell lines, which were orthotopically injected into the mammary glands of mice. Loss of MNK1 repressed NODAL expression, inhibited DCIS to IDC conversion, and decreased tumor relapse and metastasis. Conversely, caMNK1 induced NODAL expression and promoted IDC. The MNK1/NODAL axis promoted cancer stem cell properties and invasion in vitro. The MNK1/2 inhibitor SEL201 blocked DCIS progression to invasive disease in vivo. In clinical samples, IDC and DCIS with microinvasion expressed higher levels of phospho-MNK1 and NODAL versus low-grade (invasion-free) DCIS. Cumulatively, our data support further development of MNK1 inhibitors as therapeutics for preventing invasive disease.Significance:These findings provide new mechanistic insight into progression of ductal carcinoma and support clinical application of MNK1 inhibitors to delay progression of indolent ductal carcinoma in situ to invasive ductal carcinoma.</div>

Nodal signaling

Tumor progression

10.1158/0008-5472.c.6511070.v1

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Dietary myo-inositol hexaphosphate prevents dystrophic calcifications in soft tissues: a pilot study in Wistar rats

Life Sciences (2004)

F. Gráses Joan Perelló Rafael Prieto B.M. Simonet José Torres

Dystrophic calcification

10.1016/j.lfs.2003.11.030

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Citations (49)

Human Papillomavirus???Related Lesions of the Penis

Pathology Case Reviews (2005)

Gustavo E. Ayala José Barreto Ingrid Rodr guez José Torres Antonio L. Cubilla

Human papillomavirus (HPV) can be associated with numerous lesions of the penis. Most of these are benign, such as condylomas, or preneoplastic lesions. In the later, HPV is found in almost all cases. It is therefore counterintuitive that HPV is present in only a portion of penile carcinomas, mainly basaloid and warty carcinomas. It is evident that the penile mucosa is relatively resistant to HPV oncogenesis and that invasive cancers arise only when the right conditions exist. Among these is the presence of foreskin, which appears to have a permissive role. HPV is transmitted sexually, and males are apparently a reservoir for this virus.

Foreskin

10.1097/01.pcr.0000153240.56295.2d

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Citations (1)

Angioplastía con balón para el tratamiento de la hipertensión arterial pulmonar por enfermedad tromboembólica crónica. Resultados hemodinámicos y clínicos inmediatos

Revista médica de Chile (2019)

Pablo Sepúlveda Juan F. Ortega Germán Armijo José Torres Pablo Ramírez

Balloon pulmonary angioplasty (BPA) is a therapeutic alternative for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH).To report the initial experience with the "refined BPA technique" with the use of intravascular images.Between June 2015 and June 2016 we selected fourteen patients with CTEPH who were considered candidates for BPA. Lesions targeted for treatment were further analyzed using intravascular imaging with optical frequency domain imaging (OFDI). We report the immediate hemodynamic results and four weeks of follow-up of the first eight patients of this series.We performed 16 BPA in eight patients aged 61 ± 14 years (88% women). Mean pulmonary artery pressure (PAPm) was 48.6 ± 5.8 mmHg. Success was achieved in seven patients (88%). A mean of 2.3 segments per patient were intervened in 11 sessions (1.6 sessions/ patient). Only one patient developed lung reperfusion injury. No mortality was associated with the procedure. After the last BPA session, PAPm decreased to 37.4 ± 8.6 mmHg (p=0.02). Pulmonary vascular resistance (RVP) decreased from 858,6 ± 377,0 at baseline to 516,6 ± 323,3 Dynes/sec/cm-5 (p<0.01) and the cardiac index increased from 2.4±0.6 at baseline to 2.8±0.3 L/min/m2 (p=0.01). At 4 weeks after the last BPA, WHO functional class improved from 3.3±0.5 to 2.5±0.5 (p<0,01) and six minutes walking distance from 331±92 to 451±149 m (p=0.01).BPA guided by OFDI for the treatment of inoperable CTEPH patients is a safe alternative with excellent immediate hemodynamic and clinical results.

10.4067/s0034-98872019000400426

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Citations (2)