Application of Protein-Protein Interaction Network Analysis in Order to Identify Cervical Cancer miRNA and mRNA Biomarkers.

Cervical cancer (CC) is one of the world's most common and severe cancers. This cancer includes two histological types: squamous cell carcinoma (SCC) and adenocarcinoma (ADC). The current study aims at identifying novel potential candidate mRNA and miRNA biomarkers for SCC based on a protein-protein interaction (PPI) and miRNA-mRNA network analysis. The current project utilized a transcriptome profile for normal and SCC samples. First, the PPI network was constructed for the 1335 DEGs, and then, a significant gene module was extracted from the PPI network. Next, a list of miRNAs targeting module's genes was collected from the experimentally validated databases, and a miRNA-mRNA regulatory network was formed. After network analysis, four driver genes were selected from the module's genes including MCM2, MCM10, POLA1, and TONSL and introduced as potential candidate biomarkers for SCC. In addition, two hub miRNAs, including miR-193b-3p and miR-615-3p, were selected from the miRNA-mRNA regulatory network and reported as possible candidate biomarkers. In summary, six potential candidate RNA-based biomarkers consist of four genes containing MCM2, MCM10, POLA1, and TONSL, and two miRNAs containing miR-193b-3p and miR-615-3p are opposed as potential candidate biomarkers for CC.

Treatment of basal cell carcinoma with intralesional interferon alfa-2b: an open-label clinical trial.

INTRODUCTION: Basal cell carcinoma (BCC) is the most common cutaneous cancer. We report the efficacy and aesthetic outcome of intralesional IFN-α 2b injection for the treatment of BCC and compare with the surgical method. MATERIALS AND METHODS: Intralesional IFN-α 2b was injected in 58 BCC lesions from 20 patients three times a week for three weeks. Control group was retrospectively selected among patients who underwent surgical method (standard surgical excision) for BCC including 58 lesions from 24 patients. All patients were followed up for one year in terms of recurrence and cosmetic outcome. RESULTS: Two patients (four lesions) failed to complete the treatment period. After three weeks, 40 (68.96%) lesions were completely cured. Nine (15.51%) lesions achieved complete healing in less than 9 sessions. Five (8.62%) lesions were completely cured by an extra week of injection. In aggregate, complete healing was observed in 54 (93.10%) lesions. In the surgery group, complete lesion elimination was detected in 52 (89.65%) lesions (p = 0.40). After one year, cosmetic outcome was significantly more favorable in the study group compared to the surgery group (p = 0.003). Recurrence was not detected in any of the groups after one year follow-up. CONCLUSION: Intralesional IFN-α 2b injection is an appropriate treatment choice for BCC. CLINICAL TRIAL REGISTRY: We used Iranian registery of Clinical trials; The IRCT code is: 2017093017756N30.

Assessment the Effect of Human Umbilical Cord Wharton's Jelly Stem Cells on the Expression of Homing Genes; CXCR4 and VLA-4 in Cell Line of Breast Cancer.

Background: Breast cancer is the most common cancer in women.  The prevalence of breast cancer in Western women is one in eight.  Although the prevalence of breast cancer in Iran is lower than in Western countries (one in every 10-12 women), the incidence of breast cancer in it is 5-10 years earlier than in Western countries. Breast cancer is the second leading cause of cancer death among women after lung cancer. Therefore, finding new therapeutic methods could potentially help to reduce breast cancer mortality and increase the survival rate. Wharton jelly stem cells with mesenchymal morphology play an important role in inhibiting the progression of ovarian, osteosarcoma, and breast cancer by inducing apoptosis and reducing metastasis. Several environmental and genetic factors are involved in the occurrence of breast cancer. CXCR4 and VLA-4 genes are important genetic factors in breast cancer that play a role in cell survival, migration, proliferation, and metastasis of several types of cancer, especially breast cancer. Therefore, inhibition of these two genes by Wharton's Jelly Stem Cells could be a novel and effective therapeutic target in breast cancer.  The aim of this study was to investigate the effect of Wharton jelly stem cells secretion on the expression of CXCR4 and VLA-4 genes in cancer cells. Materials and Methods: These cells were exposed to Wharton's Jelly Stem Cells after culturing breast cancer cells. RNA was extracted from treated cells. The expression of CXCR4 and VLA-4 genes was evaluated by real-time PCR. Results: The results of the MTT and Scratching tests showed a significant difference compared to the control group. Also, the results of Real-time PCR showed a significant decrease in the expression of CXCR4 and VLA-4 genes compared to the control group. Conclusion: The results of this study showed that different concentrations of Wharton Jelly Stem Cells reduce cancer cell growth and expression of CXCR4 and VLA-4 homing genes in MDA-MB-231 breast cancer cells. Therefore, Wharton Jelly Stem Cells can be considered as an effective treatment for breast cancer.

