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Mohammed Kashani-Sabet

Publications and source records attributed to Mohammed Kashani-Sabet.

At least 19 recordsLinked to original sources
PubMed2006

Prognostic significance of nuclear receptor coactivator-3 overexpression in primary cutaneous melanoma.

PURPOSE: To assess the prognostic significance of nuclear receptor coactivator-3 (NCOA3) overexpression in primary cutaneous melanoma. PATIENTS AND METHODS: NCOA3 expression was assessed using immunohistochemical analysis of a melanoma tissue microarray (TMA) containing primary melanomas from 343 patients with defined histology and follow-up. The impact of the presence or absence of various prognostic factors on relapse-free survival (RFS) and disease-specific survival (DSS) of melanoma patients was assessed using Cox regression and Kaplan-Meier analysis. The impact of presence or absence of various factors on sentinel lymph node (SLN) metastasis was assessed using logistic regression analysis. RESULTS: Increasing degree of NCOA3 expression was significantly predictive of SLN metastasis (P = .013) and the mean number of SLN metastases (P = .031). Kaplan-Meier analysis demonstrated a significant association between NCOA3 overexpression and reduced RFS (P = .021) and DSS (P = .030). Logistic regression analysis revealed increasing degree of NCOA3 expression to be an independent predictor of SLN status (P = .017). Multivariate Cox regression analysis showed the independent impact of NCOA3 expression on RFS (P = .0095) and DSS (P = .021). NCOA3 was the most powerful factor predicting DSS, outperforming tumor thickness and ulceration. CONCLUSION: These results identify NCOA3 as a novel, independent marker of melanoma outcome, with a significant impact on SLN metastasis, RFS, and DSS.

Biomarkers, Tumor↗
PubMed2006

Genes and pathways downstream of telomerase in melanoma metastasis.

Recent studies have demonstrated a role for telomerase in driving tumor progression, but its mechanism of action remains unclear. Here we show that stable, ribozyme-mediated suppression of mouse telomerase RNA reduced telomerase RNA expression, telomerase activity, and telomere length, which significantly reduced tumor invasion and metastatic potential. Our studies reveal that previously unidentified effects of telomerase may mediate its tumor-promoting effects. First, reducing telomerase activity induced a more dendritic morphology, accompanied by increased melanin content and increased expression of tyrosinase, a key enzyme in melanin biosynthesis. Second, gene expression profiling revealed that telomerase targeting down-regulated expression of several glycolytic pathway genes, with a corresponding decrease in glucose consumption and lactate production. Thus, telomerase activity controls the glycolytic pathway, potentially altering the energy state of tumor cells and thereby modulating tyrosinase activity and melanin production. These studies have important implications for understanding the mechanisms by which telomerase promotes tumor invasion and metastasis.

Animals↗
PubMed2006

Lymphatic drainage patterns of head and neck cutaneous melanoma observed on lymphoscintigraphy and sentinel lymph node biopsy.

BACKGROUND: The purpose of this study was to evaluate lymphatic drainage patterns of head and neck cutaneous melanoma observed on preoperative lymphoscintigraphy and sentinel lymph node biopsy (SLNB) and determine discordancy from clinically predicted lymphatic drainage patterns. METHODS: We conducted a retrospective chart review of 114 patients with head and neck cutaneous melanomas evaluated with preoperative lymphoscintigraphy and SLNB from January 2001 through July 2004. RESULTS: At least one sentinel lymph node (SLN) was identified in 97% of cases. On preoperative lymphoscintigraphy, an SLN was identified in an area not clinically predicted in 49 cases (43%). The most common sites of discordancy were in areas not typically dissected in standard neck dissections, such as the postauricular region, or in areas of more distant drainage than described previously, such as the inferior or posterior neck. Their percentages of discordant cases were 51%, 27%, and 22%, respectively. The sites of regional recurrence occurred in two cases not predicted on preoperative lymphoscintigraphy and in two cases of failed SLNB. CONCLUSIONS: On the basis of preoperative lymphoscintigraphy and the results of SLNB, head and neck cutaneous melanomas do have expected lymphatic drainage patterns despite perceived discordancy with previously clinically predicted drainage patterns that are based on standard neck dissection specimens. These "discordant" sites can still harbor melanoma, and all sites predicted on preoperative lymphoscintigraphy still need to be explored. The four cases of recurrences underscore the importance of close follow-up for all patients regardless of the SLNB result.

