Types Of Cancer Chemotherapy Research Articles

Nab-paclitaxel interrupts cancer-stromal interaction through C-X-C motif chemokine 10-mediated interleukin-6 downregulation in vitro.

Cancer‐associated fibroblasts (CAF), derived from stroma of cancer tissues, interact with cancer cells and play an important role in cancer initiation, growth, and metastasis. Nab‐paclitaxel (nab‐PTX) is a 130 nm albumin‐binding paclitaxel and recommended for many types of cancer chemotherapy. The nab‐PTX stromal‐disrupting effect during pancreatic cancer treatment has been reported. The aim of the present study was to determine the role of nab‐PTX in cancer cells and CAF interaction. Cancer cells (MIA PaCa‐2 and Panc‐1) were cocultured with CAF or treated with CAF conditioned medium, after which their migration and invasion ability, epithelial‐mesenchymal transition (EMT)‐related marker expression and C‐X‐C motif chemokine 10 (CXCL10) expression and secretion were detected. Nab‐PTX treatment was carried out during the coculture system or during preparation of CAF conditioned medium. Then cancer cell migration and invasion ability, EMT‐related marker expression, CXCL10 expression and secretion, and interleukin‐6 (IL‐6) expression and secretion by CAF were checked After coculture with CAF, migration and invasion ability of cancer cells increased. CAF also downregulated E‐cadherin and upregulated N‐cadherin and vimentin expression in cancer cells. During coculture or stimulation with cancer cell‐cultured medium, CAF significantly increased IL‐6 expression and secretion. However, nab‐PTX in the coculture system canceled CAF‐induced migration and invasion promotion and EMT‐related gene changes. Moreover, nab‐PTX increased CXCL10 expression of cancer cells which blocked CAF IL‐6 expression and secretion. Nab‐PTX treatment could increase CXCL10 expression of cancer cells which blocks CAF cancer cell migration and invasion‐promoting effect by inhibiting IL‐6 expression.

Apoptosis and Cancer

Cancer is a disease involving the abnormal accumulation of cells resulting from an imbalance of proliferation and programmed cell death. This review focuses on the mitochondrial apoptotic pathway, a mechanism of programmed cell death with particular relevance to cancer. Starting over 30 years ago, basic findings in model organisms have been combined with findings in clinical cytogenetics to uncover a family of proteins, the BCL-2 family, that regulates the commitment to apoptosis by controlling permeabilization of the mitochondrial outer membrane. Cancer cells are generally more poised to engage the apoptotic machinery than normal cells are, a fact that likely underlies much of the therapeutic index exploited by many types of cancer chemotherapy. More recently, small molecules directly targeting the antiapoptotic proteins of the BCL-2 family have entered the clinic for testing in cancer. One therapeutic, venetoclax (ABT-199), has recently gained FDA approval in a landmark achievement for the apoptosis community. Important future efforts will be directed at building combinations of agents that selectively induce apoptosis in cancer cells.

In vivo oxidative metabolism of a major peroxidation-derived DNA adduct, M1dG.

3-(2-Deoxy-beta-D-erythro-pentofuranosyl)pyrimido[1,2-alpha]purin-10(3H)-one (M1dG) is a DNA adduct arising from the reaction of 2-deoxyguanosine with the lipid peroxidation product, malondialdehyde, or the DNA peroxidation product, base propenal. M1dG is mutagenic in bacteria and mammalian cells and is present in the genomic DNA of healthy human beings. It is also detectable, albeit at low levels, in the urine of healthy individuals, which may make it a useful biomarker of DNA damage linked to oxidative stress. We investigated the possibility that the low urinary levels of M1dG reflect metabolic conversion to derivatives. M1dG was rapidly removed from plasma (t(1/2) = 10 min) after i.v. administration to rats. A single urinary metabolite was detected that was identified as 6-oxo-M1dG by MS, NMR spectroscopy, and independent chemical synthesis. 6-Oxo-M1dG was generated in vitro by incubation of M1dG with rat liver cytosols, and studies with inhibitors suggested that xanthine oxidase and aldehyde oxidase are involved in the oxidative metabolism. M1dG also was metabolized by three separate human liver cytosol preparations, indicating 6-oxo-M1dG is a likely metabolite in humans. This represents a report of the oxidative metabolism of an endogenous DNA adduct and raises the possibility that other endogenous DNA adducts are metabolized by oxidative pathways. 6-Oxo-M1dG may be a useful biomarker of endogenous DNA damage associated with inflammation, oxidative stress, and certain types of cancer chemotherapy.