Drug repositioning in non-small cell lung cancer (NSCLC) using gene co-expression and drug-gene interaction networks analysis.

Lung cancer is the most common cancer in men and women. This cancer is divided into two main types, namely non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Around 85 to 90 percent of lung cancers are NSCLC. Repositioning potent candidate drugs in NSCLC treatment is one of the important topics in cancer studies. Drug repositioning (DR) or drug repurposing is a method for identifying new therapeutic uses of existing drugs. The current study applies a computational drug repositioning method to identify candidate drugs to treat NSCLC patients. To this end, at first, the transcriptomics profile of NSCLC and healthy (control) samples was obtained from the GEO database with the accession number GSE21933. Then, the gene co-expression network was reconstructed for NSCLC samples using the WGCNA, and two significant purple and magenta gene modules were extracted. Next, a list of transcription factor genes that regulate purple and magenta modules' genes was extracted from the TRRUST V2.0 online database, and the TF-TG (transcription factors-target genes) network was drawn. Afterward, a list of drugs targeting TF-TG genes was obtained from the DGIdb V4.0 database, and two drug-gene interaction networks, including drug-TG and drug-TF, were drawn. After analyzing gene co-expression TF-TG, and drug-gene interaction networks, 16 drugs were selected as potent candidates for NSCLC treatment. Out of 16 selected drugs, nine drugs, namely Methotrexate, Olanzapine, Haloperidol, Fluorouracil, Nifedipine, Paclitaxel, Verapamil, Dexamethasone, and Docetaxel, were chosen from the drug-TG sub-network. In addition, nine drugs, including Cisplatin, Daunorubicin, Dexamethasone, Methotrexate, Hydrocortisone, Doxorubicin, Azacitidine, Vorinostat, and Doxorubicin Hydrochloride, were selected from the drug-TF sub-network. Methotrexate and Dexamethasone are common in drug-TG and drug-TF sub-networks. In conclusion, this study proposed 16 drugs as potent candidates for NSCLC treatment through analyzing gene co-expression, TF-TG, and drug-gene interaction networks.

Assessment the Effect of Human Umbilical Cord Wharton's Jelly Stem Cells on the Expression of Homing Genes: CXCR4 and VLA-4 in Cell Line of Prostate Cancer.

Background : Prostate cancer is the second most common cancer in the male that affects the health, social and economic life of person. Different compounds such as Wharton's jelly, have been used to treat prostate cancer. Wharton's jelly is a tissue rich in cells with mesenchymal morphology. Wharton's jelly compound inhibited the growth of various cancer cells, including ovarian, osteosarcoma, breast, and prostate cancers, and also reduced the expression of CXCR4 and VLA-4 genes involved in the metastasis process. Materials and Methods: To do this research, Wharton's jelly stem cells and DU145 cancer cell line were cultured. After cell culture, the effect of Wharton's jelly on this cell line was evaluated by scratching and MTT assay. The expression of CXCR4 and VLA-4 genes was also evaluated by Real-time PCR. Results: The results of MTT and Scratching tests showed that Wharton's jelly inhibited the growth of DU145 cancer cells and also decreased the expression level of CXCR4 and VLA-4 genes. Conclusion: The results of this study showed that Wharton's jelly can be considered as an effective compound for decreasing metastasis of prostate cancer.