Adolescent↗
PubMed2006

Diagnosis of lymphoma in the draining lymph node basin at the time of in-transit metastasis of cutaneous melanoma.

The association between cutaneous melanoma and non-Hodgkin's lymphoma (NHL) has been described. Herein we describe two cases in which lymphoma was detected in the draining lymph node basin at the time of the finding of in-transit metastasis of cutaneous melanoma. In both of these cases, sentinel lymph node biopsy at the time of the excision of the primary melanoma showed no evidence of metastatic melanoma or lymphoma. The temporal and spatial correlation of melanoma and NHL in these two cases suggests the possibility of a local failure in immune surveillance.

Aged↗
PubMed2006

Prognostic significance of extent of ulceration in primary cutaneous melanoma.

Ulceration has been shown to be an adverse prognostic factor in primary cutaneous melanoma. However, the extent of ulceration required for histologic identification and biologic significance is unclear. We examined the impact of extent of ulceration on melanoma outcome in a cohort of 235 melanoma patients by evaluating the relationship between percentage of ulceration in the vertical growth phase of the primary tumor and 2 outcome parameters: sentinel lymph node status and overall survival. We measured the diameter of the ulcerated area in millimeters over the diameter of the entire vertical growth phase. There was a statistically significant relationship between increasing percentage of tumor ulceration and both sentinel lymph node status as well as overall survival, with a binary cut-off point of 2% for sentinel lymph node status and 5% for overall survival. The percentage of ulceration provides additional prognostic information in predicting sentinel lymph node status and in determining survival in melanoma patients. These results suggest that no more than minimal ulceration is required to have a prognostic impact on melanoma survival.

Adolescent↗
PubMed2006

Melanoma.

Explore the source record for details and available documents.

Algorithms↗
PubMed2005

The gene expression signatures of melanoma progression.

Because of the paucity of available tissue, little information has previously been available regarding the gene expression profiles of primary melanomas. To understand the molecular basis of melanoma progression, we compared the gene expression profiles of a series of nevi, primary melanomas, and melanoma metastases. We found that metastatic melanomas exhibit two dichotomous patterns of gene expression, which unexpectedly reflect gene expression differences already apparent in comparing laser-capture microdissected radial and vertical phases of a large primary melanoma. Unsupervised hierarchical clustering accurately separated nevi and primary melanomas. Multiclass significance analysis of microarrays comparing normal skin, nevi, primary melanomas, and the two types of metastatic melanoma identified 2,602 transcripts that significantly correlated with sample class. These results suggest that melanoma pathogenesis can be understood as a series of distinct molecular events. The gene expression signatures identified here provide the basis for developing new diagnostics and targeting therapies for patients with malignant melanoma.

Biopsy↗
PubMed2005

The role of microsatellites as a prognostic factor in primary malignant melanoma.

OBJECTIVE: To determine the impact of microsatellites as a prognostic factor in primary cutaneous melanoma. DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. Patients A total of 504 patients with a history of primary melanoma observed for 2 years or having experienced a first relapse. MAIN OUTCOME MEASURES: Overall survival (OS) and relapse-free survival (RFS). RESULTS: Forty-five patients had evidence of microsatellites in their primary melanoma. Presence of microsatellites significantly correlated with the presence of several other histologic high-risk factors such as tumor thickness, ulceration, Clark level, vascular factors, and mitotic rate. Univariate analysis demonstrated decreased RFS and OS in patients with microsatellites. Presence of microsatellites was associated with increased locoregional metastasis but not distant metastasis. In multivariate analysis, with the inclusion of 6 other clinical and histologic factors, presence of microsatellites was a significant predictor of RFS but not OS. Patients with clinical macrosatellites had a trend toward worsening OS compared with those with microsatellites. CONCLUSIONS: The presence of microsatellites is intimately tied to other markers of melanoma aggressiveness. Microsatellites appear to predict locoregional relapse and RFS but neither distant metastasis nor OS. These results may have implications for patient care as well as the inclusion of microsatellites in stage III of the current classification.

Analysis of Variance↗
PubMed2005

Clinical significance of occult metastatic melanoma in sentinel lymph nodes and other high-risk factors based on long-term follow-up.

