interleukin-8 and Carcinoma-in-Situ

We determined whether the proinflammatory cytokine interleukin-8 (IL-8) can serve as a predictor for the response to standard (120 mg.) and low (40 mg.) dose intravesical bacillus Calmette-Guerin (BCG) (modified Danish 1331 strain) for managing superficial bladder cancer in patients at risk for recurrence and progression.. We randomized 26 patients with superficial bladder cancer to receive a 6-week course of standard dose 120 mg. or low dose 40 mg. intravesical BCG. Voided urine samples were collected immediately before and after (2 and 4 hours) BCG instillation. Urine samples were centrifuged at 1,500 rpm for 8 minutes and stored at -80C. IL-8 was measured using a commercial enzyme-linked immunosorbent assay. Patients were monitored for recurrence, progression and side effects of BCG treatment at 3-month intervals.. At a median followup of 24 months (range 12 to 30), 5 and 6 patients who received a standard and low dose, respectively had disease recurrence and/or progression (nonresponders). At 4 hours after BCG mean Il-8 levels plus or minus SD were significantly higher in responders than in nonresponders (1,099.33 +/- 708.51 versus 261.82 +/- 182.66 pg./ml., p = 0.001). There was no difference at 4 hours in mean IL-8 levels in the standard and low dose groups (596.92 +/- 546 and 893 +/- 798.67 pg./ml., respectively, p = 0.28). In all patients who remained disease-free IL-8 levels were greater than 400 pg./ml. In 9 of the 11 patients with disease recurrence/progression IL-8 levels were less than 400 pg./ml.. IL-8 secretion after the initial intravesical BCG instillation strongly correlates with the possibility of future recurrence/progression. The quantitative IL-8 response to low and standard dose intravesical BCG (Danish 1331) is similar.

Topics: BCG Vaccine; Carcinoma in Situ; Disease Progression; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; India; Interleukin-8; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Precancerous Conditions; Prospective Studies; Treatment Outcome; Urinary Bladder; Urinary Bladder Neoplasms

We analysed local cellular and humoral immunity factors in the anal mucosa in an attempt to explain how HIV infection increases the risk of anal cancer in HPV-infected patients.. HIV-positive cases and matched HIV-negative controls with more than one recurrence of condylomas were included in a prospective study following treatment of the initial lesions. Patients were followed every 3 to 6 months for the development of anal intraepithelial neoplasia (AIN3) and cancer for up to 60 months. Tissue CD1a(+), CD3(+), CD4(+), CD8(+) cells and mRNAs of selected cytokines and chemokines were quantified and compared in patients with or without AIN3 or cancer using morphometric or immunohistochemistry analysis and qRT-PCR.. Sixty-six individuals (22 patients and 44 controls) were included. In the case group, CD1a(+) and CD3(+) cell counts were significantly lower in biopsies from AIN3 and cancer specimens compared with those from AIN 1-2 or normal biopsies (P < 0.0001). A CD1a(+) count of < 10/mm was predictive of AIN3 and cancer (Odds ratio = 9.4, 95% CI: 5.4-18.3, P < 0.0001). IL-8 and IL23 levels were significantly higher in cancer than in non-cancer tissues regardless of HIV status (P = 0.02). FoxP3 expression was significantly higher in HIV-infected cases than in controls with AIN3/cancer (P < 0.04).. Depletion of CD1a(+) and CD3(+) cells and overexpression of FoxP3 in the anal mucosa appear likely to contribute to the risk of HPV-related anal cancer in HIV-infected patients. Furthermore, overexpression of IL-8 and IL-23 in the anal mucosa might be responsible for the development of this cancer regardless of HIV status.

Topics: Adult; Anal Canal; Antigens, CD1; Anus Neoplasms; Carcinoma in Situ; CD3 Complex; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Female; Forkhead Transcription Factors; HIV Infections; Humans; Interleukin-23; Interleukin-8; Lymphocyte Count; Male; Papillomavirus Infections; Regression Analysis; Risk Factors; RNA, Messenger

Interleukin (IL)-8 is one of several angiogenic factors produced in bladder cancer cell lines. Although many studies have indicated that IL-8 is increased in infectious/inflammatory processes, elevated levels of IL-8 in urine also may be indicative of active transitional cell carcinoma (TCC).. Urinary IL-8 levels were measured with an enzyme-linked immunosorbent assay in subjects with TCC (n = 51), prostate cancer (n = 17), or a history of successfully treated TCC (n = 23) and in healthy subjects (n = 49). In addition, urinary IL-8 levels were measured in 21 subjects before, during, and 1 month after intravesical therapy with bacille Calmette-Guérin or mitomycin C.. The median urinary IL-8 levels were greater in subjects with TCC (64 pg/mL urine) than in healthy subjects (6 pg/mL urine), subjects with prostate cancer (0.5 pg/mL urine), or subjects with a history of successfully treated TCC (5.0 pg/mL urine). Urinary IL-8 levels were greater in subjects with invasive (high-stage) TCC than in those with low-stage TCC. Furthermore, the postintravesical instillation levels of urinary IL-8 levels were greater in patients whose TCC recurred compared with those whose TCC was in remission.. IL-8 levels were greater in subjects with TCC compared with those with successfully treated TCC. IL-8 levels increased with TCC stage, indicating that they are greater in more invasive (ie, angiogenic) tumors. A reduction in urinary IL-8 levels after treatment with bacille Calmette-Guérin or mitomycin C may reflect a decrease in bladder cancer cells and/or in other cells that produce IL-8.

Topics: Adenocarcinoma; Administration, Intravesical; Aged; Antineoplastic Agents, Alkylating; BCG Vaccine; Biomarkers, Tumor; Carcinoma in Situ; Carcinoma, Transitional Cell; Female; Humans; Immunotherapy; Interleukin-8; Male; Middle Aged; Mitomycin; Prospective Studies; Prostatic Neoplasms; Urinary Bladder Neoplasms