Marine Natural Products with Cytotoxic Properties against Epithelial Ovarian Cancer

Epithelial ovarian cancer (EOC) is a common gynecological cancer and a leading cause of death, especially because the tumors develop resistance to cisplatin. New compounds are needed to achieve better disease control and survival. We examined the cytotoxic effect of Gallic acid (GA), Hymenialdisine, and Malformin A1 (MA1) on human ovarian cancer cells. Cytotoxicity was tested using cisplatin-sensitive (A2780s) and cisplatin-resistant (A2780cp) ovarian cancer cell lines, and a normal ovarian tissue cell line (HOSE6-3) using AlamarBlue assay, Hoechst dye, and flow cytometry, and the genes and proteins of interest were assessed using western blot, and qRT-PCR. The IC50 of Hymenialdisine was 146.8 μM for A2780s cells and >300 μM for A2780cp cell lines. Both GA and MA1 decreased cell viability in a concentration-dependent manner. The IC50 of GA was 103 μM for A2780s cells, 189 μM for A2780cp cells and 262 μM for HOSE6-3 cell lines, for MA1 IC50 was 0.23 μM for A2780s and 0.34 μM for A2780cp. This was in comparison to IC50 of 31.4 μM and 76.9 μM, for A2780s cells, and A2780cp cells respectively for cisplatin. The combination of GA and MA1 with cisplatin revealed synergistic action, especially in A2780cp cell lines. The results suggest that both GA and MA1 may help overcome the resistance to cisplatin through the synergistic effect. Hence, the cytotoxic potential of GA and MA1 merit further investigation

Chemotherapy-induced non-Hodgkin\u27s lymphoma in a patient with Hodgkin\u27s disease--a case report

Modern chemotherapy and radiation treatment of Hodgkin’s disease has resulted in overall cure rates in excess of 60%1 . However, the greatly improved survival rates have also led to increasing incidence of long-term side-effects of these treatment modalities2 . The most serious consequence is the occurrence of second cancer3 . We report a case of non-Hodgkin’s lymphoma occurring in a patient who was previously treated for Hodgkin’s disease

Acute myeloid leukemia in children in Pakistan: an audit

Objective: To see the clinical features and treatment of children with Acute Myeloid Leukemia (AML) in Pakistan. Setting: Tertiary referral at a specialist Hematology/Oncology center. Methods: Retrospective, chart-based review of children (less than 14 years) admitted to the hospital with a diagnosis of AML between January 1987 and August 1997. Results: A total of 23 patients were admitted. There were 18 males and 5 females. The mean age was 8 5 years. M3 was the commonest morphological subtype (43%). Twenty- two percent of the patients presented with hyperleucocytosis (TLC\u3e 100 x i09 /L) and 95% with an elevated LDH (\u3e548 lUlL). Pneumonia at presentation was seen in 29%. Of 23 patients 14 were evaluable for responses. Six patients died early (43%); 3 before starting the chemotherapy and 3 during the induction chemotherapy, 8/11 (73%) patients entered remission. The median survival was 9 months. Conclusion: The pediatric patients with acute myeloid leukemia present with advanced disease. There is a high early death rate (within 28 days of diagnosis). The long-term outcome was inferior to that reported in the literature (JPMA 52:247; 2002)

Bacterial isolates from neutropenic febrile pediatric patients and their sensitivity patterns to antibiotics

Patients on cytotoxic therapy often develop neutropenia and fever. Our interest was to identify the common pathogens isolated from such patients and to study the sensitivity patterns of these organisms to the antibiotics used in their treatment. Thus, guidelines can be established by hospitals to identify which antibiotics can be used in the treatment of these patients when the results of cultures and sensitivities are not available. We conducted a retrospective study of neutropenic pediatrics presenting to AKUH from July, 1990 to June, 1996. A total of 153 isolates in 35 different patients were studied. Samples for culture were taken from the sites at risk. The majority of samples consisted of blood, stool, pus and urine. Twenty stool samples were also sent for microscopy. Malignancies were both hematological and non-hematological. Gram negatives were isolated in 52.9%, gram positives in 33.9% and parasites in 13.2%. Salmonella paratyphi B was the most commonly isolated organism, followed by Pseudomonas aeroginosa, Giardia lamblia was the most common parasite. Sensitivity patterns of these organisms to antibiotics studied showed that Escheria coli had the lowest sensitivity rate being only 40% sensitive to Aztreonam and 64% sensitive to Ofloxacillin. A comparison was made between our findings and those reported in literature, as well as the risk factors for developing neutropenia. A guide to management is also discussed