Human Wharton's jelly stem cells inhibit endometriosis through apoptosis induction.

Endometriosis is a relatively benign disease characterized by endometrial tumors and uterus stroma. Apoptosis suppression is one of the most important pathological processes of endometriosis. Recently, several studies reported that human Wharton's jelly stem cells (hWJSCs) can inhibit growth and proliferation of various cancer cells through induction of apoptosis. Therefore, the aim of the present study was to investigate the effects of hWJSCs conditioned medium (hWJSC-CM) and cell-free lysate (hWJSC-CL) on endometriosis cells in vitro. In the present study, effects of different concentrations of hWJSC-CM and hWJSC-CL on viability and proliferation, morphological alterations, colony formation, migration, invasion, and apoptosis of endometriosis cells were evaluated. Our results showed that hWJSC-CM and hWJSC-CL decrease viability and proliferation, colony formation, migration, and invasion, as well as increase morphological alterations and apoptosis of endometriosis cells, in a concentration- and time-dependent manner. Decreased migration and invasion of treated endometriosis cells with hWJSC-CM and hWJSC-CL may be due to decrease of MMP-2 and MMP-9 gene expression. Moreover, induction of apoptosis in treated endometriosis cells can be due to regulation of apoptosis-related genes expression, including BAX, BCL-2, SMAC, and SURVIVIN. The results of the present study suggest that hWJSC-CM and hWJSC-CL can inhibit endometriosis cells at a mild-to-moderate level through various physiological mechanisms. However, further studies on animal models are necessary to achieve more accurate results.

Psoralen and narrowband UVB combination provides higher efficacy in treating vitiligo compared with narrowband UVB alone: A randomised clinical trial.

BACKGROUND/OBJECTIVES: Side effects of current treatments and the need for a safe treatment with higher efficiency necessitate seeking new treatment options for vitiligo. Few studies have investigated the combination of psoralen with narrowband ultraviolet B (NBUVB). In this study, we compared the efficacy and safety of psoralen and NBUVB combination (P-NBUVB) with NBUVB alone in treatment of vitiligo. METHODS: This randomised clinical trial was carried out during 2015-2017 in dermatology clinics of Ghaem and Imam Reza hospitals, Mashhad, Iran on 40 vitiligo patients with 5-60% body involvement. The patients were randomly divided into two groups of NBUVB alone and P-NBUVB. Both groups underwent 60 phototherapy sessions (three sessions per week), and the repigmentation rate was measured using vitiligo area severity index (VASI) score. SPSS v. 16 software and appropriate statistical tests were used to analyse the data. P < 0.05 was considered statistically significant. RESULTS: The mean age of patients was 33.9 ± 11.3 years. Twenty patients (50%) were females. The P-NBUVB group showed greater VASI improvement in lower extremities (P = 0.003) and overall (P = 0.026) compared with NBUVB group. Moreover, the treatment response appeared sooner in P-NUVB group. CONCLUSION: Based on our results, we can conclude that adding psoralen to NBUVB phototherapy can result in increased efficacy. However, more studies are needed to evaluate the long-term effects and side effects of this treatment.

Fish tank granuloma: An emerging skin disease in Iran mimicking Cutaneous Leishmaniasis.

OBJECTIVE: Mycobacterium marinum causes a rare cutaneous disease known as fish tank granuloma (FTG). The disease manifestations resemble those associated with Cutaneous Leishmaniasis (CL). The aim of this study was to determine whether FTG was the cause of cutaneous lesions in patients who were referred to the Parasitology laboratory of Imam Reza Hospital in Mashhad to be investigated for CL. MATERIALS/METHODS: One hundered patients, clinically diagnosed with CL between April 2014 and March 2015, were included in this study. Ziehl-Neelsen staining was performed to identify acid-fast Mycobacterium in addition to bacterial cultures using Löwenstein-Jensen medium. Skin lesion samples were also collected and kept on DNA banking cards for PCR testing. RESULTS: Twenty-nine of the 100 individuals with skin lesions, and therefore suspected of suffering from CL, tested positive for Mycobacterium marinum by PCR. Of these, 21 (72.4%) were male and 8(27.6%) were female. In 97% of these cases the lesions were located on hands and fingers. These patients had a history of manipulating fish and had been in contact with aquarium water. A sporotrichoid appearance was observed in 58.6% of the patients with mycobacterial lesions; 67% of patients had multiple head appearance. CONCLUSION: Patients suspected to have CL and who test negative for CL could be affected by FTG. Therefore, after obtaining an accurate case history, molecular diagnosis is recommended for cases that give a negative result by conventional methods.

