The prevalence and predictors of herb-drug interactions among Iranian cancer patients during chemotherapy courses.

BACKGROUND: The concurrent usage of herbal medicines with conventional therapies is an important concern in cancer treatment which can lead to unexpected consequences like herb-drug interactions. This study aimed to determine the prevalence of potential herb-drug interactions and to predict factors associated with herb-drug interactions for cancer patients. METHODS: This cross-sectional study was conducted among a convenience sample of 315 cancer patients referring to the oncology clinics of Kerman city in 2018. Data were collected via comprehensive face-to-face interviews and medical chart reviews. A drug interaction checker was used to determine herb-drug interactions. The information of patients was compared based on herb-drug interactions using bivariable logistic regression models, and predictors were determined by the multivariable logistic regression model. All analyses were performed by Stata software version 16. RESULTS: Of 262 patients (83.2% of the patients) who used herbal medicines, 209 patients [79.8% (95% Confidence Intervals (CI): 75.2 - 85.1)] had potential herb-drug interactions. Chamomile was the most popular herbal medicine (n = 163, 78.0%), and minor and moderate herb-drug interactions were caused by green tea (n = 34, 16.3%) and peppermint (n = 78, 37.5%). The number of chemotherapeutic agents (OR: 1.92, 95% CI: 1.43-2.58; P-value < 0.0001) and the experienced of pain during chemotherapy courses (OR = 2.22, 95%CI:1.00-4.94; P-value = 0.04) were some of the predictors of herb-drug interactions among cancer patients. CONCLUSION: Herbal medicine use during chemotherapy was found prevalent among cancer patients; of them, the experience of potential herb-drug interactions was highly frequent. Oncologists and clinical pharmacologists are recommended to take into account challenges associated with herb-drug interactions in their routine practices, particularly during chemotherapy among these patients.

Identifying unmet information needs of advanced cancer patients in Iran: An in-depth qualitative study.

Background and Aims: One of the main vital needs for self-care in patients with advanced cancer is information need. Meeting this need has significant positive effects on improving their treatment and care. This study was conducted to identify the unmet information needs of patients with advanced cancer in Iran. Methods: This exploratory study was performed from July to February 2021 in the Kerman University of Medical Sciences cancer treatment centers. Oncologists selected eligible patients by purposeful sampling method. Semistructured and in-depth interviews were conducted with selected patients to collect data. Interviews continued until data saturation. Each interview was audio-recorded and transcribed verbatim. Results: In the interviews, 15 patients with advanced cancer ranging in age from 43 to 65 years participated. The most common type of cancer in women was breast (71.4%) and prostate (50%) in men. The two main categories of "types of unmet information needs" and "reasons for not meeting information needs" were extracted from the analysis of patient interviews, with six and four subcategories, respectively. Conclusion: Cancer patients had a large number of unmet information needs. At the time of identifying the unmet information needs of cancer patients, the basic reasons for not meeting these needs should also be considered because cultural differences and social gaps in societies are inevitable.

Reduced Expression of Natural Killer Cell-Related Activating Receptors by Peripheral Blood Mononuclear Cells from Patients with Breast Cancer and Their Improvement by Zoledronic Acid.

