Biomedical subjects

Victor G Prieto

Publications and source records attributed to Victor G Prieto.

At least 37 records · Page 2Linked to original sources

PubMed2006

Subcutaneous ossifying fibromyxoid tumor.

Ossifying fibromyxoid tumor (OFMT) is an uncommon neoplasm occurring predominantly in the deep soft tissues of the trunk and proximal extremities. The lineage of this rare tumor to date is still uncertain. We present a case of a subcutaneous OFMT that recurred 8 years after initial resection. The histological findings of the primary and recurrent lesions are compared along with the histologic features possibly associated with aggressiveness. Dermatopathologists should consider OFMT in the differential diagnosis of subcutaneous neoplasms with a myxoid matrix.

Diagnosis, Differential↗

PubMed2006

Polymorphisms in the DNA repair genes XPC, XPD, and XPG and risk of cutaneous melanoma: a case-control analysis.

Sunlight causes DNA damage, including bulky lesions that are removed effectively by the nucleotide-excision repair (NER) pathway. There are at least eight core NER proteins participating in the pathway, and genetic variations in their genes may alter NER functions. We hypothesized that some NER variants are associated with risk of cutaneous melanoma. In a hospital-based case-control study of 602 non-Hispanic White patients with cutaneous melanoma and 603 age- and sex-matched cancer-free controls, we genotyped five common non-synonymous single-nucleotide polymorphisms identified to date and assessed their associations with risk of cutaneous melanoma. We found that a significantly increased risk of cutaneous melanoma was associated with XPD 751Lys/Gln [adjusted odds ratio (OR), 1.55 and 95% confidence interval (95% CI), 1.12-2.16] and XPD 751Gln/Gln (OR, 1.66; 95% CI, 1.03-2.68) genotypes compared with the XPD 751Lys/Lys genotype as well as XPD312Asp/Asn (OR, 1.54; 95% CI, 1.11-2.12) and XPD312Asn/Asn (OR, 1.75; 95% CI, 1.05-2.90) genotypes compared with the XPD 312Asp/Asp genotype. This increased risk was not observed in the other three XPC and XPG single-nucleotide polymorphisms. Moreover, the number of the observed XPD at-risk genotypes (i.e., 312Asn/Asn+Asn/Asp and 751Gln/Gln+Lys/Gln) was associated with cutaneous melanoma risk in a dose-response manner (OR, 1.47; 95% CI, 0.97-2.23 for one at-risk genotype; OR, 1.83; 95% CI, 1.29-2.61 for two at-risk genotypes; P(trend) < 0.001). However, we found no evidence of any interaction between XPD genotypes with XPC and XPG genotypes or the known risk factors. We concluded that genetic variants of the XPD gene might serve as biomarkers for susceptibility to cutaneous melanoma.

Case-Control Studies↗

PubMed2005

In vitro sensitivity to ultraviolet B light and skin cancer risk: a case-control analysis.

BACKGROUND: Mutagen sensitivity, measured as mutagen-induced chromatid breaks per cell in primary lymphocytes in vitro, has been used to study susceptibility to various epithelial cancers. Patients with xeroderma pigmentosum are highly sensitive to ultraviolet (UV) light due to inherited defects in DNA repair and have a 1000-fold higher risk of UV-induced skin cancer than the general population. However, an association between UV-induced chromosomal aberrations and risk of skin cancer in the general population has not been established. METHODS: We assessed in vitro UVB-induced chromatid breaks in a hospital-based case-control study. The study included 469 patients with skin cancer (231 with nonmelanoma skin cancer [NMSC] and 238 with cutaneous malignant melanoma [CMM]) and 329 cancer-free control subjects. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two-sided. RESULTS: Compared with the frequency of UVB-induced chromatid breaks per cell in control subjects (mean = 0.28 breaks per cell, 95% CI = 0.27 to 0.30), that in NMSC patients (basal cell carcinoma [BCC], n = 143, mean = 0.36 breaks per cell, 95% CI = 0.33 to 0.39 and squamous cell carcinoma [SCC], n = 88, mean = 0.35 breaks per cell, 95% CI = 0.32 to 0.38) was higher (P = .001 and P < .001, respectively), but that in CMM case patients (mean = 0.30 breaks per cell, 95% CI = 0.28 to 0.33) was not (P = .22). A frequency of chromatid breaks per cell above the median of control subjects was associated with nearly threefold increased risks for BCC (OR = 2.78, 95% CI = 1.79 to 4.30) and SCC (OR = 2.62, 95% CI = 1.50 to 4.60), but not with an increased risk of CMM. A dose-response relationship was evident between mutagen sensitivity and risk for both BCC (Ptrend < .001) and SCC (Ptrend < .001). Multiplicative interactions between mutagen sensitivity and sun exposure variables on risk, particularly for sunburn in BCC and hair color, tanning ability, and family history of skin cancer in SCC, were seen for NMSC but not CMM. CONCLUSIONS: UVB-induced mutagen sensitivity may play a role in susceptibility to NMSC but not to CMM.

