Latest Research 2024

Period From 1/2024 through 6/2024

The group held a conference calls  on March 1 and April 26. The next conference call is scheduled for June 14, 2024.

March 1: Ms. Nieciecki presented several Powerpoint slides that covered new microbiome results that she has recently gotten. Ms. Nieciecki mentioned that the meta data provide by Mercy had been very useful for her analysis. One slide discussed the core PMP microbiome at the genus level that she has found. Included in the core genus microbiome were: Staphylococcus, Pseudomonas, Acinetobacter, Streptococcus, and Corynebacterium. Ms. Nieciecki found that the bacteria in PMP tumors clustered into two groups, independent of metadata. One cluster was higher in Bacteroides, and the other cluster was higher in Staphylococcus, Pseudomonas, and Acinetobacter. Finally, Ms. Nieciecki’s results showed that patients who had received prior chemotherapy had a less diverse tumor microbiome than those who had not received chemotherapy. Ms. Nieciecki did not have information on whether the patients had received antibiotics. She will incorporate her new results into the paper she is working on. A lengthy discussion of Ms. Nieciecki’s results took place. Dr. Merrell suggested that that it might be good to look at patient overall survival.

Dr. McAvoy mentioned the recent paper that he had found on  DNA testing of 15 PMP patients.The paper title is:Genome-wide analysis of DNA methylation in pseudomyxoma peritonei originated from appendiceal neoplasms. https://pubmed.ncbi.nlm.nih.gov/38262376/This paper is the first report of comprehensive DNA methylation profiles of PMP patients in the world. The paper indicated that genes associated with neuronal development and synaptic signaling may be involved in the development of PMP. Dr. Metcalf suggested that the neurons and synapses probably were in the peritoneal region and not the brain. Their change could lead to a suppressed immune system. After the conference call Dr. McAvoy found that the supplementary data from the paper had been published, but not the paper itself.

April 26: Dr. Li presented several Powerpoint slides that covered his research on compounds that he has isolated from PMP cell line cultures. The slides showed the apoptosis activity that two of the compounds have against PMP cell lines. Their activity is comparable to that of mitomycin C which is used in heated chemotherapy treatment for PMP. The compounds also have activity against other types of cancer cell lines including colon cancer and breast cancer. The compounds did not show activity against normal cell lines. Additional compound analogs have been isolated by Dr. Li and they will be studied by him. Dr. Merrell raised the issue of performing Synergy Assays to see if the novel compounds show synergistic interaction with mitomycin C and other cancer-related drugs. An extended discussion took place about Dr. Li’s presentation and the culturing of PMP cells from tumors.

Dr. Metcalf discussed the manuscript on our latest microbiome research. The paper will be submitted and she recommended Cell, Host, and Microbe as the journal for submission. Dr. Metcalf felt that our results have broader implications than for PMP itself and that Cell, Host, and Microbe would reach a broader audience of readers. A discussion then took place about the paper that Dr. McAvoy had emailed to the group prior to the conference call. This paper, which is different from the paper mentioned in the March 1  summary above, discussed microbiome findings on mucin taken from PMP patients. The most prevalent species that was found was Pseudomonas plecoglossicida (~20%). Several questions were raised by the group about this finding. After the conference call Dr. Merrell clarified that the author’s approach sequenced on the order of 450-500 base pairs from the 16S gene, which has about 1600 base pairs. To get fully accurate species identification, you typically need to sequence the full-length gene. Our group was trying to point out that getting a species level identification is very difficult with the type of approach discussed in the paper. Thus, the author’s report of a specific bacterium that has not been found by others in the human microbiome can be questioned. In addition, the quality of the journal in which the paper was published was questioned. As a result of the discussion, the group felt that the results in the paper were questionable. Dr. Li raised the issue of sequencing the entire genome of bacteria obtained from PMP tumors. Ms. Nieciecki pointed out that typically the samples she has analyzed have had low biomass. For whole genome sequencing to be successful, a tumor specimen with a lot of biomass should be studied. Ms. Nieciecki mentioned that one of her samples did contain significant biomass and Dr. Li might want to consider it.