BACKGROUND/AIM: Natural killer (NK) cell receptors affect the NK cell-mediated elimination of malignant cells. In this experimental study the effect of Zoledronic acid (ZOL) was investigated on the expression of NK activating- (NKP46 and NKG2D) and inhibitory (KIR2DL1) receptors by Phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from breast cancer (BC) patients. MATERIALS AND METHODS: Peripheral blood mononuclear cell-extracted RNA from thirty breast cancer women and twenty-five healthy subjects was analyzed for gene expression of NKP46, NKG2D and KIR2DL1 using real time-PCR. Then, the PBMCs from BC patients were cultured in the presence of PHA with 5 µg/ml, 10 or 20 µg/ml of ZOL for 32 hours and expression of the aforementioned receptors was determined. RESULTS: Expression of NKP46, NKG2D and NKP46/KIR2DL1 ratio in BC women were lower than healthy group (P<0.01, P<0.04 and P<0.05, respectively). NKP46 expression was up-regulated by PHA-stimulated PBMCs treated with 10 µg/ml and 20 µg/ml of ZOL compared with PHA-stimulated cultures (P<0.01 and P<0.05, respectively). NKG2D expression remarkably increased by PHA-stimulated cultures treated with 5 µg/ml, 10 µg/ml and 20 µg/ml of ZOL compared with PHA-stimulated cultures (P<0.05 and P<0.02 and P<0.04, respectively). CONCLUSION: Expression of NK cell-related activating receptors decreased in BC patients. ZOL can improve the expression of NK activating receptors.

The Prevalence of Polypharmacy and Potential Drug-Drug Interactions among Iranian Cancer Patients: Which Patients were at Risk?

INTRODUCTION: Drug-Drug interactions (DDIs) are one of the considerable consequences of polypharmacy. Due to the influence of polypharmacy and drug interactions on cancer treatment and patients` health outcomes, this study aimed to determine the prevalence of polypharmacy and potential DDIs among adult cancer patients in Kerman province, southeast of Iran. METHODS: In this cross-sectional study, 315 cancer patients who referred to Kerman city oncology clinics were assessed in 2018. Data were collected through face-to-face interviews and medical charts were reviewed. Polypharmacy was defined as the use of at least five drugs simultaneously. Potential DDIs were checked using the "Drugs.com" online database. A bivariable and a multivariable logistic regression were used to determine the associated factors of outcome variables, polypharmacy status, and potential DDI in SPSS software version 23. RESULTS: Of 315 cancer patients, 191 patients (60.6%; 95% CI: 54.9, 66) used at least five drugs during chemotherapy courses. The prevalence of potential DDIs was 59.6% (n = 140, 95% confidence interval [CI]: 53.6-66.0. Experience co-morbid diseases (OR: 6.60; 95% CI: 3.82, 11.42; p value ≤ .0001), and positive metastatic status (OR: 2.80; 95% CI: 1.62, 4.82; p value ≤ .0001) could predict the polypharmacy during chemotherapy courses. Patients who suffered gastrointestinal cancers (OR: 5.55; 95% CI: 2.26, 13.62; p value ≤ .0001) and the number of prescribed or Over The Counter (OTC) drugs (OR: 1.29; 95% CI: 1.12, 1.48; p value < .0001) predicted the occurrence of potential DDIs among cancer patients. CONCLUSIONS: Regarding the high prevalence of polypharmacy and potential drug interactions among Iranian cancer patients during chemotherapy courses, it is advisable for physicians, nurses, and pharmacists to be vigilant to improve prescribing patterns. In addition, with intensive monitoring, alternative treatment strategies can be replaced.

Evaluation of anticancer, antioxidant and antibacterial properties of methanol extract of three Acantholimon Boiss. species.

OBJECTIVE: Acantholimon is a genus of perennial plant within the Plumbaginaceae family. Here, we aimed to investigate anticancer, antioxidant, and antibacterial potential of methanol extract of three Iranian endemic species of Acantholimon including A. austro-iranicum, A. serotinum and A. chlorostegium. MATERIALS AND METHODS: MTT assay was used to evaluate the in vitro cytotoxicity and apoptosis induction was examined by annexin V-PE apoptosis detection kit. Antioxidant activity was reported based on the DPPH-scavenging and DCF-DA assay. Antibacterial activity was measured by disc diffusion and micro-well dilution assay. RESULTS: MTT assay showed less cytotoxicity of methanol extracts against the HUVEC normal cell line (IC50 values: 817-900 µg/ml) compared to cancer cell lines MCF-7, HT29, SH-SY5Y, NCCIT and A549 (IC50 values: 213 to 600 µg/ml) that show the specificity of extracts toward cancer cells. Plant extract showed apoptosis induction and cell cycle arrest at the G0/G1 phases documented by annexin V staining and flow cytometry. According to antioxidant tests, extracts exhibited significant DPPH scavenging potential (IC50 values: 30-37 µg/ml) and could protect against H2O2-induced oxidative stress. Antibacterial activities showed a stronger inhibitory effect on Escherichia coli and Pseudomonas aeruginosa as Gram- negative bacteria (diameter of inhibition zone: 11-13 mm and minimal inhibition concentration (MIC): 3.175 to 12.5 mg/ml) compared to Gram-positive bacteria including Enterococcus faecalis and Staphylococcus aureus (diameter of inhibition zone: 3-7 mm and MIC: 25 to 50 mg/ml). CONCLUSION: Our results suggested moderate cytotoxic and antibacterial potential and noteworthy antioxidant activity for the examined Acantholimon species.