Epidemiological features of aplastic anaemia in Pakistan

Objective: To complete the data on the demographic features of patients diagnosed to have aplastic anemia at a single institution over a 7.5 years period. Methods: Demographic information was retrieved from the patients medical records retrospectively as well as prospectively of those patients who presented with features of aplastic anaemia. Their diagnosis was confirmed by performing a complete blood count and bone marrow trephine. Results: One hundred and forty four patients were diagnosed to have aplastic anemia; there were 106 males and 38 females. Their ages ranged from 2 to 75 years, with a median of 17 years, 112 (77.7%) patients were below the age of 30 years. Severe aplastic anemia (SAA) was seen in 74 (51.4%), very severe (VSAA) in 24 (16.7%) and non-severe aplastic anemia (NSAA) in 46(31.9%) patients. No obvious cause could be established for 74.3%. Thirteen patients admitted using drugs known to cause AA and one was a radiographer (9%). Out of 44 patients tested, 7 (15.9%) were found to have either hepatitis B virus markers or antibody to hepatitis C at the time of diagnosis of AA. However it was difficult to establish a cause and effect relationship with either drugs or viruses. Conclusion: Aplastic anaemia is found to occur mostly severe aplastic anaemia (JPMA 51:443,2001)

Induction of white cell proliferation due to haematopoietic growth factors is associated with an increase in multiple forms of dihydrofolate reductase in non-neutropenic cancer patients

Objective: Granulocyte-colony stimulating factor (G-CSF) and granulocyte macrophage-colony stimulating factor (GM-CSF) are frequently used in cancer patients to overcome the granulocytopenic effects of chemotherapy, and also to mobilize the stem cells. The mobilized stem cells are collected from the peripheral blood and used for transplantation following high doses of chemotherapy. However, the molecular mechanism by which these colony stimulating factors (CSFs) bring about proliferation of myeloid precursor cells is not clearly known. Dihydrofolate reductase (DHFR), which has an established role in DNA synthesis, could be a link between administration of CSF and stem cell proliferation. The purpose of this study was to investigate whether CSFs induce white cell proliferation by producing multiple forms of DHFR.Methods: Twelve patients with non-haematological malignancies were treated with either G-CSF or GM-CSF to mobilize stem cells. Nine healthy subjects were treated with placebo as controls. Blood samples were obtained before and after stimulation with CSFs or placebo. White blood cells were separated and concentrations of both active DHFR and immunoreactive nonfunctional form of DHFR were determined in their cytoplasm using methotrexate-binding assay and enzyme-linked immunosorbent assay, respectively. Total leucocytes count (TLC) was also monitored before and after stimulation with CSFs or placebo.Results: There was a significant (P \u3c 0.05) increase in concentration of immunoreactive nonfunctional form of DHFR and TLC following stimulation with CSFs. There was an increase in concentration of active DHFR as well, however, this did not reach statistical significance. In the placebo-treated subjects, no significant increase in active DHFR, immunoreactive nonfunctional form of enzyme or TLC was observed. However, it was noticed that the base-line values of active DHFR and immunoreactive nonfunctional form of enzyme in leucocytes of cancer patients were higher than the base-line values in leukocytes of normal healthy subjects.Conclusion: Our data suggest that colony stimulating factors induce white cell proliferation by increasing levels of multiple forms of DHFR

Increased levels of multiple forms of dihydrofolate reductase in peripheral blood leucocytes of cancer patients receiving haematopoietic colony-stimulating factors: Interim analysis

The precise mechanism whereby granulocytes proliferate when haematopoietic colony stimulating factors (CSFs) are used in neutropenic cancer patients is poorly understood. The purpose of this study was to investigate whether these cytokines bring about leucocyte proliferation by increasing the levels of multiple forms of dihydrofolate reductase (DHFR). Blood samples were collected from 36 cancer patients (25 males and 11 females) with chemotherapy-induced neutropenia. One sample of blood from each patient was obtained before therapy either with CSF, such as granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) or with placebo, and another one at the time of resolution of neutropenia. Peripheral blood leucocytes in these blood samples were counted, separated and lysed. From lysates, cytoplasmic samples were prepared and analyzed for active DHFR by a methotrexate-binding assay and for total immunoreactive DHFR by an enzyme linked immunosorbent assay. The increase in total leucocyte count (TLC) was most prominent (P \u3c 0.005) in the CSF group and less so (P \u3c 0.05) in the placebo group. The mean +/- SD concentration values of active DHFR before and after stimulation with GM-CSF found were to be 0.34 +/- 0.4 ng/mg protein and 0.99 +/- 0.82 ng/mg protein, respectively, and in the group treated with G-CSF, 0.24 +/- 0.32 ng/mg protein and 1.18 +/- 2.4 ng/mg protein, respectively. This increase in active DHFR after stimulation with CSF was statistically significant (P \u3c 0.05). Similarly, concentration values of immunoreactive but nonfunctional form of DHFR (IRE) were 110 +/- 97 ng/mg protein and 605 +/- 475 ng/mg protein before and after stimulation with GM-CSF, and 115 +/- 165 ng/mg protein and 1,054 +/- 1,095 ng/ mg protein before and after stimulation with G-CSF. This increase in concentration of IRE after stimulation with GM-CSF or G-CSF was statistically significant (P \u3c 0.005). In the control group, there was an increase in the concentration of both active DHFR and IRE after treatment with placebo. However, this was not statistically significant. Resolution of neutropenia was quicker in the groups treated with CSF compared to the control group. Results of this study indicate that colony stimulating factors (G-CSF and GM-CSF) induce white cell proliferation by increasing the levels of multiple forms of DHFR