Adult↗

PubMed2005

Automated quantitative analysis of activator protein-2alpha subcellular expression in melanoma tissue microarrays correlates with survival prediction.

The activator protein-2alpha (AP-2) transcription factor plays a key role in regulating expression of genes involved in tumor growth and metastasis of human melanoma. We sought to assess the prognostic significance of AP-2 expression and its role in the transition of nevi to metastatic melanoma. Two cohorts were analyzed. One was a "progression" microarray containing melanoma specimens from M.D. Anderson Cancer Center representing 84 cases and the other was a retrospective cohort from Yale University representing 214 primary melanomas and 293 metastases. Analysis of total AP-2 expression using two quantitative systems [automated quantitative analysis (AQUA) and laser scanning cytometry (LSC)] revealed no correlation with diagnosis group. LSC analysis of the M.D. Anderson Cancer Center array showed that the number of cells expressing nuclear AP-2 was highest in the benign nevi group (11.85%) and significantly decreased in each phase of melanoma progression to 0.39% in the metastatic group. Both LSC and AQUA showed decreased nuclear AP-2 levels and increased cytoplasmic AP-2 that is directly proportional to progression. Neither nuclear nor cytoplasmic expression levels correlated with outcome. Intriguingly, the ratio of cytoplasmic to nuclear AP-2 predicted outcome in the entire population and in the primary tumors alone, demonstrating the power of the ratio to normalize for variations. Furthermore, the AP-2 ratio directly correlated with other clinicopathologic factors, including Breslow depth (R = 0.334, P < 0.001). We show that a high level of AP-2 expression in the cytoplasm relative to the nucleus correlates with poor prognosis and the loss of nuclear AP-2 expression is associated with malignant transformation and progression of melanoma.

Cell Nucleus↗

PubMed2005

Scleromyxedema: role of high-dose melphalan with autologous stem cell transplantation.

Scleromyxedema, the most severe manifestation of the spectrum of lichen myxedematosus, is characterized by cutaneous mucinosis, extracutaneous manifestations, and a monoclonal gammopathy. Seven of 8 patients evaluated at our center were treated with high-dose melphalan (180 mg/m(2) intravenously) and autologous peripheral blood stem cell transplantation, with marked improvement of gastrointestinal, central nervous system, pulmonary manifestations, and Karnofsky performance status. Five patients obtained a cutaneous complete remission and 2 patients had partial remissions. Three patients with slight progression in the skin at 12, 8, and 4 months after treatment received a second cycle of high-dose melphalan and had further symptomatic improvement. The lichen myxedematosus-scleromyxedema spectrum appears to be a continuum that requires the presence of a serum paraprotein and differs in severity of skin lesions, extracutaneous manifestations, and performance status. High-dose melphalan followed by autologous transplantation appears effective for improving the symptoms and systemic manifestations of scleromyxedema.

Adult↗

PubMed2005

A mutation-created novel intra-exonic pre-mRNA splice site causes constitutive activation of KIT in human gastrointestinal stromal tumors.