Copper and Zinc Levels in Myelodysplastic Syndrome Patients versus Healthy Subjects.

BACKGROUND: Myelodysplastic syndrome (MDS) is a heterogeneous hematological disease and certain serum factors are assumed to be involved in its pathogenesis and progression. Given this, our aim was to comparatively investigate the copper, zinc, and iron levels in MDS patients and healthy individuals. METHODS: This case-control study was conducted on 31 patients with MDS (according to the WHO criteria after investigating laboratory tests such as peripheral blood smear and bone marrow aspiration) attending Bahonar Hospital, Kerman, Iran, and 31 healthy subjects from 2016 to 2018. The levels of copper, ceruloplasmin, zinc, ferritin, and iron were compared between the two groups. RESULTS: Among the MDS patients, five individuals (16.13%) had low serum copper level (mean: 67.8 ± 4.35 µg/dl). Serum copper level was 111.3 ± 27.7 and 138.3 ± 26.6 in case and control groups, respectively (P = 0.0001). The serum zinc level and bone marrow iron level were also significantly different between the two groups (P < 0.05). CONCLUSION: Overall, it can be concluded that because only a small proportion of the MDS patients enrolled in this study were found to have lower copper levels compared with the MDS patients population, further studies with a larger sample size and also clinical trials in MDS patients with serum zinc, and copper deficiency are recommended, and post-treatment hematological reassessment would also be beneficial to achieving more definitive results.

Prevalence and Molecular Subtyping of Blastocystis from Patients with Irritable Bowel Syndrome, Inflammatory Bowel Disease and Chronic Urticaria in Iran.

BACKGROUND: Blastocystis is a parasite that colonizes in the human intestine. Its clinical features include diarrhea, abdominal pain, or urticarial and irritable bowel syndrome (IBS). Spite of being significant genetic diversity and numerous subtypes within the genus there were no associations between its subtypes and symptomatology. MATERIALS AND METHODS: Aim of this project was subtyping of the protozoa in 184 Iranian people with history of IBS/IBD (n = 74) or chronic urticaria (n = 59) and individuals referred to general clinic (n = 51). Microscopic and molecular examinations used for identifying and subtyping of Blastocystis. RESULTS: Overall, frequency of the parasite was 24.46% while, 29.41% of people who referred to general clinic, 20.27%, and 25.42% of IBS/IBD and urticarial cases were infected, respectively. Subtyping result showed that 28.89% of all people were infected with Blastocystis sp. while the prevalence of ST3, ST2 and ST1 were 22.22%, 22.22%, and 17.78%, respectively. Blastocystis sp., was identified in most IBS/IBD cases (46.7%) followed with ST2 and ST3 (13.3 and 13.3, respectively). Whereas, in chronic urticaria group ST2(33.3%) was the major subtype and most individuals in control group were infected with ST3 (33.3%). Pearson's Chi Square test showed no significant differences between the parasite or subtype prevalence and diseases (p > 0.05). CONCLUSION: Given significant factors have effect on clinical signs including host or parasite genetics, microbiota, as well as environmental factors, it seems that further studies are needed to find out different markers of host susceptibility to diverse parasite genotypes in patients with irritable bowel syndrome or urticaria.