Efficacy of fractional CO2 laser in treatment of atrophic scar of cutaneous leishmaniasis.

Cutaneous leishmaniasis is an endemic disease in Iran. Unfortunately, it can lead to unsightly atrophic scars with limited treatment options. Fractional CO2 laser is accepted for treatment of atrophic acne scars and recently has been used to treat cutaneous leishmaniasis, so we planned to use fractional CO2 laser on leishmaniasis scar. We conducted this study on 60 leishmaniasis scars on the face of 40 patients. The lesions were treated by a fractional CO2 laser with beam size of 120 µm, with energy of 50-90 mJ, and 50-100 spots/cm(2) density with two passes in three monthly sessions. Evaluation was done in the first and second months after the first treatment and 3 and 6 months after the last treatment. Digital photography was performed at each visit. Assessment of improvement rate by patient and physician was rated separately as follows: no improvement (0%), mild (<25%), moderate (25-50%), good (51-75%), and excellent (76-100%). Based on patients' opinion, in the first and second follow-up, 48.3 and 90% of them reported moderate to excellent healing, respectively (p < 0.001). In 3 and 6 months follow-up after the end of the experiment, most of the patients (88.3 and 95%, respectively) reported moderate to excellent healing of scars. Based on two observers' opinion, healing in the first follow-up in most of the patients (65%) was mild to moderate and 33% were reported as having no healing. In the second follow-up, only 5% of the patients were reported with no healing and 60% were reported as having moderate healing (p < 0.001). In 3 and 6 months follow-up, most of the patients (95 and 96.6%) were reported as having moderate to excellent healing (p = <0.001). Our results underlined the high efficacy of fractional CO2 laser for leishmaniasis scar. No significant adverse effects were noted.

Serum 25-OH Vitamin D Level in Psoriatic Patients and Comparison With Control Subjects.

BACKGROUND: Vitamin D has been shown to have immunomodulatory effects, and previous studies have proposed a role of vitamin D deficiency in multiple autoimmune diseases, including psoriasis. OBJECTIVES: The aim of this study was to investigate serum vitamin D levels in psoriatic patients and compare them with levels in controls. METHODS: This study was carried out in 50 psoriasis patients. Serum vitamin D was measured by enzyme-linked immunosorbent assay. RESULTS: The mean serum vitamin D levels in psoriatic patients and controls were 14.92 ± 6.31 and 12.52 ± 4.54 ng/mL, respectively. The difference was not statistically significant (P = .06). The prevalence of vitamin D deficiency (<20 ng/mL) was 84.0% in psoriatic patients and 93.0% in controls (P = .21). CONCLUSIONS: Most of the patients with psoriasis had vitamin D deficiency, which may have contributed to the evolution of their psoriasis. However, considering the high prevalence of vitamin D deficiency in Iran, no difference was noted between the psoriatic patients and the controls.

Epidermal hydration and skin surface lipids in patients with long-term complications of sulfur mustard poisoning.

