Clostridial Spores for Cancer Therapy

Solid tumor accounts for 90% of all cancers. The current treatment approach for most solid tumors is surgery; however it is limited to early stage tumors. Other treatment options such as chemotherapy and radiotherapy are non-selective, thus causing damage to both healthy and cancerous tissue.

Recent research has shifted towards understanding the tumor microenvironment and it's differences from that of healthy cells/tissues in the body and then to exploit these differences for treatment of the tumor. One such approach is utilizing anaerobic bacteria. Several strains of bacteria have been shown to selectively colonize in solid tumors, making them valuable tools for selective tumor targeting and destruction.

Clostridium-based cancer therapy is a promising approach for the treatment of solid tumours. Bacterial-based cancer therapy using Clostridium spp. offers a selective advantage in overcoming the obstacles of hypoxia and necrosis. Clostridium spp., being strictly anaerobic will only colonize in areas devoid of oxygen, and when systematically injected, spores germinate and multiply in the hypoxic/necrotic areas of solid tumors. Clostridium, although anaerobic, possesses the ability to sporulate, allowing them to remain dormant in environments where oxygen is present. However, when growth conditions are suitable (i.e., in the hypoxic/necrotic milieu of solid tumors), the Clostridium spores germinate and begin to colonize these areas. This aspect of Clostridium growth is being exploited for use in a number of various novel cancer treatment strategies currently being developed which utilize Clostridium as a vector to deliver therapeutics directly to the solid tumor site. Clostridial vectors can be safely administered as spores, and their efficacy in delivering and secreting therapeutic proteins has been demonstrated in a number of preclinical trials.

Clostridium spp. with spore formation.

Necrotizing fasciitis-a newly recognized complication of laryngectomy

Necrotizing fasciitis (NF) was recently recognized as a new post surgical complication of laryngectomy. NF is an unusual, life threatening, rapidly advancing serious infection characterized by widespread fascial and subcutaneous tissue necrosis and gangrene of the skin. It most commonly affects the extremities, abdominal wall and perineum, whereas cervical NF is rare. NF of the head and neck is often caused by both aerobic and anaerobic microorganisms found in the upper aerodigestive tract. Usually, cervical NF originates from odontogenic, tonsillar and pharyngeal infection, and it is very rarely a complication of surgical procedure. Without immediate surgical treatment, cervical NF leads to mediastinitis and fatal sepsis. There was only one case of cervical NF after total laryngectomy described in the literature. Hadzibegovic and colleagues recently reported two additional cases of cervical NF after total laryngectomy, selective neck dissection and primary vocal prosthesis insertion. In both cases, the infection spread to thoracic region and in one of the patients NF was associated with Lemierre's syndrome ( thrombosis of the internal jugular vein). In both patients, vocal prosthesis was inserted during the infection and did not influence the healing process.

CT scan of the neck demonstrates gas in the soft tissue of the left side of the neck associated with necrotizing fasciitis.

Individuals with oral cancer are colonized with greater number of bacteria and yeast

Changes in the microbial flora on the oral mucosa after cancerous alteration may lead to both local and systemic infections. Researchers from India assessed the microbial flora associated with the surfaces of oral squamous cell carcinoma and compared the oral microbial contents with healthy mucosa. They also assessed the microbial flora from the saliva culture in subjects with oral squamous cell carcinoma and healthy controls.

The study included 30 subjects with oral squamous cell carcinoma and 30 healthy matched controls. The investigators found that oral squamous cell carcinoma sites harbor significantly more bacteria and yeasts compared to the control group. The microbial flora predominantly isolated from the carcinoma site were Streptococcus, Staphylococcus, Moraxella, Klebsiella, Citrobacter, Proteus, and Pseudomonas spp., Enterococcus feacalis, and Candida albicans. The median number of colony forming units (CFU)/mL at carcinoma sites (3.85 x 105 CFU/mL) was significantly higher than that of the healthy mucosa (0.571 x 105 CFU/mL) Similarly, in saliva of carcinoma subjects, the median number of CFU/mL (2.408 x 105 CFU/mL) was significantly higher than that of saliva in control subjects (0.78 x 105 CFU/mL)  

The study clearly indicates that the subjects with oral squamous cell carcinoma harbor significantly more microbial flora. The study's implications are that emphasis has to be made to prevent changes in the microbial flora of the oral cavity. This can be achieved by reducing sugar intake, using probiotics when indicated, avoiding unnecessary use of antibiotics, and maintaining good dental and oral hygiene. 

Microscopic view of oral bacteria and yeast 

Antibiotics treatment can be as effective as surgery for appendicitis

A meta-analysis published in the British Medical Journal of four randomised controlled trials including 900 adult patients ( > 18 years ) compared antibiotic treatment and appendicectomy for uncomplicated acute appendicitis showed that antibiotics can be used safely as primary treatment in patients presenting with acute uncomplicated appendicitis. Antibiotic treatment was not associated with an increased perforation rate compared with surgery, nor were any significant differences seen in the length of stay or treatment efficacy between antibiotics and appendicectomy. Antibiotic treatment was associated with a 63% success rate and a reduced risk of complications. About 20% of patients who were treated with antibiotics had appendicectomy for recurrence of symptoms, and of these only about one in five had complicated appendicitis. 

The authors concluded that an early trial of antibiotics may merit consideration as the initial treatment option for uncomplicated appendicitis. They suggested that the possibility that perforated and non-perforated appendicitis could have different patterns and pathological processes needs further evaluation. Future studies may show if uncomplicated acute appendicitis should be treated in a similar fashion as other conditions such as acute colonic diverticulitis in which antibiotic treatment plays an important role.

Effects of exposure to smoking on the aerobic and anaerobic microbial flora of children and their parents

Several studies investigated the effects of exposure to direct and indirect smoking on the oro-pharyngeal colonization with potential pathogenic bacteria and aerobic and anaerobic organisms that can interfere with their growth. The potential pathogens included Streptococcus pneumoniae, Hamophillus influenzae, Staphylococcus aureus , and Streptococcus pyogenes. Bacteria with interference capability of potential respiratory pathogens include alpha- hemolytic streptococci, non-hemolytic streptococci, and Prevotella and Peptostreptococcus spp.

The flora of smokers contained less aerobic and anaerobic organisms with interfering capability and more potential pathogens as compared with non-smokers. The high number of pathogens and the low number of interfering organisms found in the nasopharynx of smokers revert to normal levels after complete cessation of smoking.

A high recovery rate of potential pathogens and low number of interfering organisms were observed in otitis media prone (OMP) children. This was not related to their parents smoking habits. The flora of smoking parents contains more potential pathogens that are similar to the one recovered from their OMP children, and less interfering organisms as compared to non-smoking parents.

Parents that smoked were more often colonized by potential pathogens than parents that did not smoke. The flora of healthy children of smoking parents contained high number of potential pathogens similar to the one found in their parents and OMP children. Concordance with pathogens in the parent was high among the OMP children of smoking parents but this was not observed in OMP children of non-smoking parents. A higher recovery rate of potential pathogenic organisms was observed in OMP children of both smoking and non-smoking parents, as compared to healthy children whose parents were non-smoking. Since smoking parents harbor more potential pathogens and less interfering organisms they may serve as a source of pathogens that can colonize and/or infect their children.

These studies illustrate the adverse effects of direct and indirect exposure to smoking on colonization with potential bacterial pathogens