Mast Cell Leukemia with Ascites and Multiple Organs Damage.

Mast Cell Leukemia (MCL), a rare subtype of systemic mastocytosis is defined by bone marrow involvement as atypical and aleukemic mast cells, if more than 20% and less than 10% of peripheral WBCs are mast cells, respectively. We met a case of aleukemic MCL presenting with anemia and ascites for 2 years, referred for BM evaluation, suspicious of leukemia. Our findings included BM involvement by diffused aggregates of oval- and spindle-shaped atypical mast cells, lacking mature mast cells and other hematopoietic cells. The mast cells were absent in peripheral blood smear. Further assessments showed positive reaction of mast cells metachromatic granules with Tryptase, Giemsa and Toluidine blue stains, the expression of CD117/KIT and CD45 by immunohistochemistery, and elevated level of serum Tryptase. Radiologic investigations revealed generalized lymphadenopathy, and massive hepatosplenomegaly, followed by the cervical lymphadenectomy, and liver wedge biopsy. Suspicious peritoneal lesions were identified and underwent excisional biopsy. Microscopic evaluations showed lymph nodes and liver involvement by cancer cells and the same features in peritoneal seeding. Multiple organs damage progressed in few months and the patient died despite surgery and chemotherapy. In conclusion, we report an extremely rare case of aleukemic MCL with multiple organs damage such as liver, peritoneum, spleen, gastrointestinal tract and BM, presenting by ascites. According to this case and previous parallel studies, we suggest some clinicopathologic features in favor of poor prognosis, including the presence of multiple organs damage, hepatomegaly, ascites, peritoneal seeding, the absence of mature mast cells and other hematopoietic cells in the BM, and elevated serum Tryptase level.

Hemo-Lymphopoietic Malignancies Surround the Women of the Family: A Case Report and Literature Review.

The co-occurrence of different types of hemo-lymphopoietic malignancies within a family provides clues about the pattern of inheritance and common environmental risk factors. A family presented with developing hemo-lymphopoietic cancers in three female first-degree relatives: a mother and her daughters. Case 1 was diagnosed with Walden Strom's macroglobulinemia at age 57. Case 2 and 3 presented with chronic myelogenous leukemia at age 32 and diffuse large B-cell lymphoma at age 28, respectively. There were not any significant common environmental risk factors in this family, but all three cases suffered from skin dermatitis and one of them, who suffered from chronic myelogenous leukemia, was diagnosed with morphea. This family had a sedentary and stressful lifestyle. Genetic is the foundation of some familial aggregation of cancers. Common lifestyle habits and environmental etiologies are important. Morphea as an autoimmune disease could have the essential role in developing hematolymphoid malignancies.

Prognostic Significance of Reduction in Ki67 Index After Neoadjuvant Chemotherapy in Patients With Breast Cancer in Kerman Between 2009 And 2014.

BACKGROUND AND OBJECTIVE: Breast cancer is the most common malignancy among women. The Neoadjuvant chemotherapy is the treatment of choice for non-operable tumors. The Ki67 is a proliferation marker that can be used to predict the therapeutic response to chemotherapy and the patients' prognosis. METHODS: This retrospective study was carried out on 55 consecutive patients with breast cancer referred to a Training Tertiary Healthcare Center in Kerman, Iran since 2009 to 2014. After diagnostic approval, the tissue samples of patients were examined for estrogen and progesterone receptors, ki67 and HER2-neu markers by using immunohistochemical staining. Then the patients were treated with 6 cycles of Neoadjuvant chemotherapy regimens by Doxorubicin and Taxans or 4 chemotherapy cycles, containing Anthracycline and Cyclophosphamide and 4 cycles of Paclitaxel. After mastectomy, their samples were reexamined for ki67 again and classified into three groups (low: ki67<15%), medium (Ki67 = 16-30%) and high (Ki67> 30%). RESULTS: Before chemotherapy, 54.5% of the patients had high expression of Ki67. But after chemotherapy, 52.7 of the patients had complete therapeutic response showing that the Ki67 level was reduced significantly (P=0.003). CONCLUSION: Before and after Neoadjuvant chemotherapy, Ki67 measurements may be used as a predictive marker of therapeutic response.