We report a new mechanism of aberrant pre-mRNA splicing resulting in constitutive activation of a mis-spliced oncoprotein (KIT) leading to malignancy (gastrointestinal stromal tumor) in contrast to loss of function of mis-spliced proteins resulting in diverse human diseases in the literature. The mechanisms of three consecutive molecular events, deletion of noncoding and coding regions encompassing the 3' authentic splice site, creation of a novel intra-exonic pre-mRNA 3' splice acceptor site leading to in-frame loss of 27 nucleotides (nine amino acids; Lys550-Lys558), and the mechanism of constitutive activation of the mis-spliced KIT are elucidated. Loss of a peptide in a critical location unleashed the protein from autoinhibition (as evidenced by three-dimensional structural analysis), causing KIT to become constitutively activated and resulting in the GIST phenotype. We also demonstrated that only one of the following two exonic splicing enhancers is sufficient for inclusion of the KIT exon 11 in vivo: AACCCATGT (nucleotides 2-10 from the 5' end, which are recognized by SC35, SRp55, and SF2/ASF) or GGTTGTTGAGG (nucleotides 27-37 from the 5' end, which are recognized by SC35 and SRp55), suggestive of exonic enhancer redundancy.

Alternative Splicing↗

PubMed2005

Mortality risk from squamous cell skin cancer.

PURPOSE: To identify nonmelanoma skin cancer patients with squamous cell carcinoma (SCC) who are at greatest risk of disease-specific mortality. PATIENTS AND METHODS: Prospectively enrolled patients with a minimum of one pathologically confirmed skin SCC lesion, definitive treatment of the SCC lesion(s) resulting in no evidence of disease, and at least 2 months of follow-up after definitive treatment were eligible for the present longitudinal analysis. They received comprehensive clinical, pathologic evaluations and follow-up for patterns of failure and mortality. RESULTS: We enrolled 210 patients (187 men and 23 women) with a total of 277 skin SCC lesions and a median enrollment age of 68 years (range, 34 to 95 years). Median follow-up of surviving patients was 22 months. Three-year overall and disease-specific survival (DSS) rates were 70% and 85%, respectively. In univariate analyses, the clinical-pathologic factors associated with adverse DSS were local recurrence at presentation (P = .05), invasion beyond subcutaneous tissues (P = .009), perineural invasion (P = .002), lesion size (P = .0003), and depth of invasion (P = .05). Statistical models identified a homogeneous high-risk group of patients with lesions > or = 4 cm, perineural invasion, and deep invasion beyond subcutaneous structures. Three-year DSS was 100% for patients with no risk factors versus 70% for patients with at least one risk factor. CONCLUSION: Lesion size > or = 4 cm and histologic evidence of perineural invasion and deep invasion beyond subcutaneous structures were the clinical-pathologic factors most significantly associated with disease-specific mortality in skin SCC.

Adult↗

PubMed2005

Neurothekeoma.

OBJECTIVES: The purpose of this study was to investigate and share the experiences at The University of Texas M. D. Anderson Cancer Center in diagnosing, treating, and following patients with neurothekeoma. We report 13 cases. STUDY DESIGN: Case series. The clinical, surgical, and pathology records of the 7 patients with neurothekeoma treated at M. D. Anderson Cancer Center were retrospectively reviewed. In addition, the pathology records of 6 patients reviewed by the Department of Pathology for diagnosis only were retrospectively reviewed. RESULTS: Nine patients were women. Their mean age was 30 years (median, 24 years). Six of the lesions were on the head or neck, 4 were on extremities, and 2 were on the trunk, and the location of 1 was not recorded. Two lesions had been previously diagnosed, histologically, as leiomyosarcomas, 1 as a malignant nodular hidradenoma, and 1 as a clear cell hidradenoma. All the lesions had the characteristic nested pattern of growth, with various degrees of myxoid background. Mitotic figures and marked cellular pleomorphism were not common. Six cases were treated with wide local excision. A lesion of the nasal ala was excised by using Mohs micrographic surgery. Most cases were limited to the dermis, but 2 lesions infiltrated subcutaneous tissue and skeletal muscle. All patients were without evidence of disease at 8 months median follow-up range (0 to 35 months). CONCLUSION: Neurothekeoma is a benign neoplasm occurring usually in women and commonly in the head and neck. Because it may be locally invasive, treatment with wide local excision using frozen section control of margins is recommended. Care must be taken in the pathologic diagnosis of cutaneous neoplasms, and neurothekeoma should be considered in the differential diagnosis for spindle cell lesions. SIGNIFICANCE: Neurothekeoma is commonly misdiagnosed, pathologically and clinically, and it can be treated successfully with surgical excision. EBM RATING: C.

