Opium use and risk of colorectal cancer: a multi-center case-referent study in Iran.

BACKGROUND: Opium use has been associated with an increased risk of cancers of the lung, oesophagus, and pancreas, and it was recently classified by the International Agency for Cancer Research as carcinogenic to humans. It is not clear whether opium also increases the risk of colorectal cancer (CRC). The aim of our study was to assess the association between various metrics of opium use and the risk of CRC. METHODS: This case-referent study from seven provinces in Iran comprised 848 CRC cases and 3215 referents. Data on opium use (duration, amount, frequency) and potential confounders were collected by trained interviewers. Multivariable unconditional logistic regression models were used to measure odds ratios (OR) adjusted for age, gender, province, marital status, family history of CRC-linked cancers, consumption of red meat, fruits and vegetables, body shape, occupational physical activity, and socioeconomic status. RESULTS: Regular opium consumption was not associated with the risk of CRC (OR 0.9, 95% confidence interval, CI: 0.7, 1.2) compared to subjects who never used opium. However, frequent opium use more than twice a day was associated with an increased risk of CRC compared to non-users of opium (OR: 2.0, 95% CI: 1.1, 3.8; p for quadratic trend 0.008). CONCLUSION: There seems to be no overall association between opium use and CRC, but the risk of CRC might be increased among persons who use opium many times a day.

Opium use and risk of lung cancer: A multicenter case-control study in Iran.

Opium use was recently classified as a human carcinogen for lung cancer by the International Agency for Research on Cancer. We conducted a large, multicenter case-control study evaluating the association between opium use and the risk of lung cancer. We recruited 627 cases and 3477 controls from May 2017 to July 2020. We used unconditional logistic regression analyses to estimate the odds ratios (OR) and 95% confidence intervals (CI) and measured the association between opium use and the risk of lung cancer. The ORs were adjusted for the residential place, age, gender, socioeconomic status, cigarettes, and water pipe smoking. We found a 3.6-fold risk of lung cancer for regular opium users compared to never users (95% CI: 2.9, 4.6). There was a strong dose-response association between a cumulative count of opium use and lung cancer risk. The OR for regular opium use was higher for small cell carcinoma than in other histology (8.3, 95% CI: 4.8, 14.4). The OR of developing lung cancer among opium users was higher in females (7.4, 95% CI: 3.8, 14.5) than in males (3.3, 95% CI: 2.6, 4.2). The OR for users of both opium and tobacco was 13.4 (95% CI: 10.2, 17.7) compared to nonusers of anything. The risk of developing lung cancer is higher in regular opium users, and these results strengthen the conclusions on the carcinogenicity of opium. The association is stronger for small cell carcinoma cases than in other histology.

Opium use and risk of bladder cancer: a multi-centre case-referent study in Iran.

BACKGROUND: Bladder cancer (BC) is the 10th most common type of cancer worldwide and the fourth most common type of cancer in Iran. Opium use is considered as one of the risk factors for BC. We aim to assess the association between various parameters of opium use, which in Iran is mainly ingested or smoked in various forms, and the risk of BC. METHOD: In this multi-centre case-referent study in Iran, 717 BC cases and 3477 referents were recruited to the study from May 2017 until July 2020. Detailed histories of opium use (duration, amount, frequency) and potential confounders were collected by trained interviewers. Multivariable unconditional logistic regression models were used to measure adjusted odds ratio (OR) and 95% confidence intervals (CI). The ORs were adjusted for age, gender, place of residence and pack-years of cigarette smoking. RESULTS: Regular opium consumption was associated with an increased risk of BC (OR 3.5, 95% CI: 2.8, 4.3) compared with subjects who never used opium. Compared with continuous users, the risk decreased to one-third for those who stopped opium more than 10 years ago. The adjusted OR for those who used both crude opium (teriak) and opium juice was 7.4 (95% CI: 4.1, 13.3). There was a joint effect of opium and tobacco (OR for users of both opium and tobacco 7.7, 95% CI: 6.0, 9.7). CONCLUSIONS: Regular opium use is associated with an approximately 4-fold risk for BC. The OR decreases along with the increasing time since stopping opium use.

Therapeutic potential of novel formulated forms of curcumin in the treatment of breast cancer by the targeting of cellular and physiological dysregulated pathways.

Breast cancer is among the most important causes of cancer related death in women. There is a need for novel agents for targeting key signaling pathways to either improve the efficacy of the current therapy, or reduce toxicity. There is some evidence that curcumin may have antitumor activity in breast cancer. Several clinical trials have investigated its activity in patients with breast cancer, including a recent trial in breast cancer patients receiving radiotherapy, in whom it was shown that curcumin reduced the severity of radiation dermatitis, although it is associated with low bioavailability. Several approaches have been developed to increase its absorption rate (e.g., nano crystals, liposomes, polymers, and micelles) and co-delivery of curcumin with adjuvants as well as different conjugation to enhance its bioavailability. In particular, micro-emulsions is an option for transdermal curcumin delivery, which has been reported to increase its absorption. Lipid-based nano-micelles is another approach to enhance curcumin absorption via gastrointestinal tract, while polymer-based nano-formulations (e.g., poly D, L-lactic-co-glycolic [PLGA]) allows the release of curcumin at a sustained level. This review summarizes the current data of the therapeutic potential of novel formulations of curcumin with particular emphasis on recent preclinical and clinical studies in the treatment of breast cancer.

Therapeutic Potential of Curcumin in Treatment of Pancreatic Cancer: Current Status and Future Perspectives.