BACKGROUND: Despite almost the three decades passed since the chemical attacks of Iraqi's army against the Iranian troops, some veterans are still suffering from long-term complications of sulfur mustard (SM) poisoning, including certain skin complaints specially dryness, burning, and pruritus. We thus aimed to evaluate the skin's water and lipid content in patients with a disability of >25% due to complications of SM poisoning and compare them with a matched control group. MATERIALS AND METHODS: Sixty-nine male participants were included in this study; 43 SM-exposed patients, and 26 normal controls from their close relatives. The water and lipid content was measured in four different locations: Extensor and flexor sides of forearms and lateral and medial sides of legs by the Corneometer CM 820/Sebumeter SM 810. Collected data was analyzed and P ≤ 0.05 was considered as statistically significant. RESULTS: The mean age of the patients and controls was 49.53 ± 11.34 (ranges: 40-71) and 29.08 ± 8.836 (ranges: 15-49 years), respectively. In the veterans group, the main cutaneous complaint was itching and skin dryness. Cherry angioma, dry skin, and pruritus were significantly more common in the SM-exposed cases than in the controls. (P = 0.01, 0.05, and 0.04, respectively). The moisture and lipid content of all areas were lower in the SM-exposed group, but it was only significant in skin sebum of lateral sides of legs (P = 0.02). CONCLUSION: Exposure to SM could decrease the function of stratum corneum and lipid production as a barrier, even after several years of its exposure.

Stem cell therapy of cataract.

INTRODUCTION: Cataract is recognized as a disease of the lens resulting in many blindness cases, while the only therapeutic procedure is surgery. Thus, to tackle this disease, alternative methods are required. Stem cell therapy is one of the alternative treatment modalities. Paired lens' epithelial pieces induced by vitreous body were shown to produce lens-like structures. Here, Wharton's jelly derived stem cells are suggested as the best candidates for this purpose, as these cells have potency for the differentiation into the lens fiber cells. HYPOTHESIS: It is hypothesized that Wharton's jelly derived stem cells could be used as a novel and appropriate source for the treatment of cataract. Evaluation of HYPOTHESIS: To attain this aim, lens of an animal model of cataract can be removed. Then, the human Wharton's jelly stem cells (hWJSCs) are injected into a capsule. Finally, the expression of crystalline proteins and vision function are analyzed. CONCLUSION: It is hypothesized that the lens capsule could act as a natural scaffold and hWJSCs could be used to restore the lens structure in the empty capsule.

Comparison of mesenchymal stem cell markers in multiple human adult stem cells.

OBJECTIVES: Mesenchymal stem cells (MSCs) are adult stem cells which identified by adherence to plastic, expression of cell surface markers including CD44, CD90, CD105, CD106, CD166, and Stro-1, lack of the expression of hematopoietic markers, no immunogenic effect and replacement of damaged tissues. These properties led to development of progressive methods to isolation and characterization of MSCs from various sources for therapeutic applications in regenerative medicine. METHODS: We isolated MSC-like cells from testis biopsies, ovary, hair follicle and umbilical cord Wharton's jelly and investigated the expression of specific cell surface antigens using flow cytometry in order to verify stemness properties of these cells. RESULTS: All four cell types adhered to plastic culture flask a few days after primary culture. All our cells positively expressed common MSC- specific cell surface markers. Moreover, our results revealed the expression of CD19and CD45 antigens in these cells. CONCLUSION: According to our results, high expression of CD44 in spermatogonial stem cells (SSCs), hair follicle stem cells (HFSCs),granulosa cells (GCs)and Wharton's jelly- MSCs (WJ-MSCs)may help them to maintain stemness properties. Furthermore, we suggest that CD105+SSCs, HFSCs and WJ-MSCs revealed the osteogenic potential of these cells. Moreover, high expression of CD90 in SSCs and HFSCs may associate to higher growth and differentiation potential of these cells. Further, the presence of CD19 on SSCs and GCs may help them to efficiency in response to trans-membrane signals. Thus, these four types of MSCs may be useful in clinical applications and cell therapy.

Biological parameters influencing the human umbilical cord-derived mesenchymal stem cells' response to retinoic acid.