Adolescent↗

PubMed2005

Expression of p63 in primary cutaneous adnexal neoplasms and adenocarcinoma metastatic to the skin.

p63, a recently identified homologue of the p53 gene, has been reported to be essential in the development of epithelia and is mainly expressed by basal and myoepithelial cells. The purpose of this study was to investigate the pattern of p63 expression in cutaneous adnexal neoplasms and to assess its possible value in the differential diagnosis of primary cutaneous neoplasms vs adenocarcinomas metastatic to the skin. Immunohistochemical analysis for p63 was performed on formalin-fixed, paraffin-embedded archival tissue from 20 benign adnexal tumors, 10 malignant adnexal tumors and 14 adenocarcinomas metastatic to the skin. The expression of p63 was evaluated in epidermal cells, skin appendages and metastatic tumor cells. p63 was consistently expressed in the basal and suprabasal cells of epidermis and cutaneous appendages, including the basal/myoepithelial cells of sweat glands. Out of 20 benign adnexal tumors, 13 (65%) showed strong (score 3) p63 expression; the remaining seven (35%) cases had score 2. All primary cutaneous carcinomas, including adenocarcinomas, expressed p63. In contrast, none of the metastatic adenocarcinomas to the skin was positive for p63 (P<0.001). Based on our findings, analysis of p63 expression may help in the differential diagnosis of primary vs metastatic cutaneous adenocarcinomas.

Adenocarcinoma↗

PubMed2005

Evaluation of pulsed light and radiofrequency combined for the treatment of acne vulgaris with histologic analysis of facial skin biopsies.

BACKGROUND: Light and radiofrequency (RF) devices have recently been used to treat acne in selected patients. OBJECTIVE: To investigate the safety and efficacy of a combination of pulsed light and RF energy for the treatment of acne. Materials and methods. Thirty-two patients with moderate acne were treated twice weekly for four weeks with the Aurora AC (Syneron Medical Ltd, Yokneam, Israel), a combination of pulsed light and RF energy. Twenty-five patients completed the study. In four patients, the number of hair follicles showing perifolliculitis, the diameters of hair follicles, the diameters of sebaceous glands, and expressions of heat shock protein 70 and procollagen-1 were evaluated before and after treatment. RESULTS: The mean lesion count was reduced by 47% (p < 0.05) after eight treatments. Adverse effects-erythema, tingling, and burning-were mild and temporary. The percentage of follicles with perifolliculitis decreased from 58% to 33%, sebaceous gland areas decreased from 0.092 mm2 to 0.07 mm2, and heat shock protein 70 and procollagen-1 expressions did not change. CONCLUSION: The combination of optical and RF energies may be an alternative nonablative modality for the treatment of moderate acne. Clinical improvement may be partly due to reductions in both perifollicular inflammation and sebaceous gland areas.

Acne Vulgaris↗

PubMed2005

Melanoma of the penis, scrotum and male urethra: a 40-year single institution experience.