Selective sentinel lymphadenectomy (SSL) following preoperative lymphoscintigraphy is the most significant recent advance in the management of patients with primary melanoma. This study evaluates the prognostic value of sentinel lymph node (SLN) status and other risk factors in predicting survival and recurrence in patients with primary cutaneous melanoma. From October 1993 to July 1998 a series of 412 patients with primary invasive melanoma underwent SSL at the UCSF/ Mt. Zion Melanoma Center. The outcome of 363 evaluable patients is summarized in this study. The factors related to survival and disease recurrence were analyzed by Cox proportional hazard regression models. The overall incidence of patients with positive SLNs was 18%. Over a median follow-up of 4.8 years, the overall mortality rate in patients with primary cutaneous melanoma was 18.7%, and 74 recurrences occurred (20.4%). Mortality was significantly related to SLN status [HR = 2.06; 95% Confidence interval (CI) 1.18, 3.58], angiolymphatic invasion (HR = 2.21; 95% CI 1.08, 4.55), ulceration (HR = 1.79; 95% CI 1.02, 3.15), mitotic index (HR =1.38; 95% CI 1.01, 1.90), and tumor thickness (HR = 2.20, 95% CI 1.21, 3.99). Factors significantly related to disease-free survival included SLN status (HR = 2.09; 95% CI 1.31, 3.34), tumor thickness (HR = 1.89; 95%. CI 1.20,2.98), and age (HR= 1.26 95% CI 1.08, 1.47). SLN status was the most significant factor for melanoma recurrence and death. Other important predictors include tumor thickness, ulceration, lymphatic invasion, and mitotic index.

Adult↗
PubMed2005

Neurotropic melanoma invading the inferior alveolar nerve.

BACKGROUND: Desmoplastic neurotropic melanoma (DNM) and neurotropic melanoma (NM), rare lesions of the head and neck, often present as a benign-appearing nodule which later progresses to cranial nerve involvement. OBJECTIVE: To discuss treatment and outcome of 3 cases of DNM/NM of the lower lip. METHODS: Three case reports with 12- to 54-month follow-up and literature review. RESULTS: The first case had an initial excision of melanoma of his lower lip and presented 16 years later with severe bilateral atrophy of his muscles of mastication with NM and underwent intensity modulated radiation therapy but no further resection. We also report two other cases of DNM of the lip, one of which received gamma knife radiosurgery for intracranial extension. LIMITATIONS: Small retrospective case series. CONCLUSIONS: Locoregional recurrences from DNM are more common than distant metastasis warranting vigilant surveillance following resection of the initial lesion. Radiation therapy and gamma knife radiosurgery may be used for cases of unresectable recurrences.

Adult↗
PubMed2005

A retrospective study of biochemotherapy for metastatic melanoma: the importance of dose intensity.

BACKGROUND: The utility of biochemotherapy for metastatic melanoma remains controversial. Dose intensity has been recognized as an important determinant of response and survival in the chemotherapy of several malignancies but has not been studied in biochemotherapy. In this retrospective study, we described the relationship between achieved dose intensity and the response rate of inpatient decrescendo biochemotherapy at our center. METHODS: A study of 38 consecutive patients with metastatic melanoma was undertaken. The planned doses were dacarbazine 800 mg/m(2) on day 1 or temozolomide 150 mg/m(2) on days 1-4, cisplatin 20 mg/m(2) on days 1-4, vinblastine 1.5 mg/m(2) on days 1-4, interferon-alpha-2b (Schering) 5 million IU (MIU)/m(2) on days 1-5, and interleukin-2 36 MIU on day 1, 18 MIU on day 2, and 9 MIU on days 3 and 4. RESULTS: Of 38 patients that received a total of 204 cycles of therapy, 8 (21%) complete responses and 14 (37%) partial responses were observed for an objective response rate of 58%. Median survival was 19.6 months. Achieved dose intensity was high with patients receiving 98.7% interleukin- 2, 87.1% interferon, 90.7% dacarbazine (DTIC), 94% temozolomide, 87.2% cisplatin, and 89.7% vinblastine. CONCLUSIONS: Six cycles of inpatient decrescendo biochemotherapy can be given with high-dose intensity and acceptable toxicity. High response rates with biochemotherapy for melanoma may correlate with dose intensity, dose density, and the number of cycles given on time.

Adult↗
PubMed2005

Heterogeneous patterns of lymphatic drainage to sentinel lymph nodes by primary melanoma from different anatomic sites.