Human umbilical cord-derived mesenchymal stem cells (HUCMSCs) are multipotent fetal stem cells that differentiate into various cell lineages. In recent years, they have gained attention for therapeutic applications but very little is known about their sensitivity to chemical agents such as widely used retinoic acid (RA). As a morphogen inducing differentiation of mesenchymal stem cells, RA has for a long time been known to be a potent teratogen promoting craniofacial and limb abnormality in vertebrate embryos. Here, using MTT assay and EB/AO staining as well as TUNEL assay we show that RA in a concentration-dependent manner induces apoptosis through upregulating Caspase expression and increasing Bax/Bcl2 ratio. Moreover, different biological parameters such as initial time seeding, cell density, passage number and duration of RA treatment play a major role in HUCMSCs cytotoxic response to this agent.

Prognostic significance of sentinel lymph node mapping in Merkel cell carcinoma: systematic review and meta-analysis of prognostic studies.

AIM: To assess through a systematic review and meta-analysis of the literature the prognostic implication of sentinel lymph node mapping in Merkel cell carcinoma (MCC). MATERIALS AND METHODS: PubMed and SCOPUS databases were searched by using "Merkel AND sentinel" as keywords. All studies with prognostic information regarding SLN mapping in cN0 MCC patients were included. Hazard ratio (HR) for overall survival (OS) and disease free survival (DFS) was used as effect size. RESULTS: SLN biopsy predicted better DFS and OS as compared to the nodal observation in cN0 MCC patients (pooled HR for DFS: 1.61 (95% CI: 1.05-2.46), P = 0.028; pooled HR for OS: 1.08 (95% CI: 0.55-2.10), P = 0.8). Pathologically negative SLN (SLN-) patients had better OS (pooled HR: 4.42 (95% CI: 1.82-10.7), P = 0.0009) and DFS (pooled HR: 2.58 (95% CI: 1.78-3.73)) as compared to SLN+ patients. CONCLUSION: SLN mapping can provide strong prognostic information regarding OS and DFS in cN0 MCC patients. More importantly, SLN mapping can improve DFS and possibly OS in cN0 MCC patients as compared to nodal observation. As MCC is a rare tumor, large multicenter prospective studies are still needed to validate the survival benefit of SLN mapping.

Evaluation of PUVA-Induced Skin Side Effects in Patients Referred to the Imam Reza Hospital of Mashhad in 2005-2007.

BACKGROUND: Systemic oral psoralens plus UVA therapy (PUVA) is a therapeutic method used with considerable success in many different skin disorders. PUVA therapy causes some cutaneous and noncutaneous side effects and in the present research we deal with cutaneous side effects. AIMS: Evaluation of patients to know the different skin side effects of PUVA and their importance. MATERIALS AND METHODS: All patients referred to the phototherapy unit of Imam Reza Hospital of Mashhad entered the research and skin examination was taken place initially and every 3 months thereafter. Whenever any side effect appeared, it was recorded in the information sheet. RESULTS: One hundred and twenty-eight patients were included in the research, 61 were male between 15 and 75 years and 67 were female between 10 and 61 years of age. Age of female patients at the time of cutaneous side effect appearance was less than male patients. The most common early side effect was pruritus (34.3%) and the rarest was telangiectasia (0.7%). One case of late side effect in the form of squamous cell carcinoma was observed in a patient who had received other carcinogenic drugs as well. Complications such as skin dryness, pruritus, erythema and burning sensation occurred at low doses of UVA, while dermatitis, severe limb pain and acne at moderate doses and PUVA lentigines, hypertrichosis and lichenoid lesions appeared at high doses of UVA. CONCLUSION: Considering the significant therapeutic effects and few serious side effects, PUVA therapy is a suitable and safe method for treatment of certain skin diseases.

Dermoscopic features of cutaneous leishmaniasis.