An adenoviral system for tetracycline‐regulated TGF‐β expression mediates a reversible cell cycle arrest

The ability to regulate the proliferation of normal cells in a reversible manner would be a useful adjunct to some clinical therapies. including many types of cancer chemotherapy and surgery for periodontal regeneration. While the application of recombinant growth factors and cytokines to target cells is a logical approach to regulate cell proliferation, the high turnover rates of these peptide factors often make this approach impractical. Recombinant adenoviral vectors can be used to direct the expression of transgene products such as growth factors in many cell types in vitro and in vivo. We have adapted the tetracycline-regulated expression system to allow regulated transforming growth factor (TGF)-beta1 expression using recombinant adenovirus. We demonstrate that infection with a recombinant TGF-beta-encoding virus system in primary human oral keratinocytes and in a lung epithelial cell line is sufficient to allow a cell cycle arrest that is reversible upon tetracycline addition. This inhibition is efficient even after the infection of a minority of cells in a population. These results highlight the possibility of using low level infection with recombinant adenovirus to cause short-term blocks on cell proliferation.

Tropisetron (Navoban) in the prevention of chemotherapy-induced nausea and vomiting ? the Nordic experience

An open, noncomparative, Nordic multicenter study was carried out during 1991-1992 to evaluate the 5-HT3 receptor antagonist tropisetron (Navoban) as an antiemetic agent for various types of cancer chemotherapy. A total of 630 patients were recruited from 15 centers in Sweden, Denmark, and Finland. Gynecological cancers (60%), breast cancer (15%), and lung cancer (10%) were the main diagnoses. Prior experience of chemotherapy was documented in 338 patients (54%). In 260 patients (41%), cisplatin was part of the cytostatic regimen. Carboplatin (23%), doxorubicin (27%), and epidoxorubicin (24%) were also frequently included. In all, 23 cytostatic agents were used in various combinations. The mean number of courses studied was 4.6 (range 1-19). Altogether, 394 of 619 evaluable patients (64%) were completely protected from acute nausea and vomiting during the first course of chemotherapy. Delayed nausea and vomiting were completely prevented in 45%-73% (days 2-6) in the complete series. Treatment efficacy remained stable (60%-79%) during ten consecutive courses of chemotherapy. With noncisplatin regimens, complete protection from acute nausea and vomiting was achieved in 72% compared with 52% for cisplatin regimens (P < 0.0001). Patients without prior experience of chemotherapy had higher control rates of acute nausea and vomiting (72%) compared to patients treated before (57%) during the first course, but not later on. There were no differences in delayed nausea and vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)

Tropisetron in the prevention of chemotherapy-induced nausea and vomiting: The Nordic experience

An open, non-comparative, Nordic multicenter study was performed during 1991-1992 to evaluate the new 5-HT3 receptor antagonist tropisetron, as an antiemetic agent in various types of cancer chemotherapy. More than 600 patients were recruited from 16 cancer centers in Sweden, Finland and Denmark. In this report an interim analysis on 231 patients is presented. Gynecological cancers (61%), lung cancer (14%) and breast cancer (7%), were the main diagnoses. In 118 of 231 patients (51%) prior experience of chemotherapy was documented. In 91 patients (39%) cisplatin was part of the cytostatic regimen. Carboplatin (27%), doxorubicin (32%), epidoxorubicin (18%) were also frequently included. In all, 18 cytostatic agents were studied. The median number of courses studied was 3.3 (range 1-15). Overall 153 of 231 patients (67%) were completely protected from acute nausea and vomiting during the first course of chemotherapy. Delayed nausea and vomiting (Days 2-6) were completely controlled in 45%-72%. Treatment efficacy remained stable (57%-89%) over 10 consecutive courses of chemotherapy. For non-cisplatin regimens complete protection was achieved in 78% compared with 51% for cisplatin-regimens (p < 0.0001). Patients with no prior experience of chemotherapy had greater control of acute nausea and vomiting (73%) than patients treated before (61%) in the first course, but not in subsequent courses. There were no such differences in control of delayed nausea and vomiting between chemotherapy-naive and previously treated patients. Sex and age were significant prognostic factors with regard to antiemetic response. Adverse events were recorded in 19%-36% of the cases during long-term follow-up. Headache (16%) and constipation (5%) were most frequent.(ABSTRACT TRUNCATED AT 250 WORDS)

Pelvic vascular bed isolation in the management of radioresistant pelvic cancer

The term “pelvic vascular bed isolation” is given to our newly described type of cancer chemotherapy. The tissues underlying the bilateral vaginal mucosa are clamped for 4–6 hr. The hypogastric, superior gluteal, inferior gluteal, internal pudendal, obturator and ovarian arteries and veins are all ligated. MMC solution ranging from 50 to 80 mg is given into the hypogastric arteries. Pelvic isolation seldom caused prohibitive complications because the lumbar artery served as a collateral shunt by making its own way into the median sacral artery. We reported here controlling recurrent cervical cancer for about one and a half year in one case, and panhysterectomized radioresistant pelvic cancer for at least 3 mo in two cases with this type of cancer chemotherapy. Clinical benefit to these patients was also great.