Pancreatic cancer is among the leading cause of deaths due to cancer with extremely poor prognosis. Gemcitabine is being used in the treatment of patient with pancreatic ductal adenocarcinoma (PDAC), although, the response rate is bellow 12%. A recent phase III trial revealed that FOLFIRINOX could be an option for the treatment of metastatic PDAC patients, although it is associated with increased toxicity. Therefore, identification of novel agents that either improves gemcitabine activity, within novel combinatorial approaches, or with a better efficacy than gemcitabine is warranted. The antitumor activity of curcumin in several tumors, including prostate, breast and colorectal cancers have investigated. A recent phase II trial explored the effects of curcumin in advanced pancreatic cancer patient. They found that oral curcumin was well tolerated. Another trial showed the activity of 8,000 mg of curcumin in combination with gemcitabine in patients with advanced pancreatic cancer. This review summarizes the current knowledge about possible molecular mechanisms of curcumin in PDAC with particular emphasis on preclinical/clinical studies in pancreatic cancer treatment. J. Cell. Biochem. 118: 1634-1638, 2017. © 2017 Wiley Periodicals, Inc.

Therapeutic Potential of Targeting Wnt/ß-Catenin Pathway in Treatment of Colorectal Cancer: Rational and Progress.

Wnt/ß-catenin pathway is one of the main/frequent dysregulated pathways in several tumor types, including colon cancer. Aberrant activation of this pathway is associated with cell proliferation, invasive behaviors, and cell resistance, suggesting its potential value as a therapeutic target in treatment of CRC. Several agents have been developed for targeting of this pathway (e.g, natural agents: curcumin, 3,3-diindolylmethane, phytoestrogen; Synthetic/small Wnt inhibitors: Rofecoxib; PRI-724, CWP232291; and monoclonal antibody against frizzled receptors, Vanituctumab). This review summarizes the current knowledge about the therapeutic potential of targeting Wnt pathway with particular emphasis on preclinical/clinical studies in treatment of colorectal cancer. J. Cell. Biochem. 118: 1979-1983, 2017. © 2017 Wiley Periodicals, Inc.

The Results of Chemotherapy with Two Variants of Intravenous CMF in Patients with Early Stage Breast Carcinoma; Does Dose Density Matter?

No direct comparisons can be made in early stages of breast cancer, between the intravenous combinations of: cyclophosphamide, methotrexate, and fluorouracil; named modified versions of CMF with the classical oral version of CMF. Since these modifications have different dose intensities and densities, the outcomes for their subsequent treatments may be varied, and not produce the same results. Despite that, classical CMF has been commonly replaced with intravenous modifications. This study aimed to assess the results of treatment with two common intravenous modification of CMF chemotherapy; to represent the most effective and successful substitute of classical CMF. Five hundred patients in two groups were eligible to take part in the experiment. For two hundred and twenty-nine patients in the group CMF 1&8, chemotherapy was administered intravenously on days 1 and 8 every 28 days for six cycles consisting of: cyclophosphamide 600 mg/m2 , methotrexate 40 mg/m2 , fluorouracil 600 mg/m2 . In the group CMF 1 which consisted of 271 patients, chemotherapy was administered with all the same drugs and doses, however, it was only administered on day 1 and repeated at 21-day intervals for six cycles. Overall survival (OS), disease-free survival (DFS), the prognostic factors and other probable interventional factors were then compared between the two groups. The 5-year OS rate of 87.5% and 10-year OS rate of 82% in the group CMF 1&8 were statistically significantly better than 5-year OS of 84% and 10-year OS of 61.5% in the group CMF 1 (p = 0.01). The 5-year and 10-year DFS rates were 76% and 60% respectively, in the group CMF 1&8 compared with 77% and 54% respectively in the group CMF 1 (p = 0.8). Two groups were comparable regarding their distribution of different prognostic factors and other probable interventional factors. Considering 30% higher dose density of drugs in the protocol of CMF 1&8, the improving outcome can be related to the efficacy of dose-dense chemotherapy. Therefore, this intravenous modification is the better substitute of classical CMF.

Nevasic audio program for the prevention of chemotherapy induced nausea and vomiting: A feasibility study using a randomized controlled trial design.

PURPOSE: Pharmacological therapy is only partially effective in preventing or treating chemotherapy induced nausea and vomiting (CINV). Therefore, exploring the complementary role of non-pharmacological approaches used in addition to pharmacological agents is important. Nevasic uses specially constructed audio signals hypothesized to generate an antiemetic reaction. The aim of this study was to examine the feasibility of conducting a randomized controlled trial (RCT) to evaluate the effectiveness of Nevasic to control CINV. METHODS: A mixed methods design incorporating an RCT and focus group interviews. For the RCT, female breast cancer patients were randomized to receive either Nevasic plus usual care, music plus usual care, or usual care only. Data were analysed using descriptive statistics and linear mixed-effects models. Five focus group interviews were conducted to obtain participants' views regarding the acceptability of the interventions in the trial. RESULTS: 99 participants were recruited to the RCT and 15 participated in focus group interviews. Recruitment targets were achieved. Issues of Nevasic acceptability were highlighted as weaknesses of the program. This study did not detect any evidence for the effectiveness of Nevasic; however, the results showed statistically significant less use of anti-emetics (p = 0.003) and borderline non-significant improvement in quality of life (p = 0.06). CONCLUSIONS: Conducting a non-pharmacological intervention using such an audio program is feasible, although difficulties and limitations exist with its use. Further studies are required to investigate the effectiveness of Nevasic from perspectives such as anti-emetic use, as well as its overall effect on the levels of nausea and vomiting.