Stool antigen immunodetection for diagnosis of Giardia duodenalis infection in human subjects with HIV and cancer.

Human infection with the protozoan parasite Giardia duodenalis is one the most common parasitic diseases worldwide. Higher incidence rates of giardiasis have been reported from human subjects with multiple debilitating chronic conditions, including hypogammaglobulinemia and common variable immunodeficiency (CVID). In the current study, stool specimens were collected from 199 individuals diagnosed with HIV or cancer and immunocompetent subjects. The sensitivity of microscopy-based detection on fresh stool preparations, trichrome staining and stool antigen immunodetection for the diagnosis of G. duodenalis were 36%, 45.5% and 100%, respectively when compared with a highly sensitive stool-based PCR method as the gold standard. Further multilocus molecular analyses using glutamate dehydrogenase (gdh) and triose phosphate isomerase (tpi) loci demonstrated that the AI genotype of G. duodenalis was the most prevalent, followed by the AII genotype and mixed (AI+B) infections. We concluded that stool antigen immunodetection-based immunoassays and stool-based PCR amplification had comparable sensitivity and specificity for the diagnosis of G. duodenalis infections in these populations. Stool antigen detection-based diagnostic modalities are rapid and accurate and may offer alternatives to conventional microscopy and PCR-based diagnostic methods for the diagnosis of G. duodenalis in human subjects living with HIV or cancer.

Metastasis and its Related Factors in Female Breast Cancer Patients in Kerman, Iran

Background: Metastasis is important in survival and the quality of life of female breast cancer patients. This study was run in order to investigate metastasis and its related factors in female breast cancer patients in Kerman province from 2005 to 2015. The aim of this study was to investigate the factors associated with secondary metastasis in female breast cancer patients in the largest province of Iran (Kerman). Materials and Methods: In this case-control study, medical records of women diagnosed with breast cancer between the years of 2005 to 2015 were studied. Among them, 200 breast cancer patients with secondary metastasis were randomly selected as cases and 400 patients without metastasis were selected as the control group. Backward logistic regression, chi-square test, t-test and Mann-Whitney-U test were performed for comparing the two groups in SPSS 22. Results: Disease stage at diagnosis was significantly associated with secondary metastasis (p<0.001). Female patients with stage III breast cancer at the time of diagnosis had a higher chance OR=9.11 (CI 95%=2.99-27.76) of metastasis than women with stage 0 and 1 at diagnosis. Also, patients from rural areas had a higher chance for metastasis OR=1.89 (CI 95%=1.04-3.41). Other factors such as age, tumor size, tumor grade at diagnosis, hormone receptor status of estrogen and progesterone and Her-2 showed no significant association with metastasis (p>0.05). Conclusion: Stage at diagnosis and the residential location of patients were the most important factors related to secondary metastasis. These results emphasize the importance of early diagnosis, adequate education and awareness for breast cancer screening.

Comparative pharmacokinetic evaluation and bioequivalence study of three different formulations of Imatinib Mesylate in CML patients.