PURPOSE: Genitourinary melanoma is rare and classically associated with a poor prognosis. We describe our experience with 10 patients with penile or urethral involvement. In addition, we present what is to our knowledge the largest reported series of melanoma of the scrotum (6 cases). MATERIALS AND METHODS: We reviewed the records of 16 men who presented consecutively to our institution with genitourinary melanoma between 1962 and 2000. Clinical and pathological characteristics were assessed, including Breslow thickness, primary surgical intervention and clinical course. RESULTS: Of 10 patients with penile or urethral melanoma 1997 American Joint Committee on Cancer melanoma pathological stage was T1 (depth less than 0.75 mm) in 4, T2 (0.75 to 1.5 mm) in 3 and T3 (1.51 to 4 mm) in 3. Only 1 of 4 patients with clinically palpable inguinal nodes had inguinal metastases at lymphadenectomy (BILND) and 3 who underwent prophylactic superficial BILND had negative findings. In 7 patients with T1-2N0M0 disease there were no local recurrences after wide local excision (WLE) or partial penectomy at a median followup of 35 months. Six of 7 men were rendered disease-free. One patient died of melanoma that developed at a second primary site. The 3 patients with T3 tumors who underwent partial (2) or radical (1) penectomy with or without BILND died of disease (2) or had progression (1). In all patients with penile melanoma the 5-year actuarial disease specific and recurrence-free survival rates were 80% and 60%, respectively, at a median followup of 39 months (range 20 to 210). Six patients with scrotal melanoma were treated with WLE without local recurrences. Three of the 6 patients had palpable inguinal nodes, of whom 2 died after chemotherapy for unresectable disease and 1 died of other causes 51 months after negative BILND. The 3 men with clinically negative groins who did not undergo prophylactic BILND had distant (1) or regional (2) metastases and died of disease. In patients with scrotal melanoma the 5-year actuarial disease specific and recurrence-free survival rates were 33.3% and 33.3%, respectively, at a median followup of 36 months. CONCLUSIONS: Partial penectomy or WLE provided effective local control for low stage penile or urethral melanomas and all scrotal lesions. Patients showing clinically positive, proven metastasis died despite appropriate surgical procedures and multi-agent chemotherapy. Prophylactic modified inguinal lymphadenectomy should be considered in select patients with penile, scrotal and anterior urethral melanoma.

Adult↗

PubMed2005

Loss of claudin-1 expression in tumor-associated vessels correlates with acquisition of metastatic phenotype in melanocytic neoplasms.

Claudins are a family of transmembrane proteins involved in cell-to-cell adhesion and are believed to be the main component of tight junctions. Recent studies have suggested that some metastatic solid tumors lack claudin expression. It is unknown whether claudins play a role in cutaneous melanoma. Immunohistochemical studies were performed on tissue microarrays containing 19 benign melanocytic nevi (BN), 21 dysplastic nevi (DN), 23 primary malignant melanomas (MMs), and 31 metastatic melanomas (MMMs) using a polyclonal anti-claudin-1 antibody. Immunoreactivity in tumor cells and associated vessels was graded by intensity and by percentage of reactive cells. Normal epidermis served as internal control (3+ labeling). Cases with at least 2+ labeling in more than 25% of the cells were considered positive. Claudin-1 expression was present in 37% of BN, 24% of DN, 26% of MM, and 3.2% of MMM. Tumor-associated vessels showed the following results: 11 of 19 (58%) in BN, 14 of 21 (67%) in DN, 17 of 23 (74%) in MM, and 6 of 31 (19%) in MMM. A significant loss of expression was noted between MMM and all other lesions in tumor cells and associated vessels. There was no significant difference between BN, DN, and MM. Within primary melanomas, there was a significant correlation between expression of claudin in tumor cells and Clark level/Breslow thickness. Also significant was a decreased expression of claudin in tumor vessels of lesions with higher Breslow thickness or Clark level. These data suggest that loss of claudin-1 may play a significant role in the acquisition of metastatic phenotype in cutaneous melanoma. Cohn ML, Goncharuk VN, Diwan AH, Zhang PS, Shen SS, Prieto VG. Loss of claudin-1 expression in tumor-associated vessels correlates with acquisition of metastatic phenotype in melanocytic neoplasms.

Blood Vessels↗

PubMed2005

Expression of androgen receptor coactivator ARA70/ELE1 in androgenic alopecia.