UNLABELLED: We want to define the patterns of lymphatic drainage for primary melanoma to sentinel lymph nodes (SLNs) based on a large lymphoscintigraphic database. Preoperative lymphoscintigraphy was used to identify and classify SLN drainage basins and patterns of drainage. METHODS: Lymphoscintigraphy using intradermally administered technetium-99m labeled sulfur colloid was performed on 400 consecutive patients with malignant melanoma to define lymphatic drainage channels and draining SLN basins before surgery. Primary tumor sites consisted of head and neck, upper extremity, trunk, and lower extremity. Different types of drainage patterns were classified and correlated with different anatomic sites. RESULTS: SLN(s) were identified in over 98% of the patients, whereas lymphatic drainage channels were successfully identified in 90% of the patients. Drainage from the primary site to a single SLN through a single lymphatic channel (type IA) was seen in 186 of 400 patients (47%) as the most common type. In patients with a single SLN within a single basin (type I-V), the percentage of patients with primary lesions in the head and neck, upper extremity, trunk, and lower extremity regions were 61%, 79%, 55%, and 78%, respectively. In cases of multiple lymphatic channels (type VI-VII), the percentages of patients with primary lesions in the head and neck, upper extremity, trunk, and lower extremity regions were 24%, 8%, 36%, and 19%, respectively. CONCLUSION: Various drainage patterns were noted from primary melanomas in different anatomic sites. Preoperative lymphoscintigraphy is important in establishing the SLN basins for harvesting the SLN(s).

Humans↗
PubMed2005

Biomarkers for melanoma.

PURPOSE OF REVIEW: Given the capricious nature of melanoma, biomarkers that provide significant insight into the behavior of melanoma would greatly aid in identifying patients at risk for disease progression, those whose disease has progressed subclinically, and those who would benefit from currently available systemic therapies. This review focuses on molecular prognostic markers in primary melanoma, markers that aid in the detection of metastatic melanoma, and markers predictive of systemic therapy. RECENT FINDINGS: Significant advances have been made in the field of melanoma biomarkers. Utilization of paraffin-embedded tissue and multiple markers have improved the RT-PCR assays for detection of melanoma cells in lymph node tissue as well as peripheral blood. Lymphangiogenesis has been identified as a novel mechanism for melanoma progression, and candidate markers in the NF-kappaB signaling pathway have been identified to play a key role in melanoma: tumor vasculature interactions. Loss of heterozygosity has been used to identify potential candidates for biochemotherapy. Furthermore, serum S100B protein has been shown to be superior to lactate dehydrogenase in predicting prognosis and response to treatment for patients with advanced melanoma. SUMMARY: Although recent studies have contributed greatly to the development of melanoma markers, it is anticipated that the application of gene expression profiling and proteomics techniques to melanocytic neoplasms will result in the identification of even more effective biomarkers for melanoma than those currently in clinical use.

Biomarkers, Tumor↗
PubMed2005

Role of the head and neck surgeon in sentinel lymph node biopsy for cutaneous head and neck melanoma.

OBJECTIVE: To determine the reliability of sentinel lymph node biopsy (SLNB) in head and neck cutaneous melanomas to accurately stage nodal basins, describe techniques for safe SLNB in the neck and parotid regions, and discuss treatments. STUDY DESIGN: Retrospective chart review with follow-up mean of 11 months. METHODS: The charts of 80 patients treated for head and neck cutaneous malignancies from January 2001 through June 2003 were reviewed for presentation, treatment, and outcome. RESULTS: All patients received lymphoscintigraphy and SLNB for melanoma with Breslow thickness greater than 1 mm. Accurate preoperative lymphoscintigraphy and blue dye injection along with facial nerve monitoring when indicated correlated with safe SLNB. Eleven (14%) patients required completion surgery after positive SLNB and underwent evaluation for adjuvant therapies. There were three cases with complications: two postoperative hematomas and one seroma. CONCLUSIONS: Safe and reliable SLNB depends on the knowledge of the anatomy in the head and neck region, reliability of preoperative lymph node mapping with lymphoscintigraphy, and possible additions of blue dye injection and facial nerve monitoring. Complete surgical treatment of positive SLNB cases along with adjuvant therapies potentially improves control of these cutaneous malignancies with manageable morbidity.

Adolescent↗
PubMed2005

Cutaneous melanoma: prognostic factors.