BACKGROUND: Imatinib is known as the drug of choice for treatment of chronic myeloid leukemia (CML). For adults the recommended daily dosage of 400 mg requires simultaneous intake of up to four capsules or tablets each 100 mg. A new 400 mg film coated tablet developed due to the need to swallow multiple capsules or tablets per dose and that was a negative impact on treatment adherence. SUBJECTS AND METHODS: A group of 36 patients were randomly assigned to receive Imatinib as 4×100 mg capsules, 4×100 mg tablets and 1×400 mg tablet. Blood sampling was performed for up to 48 h after first dosing. After that, subjects were monitored to assess drug related adverse events. Pharmacokinetic parameters were assessed using concentration-time curves for plasma Imatinib and its metabolite. RESULTS: Mean area under the curve (AUC (0-∞)) values were 27011, 25811 and 25699 ng/ml for 4×100 mg capsules, 4×100 mg tablets and 1×400 mg tablets, respectively. Cmax values were 1548, 1605 and 1622 ng/ml and t1/2 values were 15.7, 15.8 and 15.6 h. The Test/Reference ratios for AUC (0-∞), AUC (0-48), and Cmax were 0.99, 0.99 and 1.02 for 4×100 mg tablets versus 4×100 mg capsules and 0.96, 0.96 and 0.99 for 1×400 mg tablet versus 4×100 mg capsules. The 95% confidence intervals were fully contained within the accepted interval. The mild and moderate adverse events considered to be drug related were reported. These events showed no clustering by type of dosage form and were of little to no clinical significance. CONCLUSION: Film coated (400 mg) tablet dosage formulations of Imatinib is bioequivalent to the commercial available 100 mg hard gelatin capsule, and is as safe and well tolerated.

The Intricate Expression of CC Chemokines in Glial Tumors: Evidence for Involvement of CCL2 and CCL5 but Not CCL11.

Chemokines are biologically active peptides involved in the pathogenesis of various pathologies including brain malignancies. They are amongst primitive regulators of the development of immune responses against malignant glial tumors. The present study aimed to examine the expression of CC chemokines in anaplastic astrocytoma and glioblastoma multiform patients at both mRNA and protein levels. Blood specimens in parallel with stereotactic biopsy specimens were obtained from 123 patients suffering from glial tumors and 100 healthy participants as a control. The serum levels of CCL2, CCL5, and CCL11 were measured by ELISA and stereotactic samples subjected to western and northern blotting methods for protein and mRNA, respectively. Demographic characteristics were also collected by a researcher-designed questionnaire. Results of the present study indicated that, however,CCL2 and CCL5 are elevated in serum and tumor tissues of patients suffering from a glial tumor at both mRNA and protein levels, the CCL11 was almost undetectable. According to the findings of the present investigation, it could presumably be reasonable to conclude that chemokines are good predictive molecules for expecting disease severity, metastasis, and response to treatment.

BRCA1 Gene Mutations in Breast Cancer Patients from Kerman Province, Iran.

BACKGROUND: Breast cancer is the most common malignancy in Iranian women. Mutations in BRCA1 gene is one of the important genetic predisposing factors in breast cancer. This gene is a tumor suppressor that plays an important role in regulating the functions of RAD51 protein for strand invasion in homologous recombination repair. METHODS: The BRCA1 gene has amplified in the DNA isolated from breast cancer patients' leukocytes, using Polymerase Chain Reaction technique. The PCR products have sequenced using an automated DNA sequencer and subsequently obtained data have aligned with the human BRCA1 DNA sequences available online. RESULTS: In this study, we have considered nine different mutations on 60 examined chromosomes from 30 patients, living in Kerman province. A deletion of one adenine (c.1017delA) and insertion of one cytosine (c.969InsC) have found as the most frequent (20%) mutation in this survey. A substitution of thymine for adenine (c.999T>A) has detected as the second common BRCA1 gene defect (6.7%). The other mutations have identified as single nucleotide replacement including: c.792A>C, c.825G>C, c.822T>A, c.1068A>G, c.969A>T and c.966T>C. CONCLUSION: The identified BRCA1 mutations were in accordance with the previous reports. To our knowledge, four mutations: (c.969InsC, c.792A>C, c.825G>C, c.822T>A) which have identified in this study, have not been previously reported in the literature. A larger cohort study would help identifying all relevant BRCA1 mutations in this population.