BACKGROUND: Androgens have been implicated in androgenic alopecia as evidenced by the increased cutaneous expression of androgen receptor (AR), 5alpha-reductase, and decreased aromatase. Abnormalities of the AR-signal transduction pathway probably participate in the development of androgenic alopecia. ARA70/ELE1 is an AR coactivator with two isoforms, one full-length form (ARA70alpha/ELE1alpha), and an internally deleted form (ARA70beta/ELE1beta). We decided to examine the cutaneous expression of both isoforms in male androgenic alopecia. METHODS: Formalin-fixed, paraffin-embedded tissue sections from seven subjects with androgenic alopecia with matched punch biopsies from non-balding and balding areas were examined by in situ hybridization. RESULTS: Expression of at least one of the two probes for ARA70/ELE1 was present in all phases of the hair-growth cycle in all epithelial hair structures except for the inner root sheath. The dermal papilla and hair bulb expressed only the short (beta) but not the long (alpha) form of ARA70/ELE1. In situ labeling for ARA70beta/ELE1beta was weaker in the dermal papilla of balding recipient areas than those from donor ones. CONCLUSIONS: Our data further support that the hair growth is regulated by androgens. The differential expression pattern of ARA70/ELE1 suggests that this key androgen receptor coactivator is involved in androgenic alopecia. Lee P, Zhu C-C, Sadick NS, Diwan AH, Zhang PS, Liu JS, Prieto VG. Expression of androgen receptor coactivator ARA70/ELE1 in androgenic alopecia.

Alopecia↗

PubMed2005

Effects of intense pulsed light and the 1,064 nm Nd:YAG laser on sun-damaged human skin: histologic and immunohistochemical analysis.

BACKGROUND: Nonablative methods may produce collagen synthesis in sun-damaged skin. OBJECTIVE: To study the effects of intense pulsed light (IPL) and 1,064 nm neodymium:yttrium-aluminum-garnet (Nd:YAG) laser: a histologic and immunohistochemical analysis of sun-damaged skin. MATERIALS AND METHODS: Nine subjects participated. Five subjects received five-monthly treatments with IPL (560 nm cutoff filter, 8 x 35 mm spot size, pulse duration 2.4/4.2 milliseconds, pulse delay 15 milliseconds, fluence 28-35 J/cm2). Four subjects received treatment with a 1,064 nm Nd:YAG laser (130 J/cm2, triple pulse, 7.0/7.0/7.0-millisecond pulse duration, 75-millisecond delay). Routine histology and immunohistochemistry on 2 mm punch biopsies were taken before treatment and then at 3 and 6 months. We quantified collagen in the upper dermis and expression of heat shock protein 70 and procollagen 1. RESULTS: Pretreatment specimens contained solar damage. After treatment with the 1,064 nm Nd:YAG laser, the amount of collagen in the papillary dermis was slightly thicker than in those subjects treated with the IPL device (nonsignificant differences). Scattered dendritic cells in the papillary and upper reticular dermis expressed heat shock protein 70 and procollagen 1 after treatment with either light device. CONCLUSION: Both the IPL and 1,064 nm Nd:YAG laser-induced heat activation of superficial dermal dendritic cells resulted in deposition of collagen in the papillary dermis without evident morphologic damage to the epidermis or dermis.

Female↗

PubMed2005

Primary Sézary syndrome commonly shows low-grade cytologic atypia and an absence of epidermotropism.

The dermatopathologic findings in cases of Sézary syndrome (SS) that arise in patients without a previous diagnosis of mycosis fungoides have not been well characterized. We evaluated the histologic findings in skin biopsy specimens from 31 patients with such primary SS and correlated them with clinical and hematologic parameters at the time of biopsy. The most characteristic histologic finding was the presence of a dermal perivascular lymphoid infiltrate, usually with mild to moderate cytologic atypia and variable numbers of eosinophils; epidermotropism was absent or minimal in 19 cases (61%). Reactive epidermal changes such as spongiosis, parakeratosis, and acanthosis also were present frequently (27 [87%], 17 [55%], 19 [61%] cases, respectively). The number of eosinophils present in skin biopsy specimens correlated with the level of peripheral blood lymphocytosis. In erythrodermic patients or patients with persistent xerosis and pruritus, it is important to carefully evaluate the degree of lymphocyte atypia in the dermal perivascular infiltrate and correlate with blood flow cytometric findings to diagnose primary SS. Many cases will lack the epidermotropism usually seen in mycosis fungoides.