BACKGROUND: Recent data have changed our views of prognostic factors in cutaneous melanoma. While some newer methods have yielded better prognostic information, some insights have evolved as a result of large-scale population-based analyses. METHODS: We review current data on several different prognostic factors and divide these factors according to their application in localized primary melanoma or metastatic melanoma. For each prognostic factor, the level of evidence supporting its use and its applicability to clinical practice are considered. RESULTS: For localized primary melanoma, the dominant predictors of survival include lesion thickness, ulceration, and lymph node involvement. Factors such as age, sex, anatomic location, and satellite/in-transit lesions are important in localized melanoma. Factors currently being investigated are tumor vascularity, vascular invasion, mitotic rate, tumor regression, and tumor-infiltrating lymphocytes. For metastatic melanoma, the most important prognostic factors are site of metastases and the presence of elevated serum lactic dehydrogenase. The value of these prognostic factors to clinicians caring for melanoma patients is discussed. CONCLUSIONS: A better understanding of prognostic factors in cutaneous melanoma has evolved over the last decade, allowing oncologists to provide appropriate treatment for their patients. Many of the prognostic factors are interrelated. In the near future, it is expected that several molecular genetic factors will provide more insight into the prognosis of patients with melanoma.

Humans↗
PubMed2004

An anti-Wnt-2 monoclonal antibody induces apoptosis in malignant melanoma cells and inhibits tumor growth.

Activation of the Wnt/beta-catenin signaling pathway has been associated with human cancers. To test whether Wnt-2 signal is a survival factor in human melanoma cells and thus represents a potential therapeutic target, we investigated the effects of inhibition of Wnt-2 signaling in human melanoma cell lines. We have developed a novel monoclonal antibody against the NH(2) terminus of the human Wnt-2 ligand that induces apoptosis in human melanoma cells overexpressing Wnt-2. Whereas incubation of this antibody with normal cells lacking Wnt-2 expression does not induce apoptosis, Wnt-2 signaling blockade by the ligand-binding antibody is confirmed by down-regulation of Dishevelled and beta-catenin. Wnt-2 small interfering RNA treatment in these cells yielded similar apoptotic effects and downstream changes. Down-regulation of an inhibitor of apoptosis family protein, survivin, was observed in both the Wnt-2 antibody-treated and small interfering RNA-treated melanoma cell lines, suggesting that the antibody induces apoptosis by inactivating survivin. In an in vivo study, this monoclonal anti-Wnt-2 antibody suppresses tumor growth in a xenograft model. These findings suggest that the anti-Wnt-2 monoclonal antibody may be useful for the treatment of patients with malignant melanoma.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Antitumor activity of systemically delivered ribozymes targeting murine telomerase RNA.

PURPOSE: To test ribozymes targeting mouse telomerase RNA (mTER) for suppression of the progression of B16-F10 murine melanoma metastases in vivo. EXPERIMENTAL DESIGN: Hammerhead ribozymes were designed to target mTER. The ribozyme sequences were cloned into a plasmid expression vector containing EBV genomic elements that substantially prolong expression of genes delivered in vivo. The activity of various antitelomerase ribozymes or control constructs was examined after i.v. injection of cationic liposome:DNA complexes containing control or ribozyme constructs. Expression of ribozymes and mTER at various time points were evaluated by quantitative real-time PCR. Telomerase activity was examined using the telomeric repeat amplification protocol. RESULTS: Systemic administration of cationic liposome:DNA complexes containing a plasmid-expressed ribozyme specifically targeting a cleavage site at mTER nucleotide 180 significantly reduced the metastatic progression of B16-F10 murine melanoma. The antitumor activity of the anti-TER 180 ribozyme in mice was abolished by a single inactivating base mutation in the ribozyme catalytic core. The EBV-based expression plasmid produced sustained levels of ribozyme expression for the full duration of the antitumor studies. In addition to antitumor activity, cationic liposome:DNA complex-based ribozyme treatment also produced reductions in both TER levels and telomerase enzymatic activity in tumor-bearing mice. CONCLUSIONS: Systemic, plasmid-based ribozymes specifically targeting TER can reduce both telomerase activity and metastatic progression in tumor-bearing hosts. The work reported here demonstrates the potential utility of plasmid-based anti-TER ribozymes in the therapy of melanoma metastasis.

Animals↗