BACKGROUND: Previous studies have demonstrated that dermoscopy improves accuracy in diagnosing pigmented and non-pigmented tumors. Recently, there has been increasing evidence that dermoscopy can also be useful in the diagnosis of some skin infections. OBJECTIVE: We sought to describe the dermoscopic features of cutaneous leishmaniasis. METHOD: Dermoscopic examination (using the Derm Lite FOTO, 3Gen) of 144 CL lesions in 82 patients was performed. This study was conducted in the Imam Reza and Ghaem hospitals (Mashhad, Iran) from October 2010 to September 2011. RESULTS: We observed the following dermoscopic features: generalized erythema (81.9%), white starbursts (60.4%), yellow hue (43.8%), yellow teardrop-like structures (41.7%), central ulcers (59%), hyperkeratosis (33.3%), and milia-like cysts (4.9%). We also observed vascular structures, including dotted vessels (61.1%), hairpin vessels (37.5%), linear irregular vessels (30.6%), comma-shaped vessels (29.9%), glomerular vessels (22.9%), arborizing telangiectasia (10.4%), and corkscrew vessels (4.2%). LIMITATIONS: Biopsy and pathologic evaluation were not performed due to ethical considerations. CONCLUSION: Important vascular patterns seen in melanocytic and non-melanocytic tumors were frequently observed in this infection. Dermoscopy may be a promising tool to predict the clinical course in cases of cutaneous leishmaniasis.

Phase 2 study of the efficacy and safety of the combination of arsenic trioxide, interferon alpha, and zidovudine in newly diagnosed chronic adult T-cell leukemia/lymphoma (ATL).

Adult T-cell leukemia/lymphoma (ATL) is resistant to chemotherapy and carries a dismal prognosis particularly for the acute and lymphoma subtypes. Promising results were obtained with the combination of zidovudine and interferon-alpha. Chronic ATL has a relatively better outcome, but poor long-term survival is noted when patients are managed with a watchful-waiting policy or with chemotherapy. In ATL cell lines, arsenic trioxide shuts off constitutive NF-kappaB activation and potentiates interferon-alpha apoptotic effects through proteasomal degradation of Tax. Clinically, arsenic/interferon therapy exhibits some efficacy in refractory aggressive ATL patients. These results prompted us to investigate the efficacy and safety of the combination of arsenic, interferon-alpha, and zidovudine in 10 newly diagnosed chronic ATL patients. An impressive 100% response rate was observed including 7 complete remissions, 2 complete remissions but with more than 5% circulating atypical lymphocytes, and 1 partial response. Responses were rapid and no relapse was noted. Side effects were moderate and mostly hematologic. In conclusion, treatment of chronic ATL with arsenic, interferon-alpha, and zidovudine is feasible and exhibits an impressive response rate with moderate toxicity. Long-term follow up will clarify whether this will translate to disease cure. Overall, these clinical results strengthen the concept of oncogene-targeted cancer therapy.

Delayed complications of sulfur mustard poisoning in the skin and the immune system of Iranian veterans 16-20 years after exposure.

BACKGROUND: Extensive cutaneous burns caused by alkylating chemical warfare agent sulfur mustard (SM) have been associated with the severe suppression of the immune system in humans. We aimed to study the association between late cutaneous and immunological complications of SM poisoning. METHODS: Skin examination was performed on all SM-poisoned Iranian veterans in the province of Khorasan, Iran, who had significant clinical complications, and their SM intoxication was confirmed by toxicological analysis. Light microscopy was performed on eight skin biopsies. Blood cell counts, serum immunoglobulin and complement factor, as well as flow cytometric, analyses were performed on all the patients. The severity of cutaneous complications were classified into four grades and compared with hematological and immunological parameters, using Spearman's rank correlation test. RESULTS: Forty male subjects, confirmed with SM poisoning 16-20 years earlier, were studied. The main objective findings were hyperpigmentation (55%), dry skin (40%), multiple cherry angiomas (37.5%), atrophy (27.5%), and hypopigmentation (25%). Histopathologic findings were nonspecific and compatible with hyperpigmented old atrophic scars. Except for the hematocrit and C4 levels, hematological and immunological parameters revealed no significant correlation with the severity grades of cutaneous complications. CONCLUSION: Sulfur mustard is an alkylating agent with prolonged adverse effects on both the skin and the immune system. Although skin is a major transporting system for SM's systemic absorption, there is probably no correlation between the severity of late cutaneous and immunological complications of SM poisoning.