Antigens, CD↗

PubMed2004

Up-regulation of Flotillin-2 is associated with melanoma progression and modulates expression of the thrombin receptor protease activated receptor 1.

Flotillin 2 (flot-2) is a highly conserved protein isolated from caveolae/lipid raft domains that tether growth factor receptors linked to signal transduction pathways. Flot-2 protein and mRNA were increased in tumorigenic and metastatic melanoma cell lines in vitro, and the immunostaining intensity increased substantially across a tissue array of melanocytic lesions. Flot-2 transfection transformed SB2 melanoma cells from nontumorigenic, nonmetastatic to highly tumorigenic and metastatic in a nude mouse xenograft model. SB2 cells stably transfected with the flot-2 cDNA (SB2-flot)-2 cells proliferated faster in the absence of serum, and their migration through Matrigel was additionally enhanced by thrombin. When SB2-flot-2 cells were compared with SB2-vector-control cells on a cancer gene pathway array, SB2-flot-2 cells had increased expression of protease activated receptor 1 (PAR-1) mRNA, a transmembrane, G-protein-coupled receptor involved in melanoma progression. PAR-1 and flot-2 were coimmunoprecipitated from SB2-flot-2 cells. Up-regulation of PAR-1 was additionally confirmed in SB2-flot-2 cells and melanoma cell lines. SB2-flot-2 cells transfected with flot-2-specific small-interfering RNAs made substantially less flot-2 and PAR-1 mRNA. In conclusion, flot-2 overexpression is associated with melanoma progression, with increased PAR-1 expression, and with transformation of SB2 melanoma cells to a highly metastatic line. Flot-2 binds to PAR-1, a known upstream mediator of major signal transduction pathways implicated in cell growth and metastasis, and may thereby influence tumor progression.

Animals↗

PubMed2004

Invasive cutaneous fungal infections requiring radical resection in cancer patients undergoing chemotherapy.

Invasive fungal infections have emerged as a significant problem in patients with cancer with the development of better systemic therapies for malignancy and more effective antibacterial agents. The currently available world published medical literature was reviewed on invasive fungal infections in cancer patients with specific attention devoted to the multidisciplinary role of surgery in refractory cutaneous cases. Infections can develop on the forearm where peripheral intravenous catheters had been inserted in cancer patients undergoing cytotoxic chemotherapy. Curative intent begins with systemic contemporary anti-fungal therapy. Following resolution of neutropenia, patients may require radical surgical debridement with negative margins of resection for complete eradication of the fungal infection. Although invasive fungal infections refractory to antifungal systemic therapy in immunocompromised patients undergoing chemotherapy are a rare event, it is critical for surgeons and other multidisciplinary clinicians to recognize these potentially life-threatening infections that may necessitate radical surgical resection for cure.

Adult↗

PubMed2004

A missense mutation in KIT kinase domain 1 correlates with imatinib resistance in gastrointestinal stromal tumors.

KIT gain of function mutations play an important role in the pathogenesis of gastrointestinal stromal tumors (GISTs). Imatinib is a selective tyrosine kinase inhibitor of ABL, platelet-derived growth factor receptor (PDGFR), and KIT and represents a new paradigm of targeted therapy against GISTs. Here we report for the first time that, after imatinib treatment, an additional specific and novel KIT mutation occurs in GISTs as they develop resistance to the drug. We studied 12 GIST patients with initial near-complete response to imatinib. Seven harbored mutations in KIT exon 11, and 5 harbored mutations in exon 9. Within 31 months, six imatinib-resistant rapidly progressive peritoneal implants (metastatic foci) developed in five patients. Quiescent residual GISTs persisted in seven patients. All six rapidly progressive imatinib-resistant implants from five patients show an identical novel KIT missense mutation, 1982T-->C, that resulted in Val654Ala in KIT tyrosine kinase domain 1. This novel mutation has never been reported before, is not present in pre-imatinib or post-imatinib residual quiescent GISTs, and is strongly correlated with imatinib resistance. Allelic-specific sequencing data show that this new mutation occurs in the allele that harbors original activation mutation of KIT.

Alleles↗